Myths and Realities about the Private Sector Stem Cell Industry in Malaysia

Abstract

Notwithstanding its potential medical benefits, there are unproven stem cell–based therapies being offered across the globe. Little is known about the landscape of Malaysia’s private stem cell sector of which this study aims to explore. Qualitative study was conducted to explore its status through empirical interviews with stakeholders in the private sector. This study reveals that private researchers face with limited funding and overwhelming bureaucracies resulting in a low output. There is also a lack of governance for stem cell therapy, and some concerns over how stem cell–based therapies are being offered. Hence, urgent interventions by regulatory authorities are vital to ensure ethical and safe clinical practices in the private sector to protect the reputation of this promising industry.

Introduction

Stem cells have a tremendous therapeutic potential to treat various diseases. There are nearly 8000 stem cell clinical trials conducted worldwide, with the numbers increasing annually. The majority of these trials aim to treat osteoarthritis (Glyn-Jones et al. 2015; Mat et al. 2019; Zhu et al. 2017), to replace damaged retina cells (Öner 2018; Rathod et al. 2019), to alleviate chronic metabolic diseases such as diabetes (Zhang et al. 2020), and to benefit Alzheimer’s and Parkinson’s disease patients (Fleifel et al. 2018; Haenseler et al. 2017). Stem cells can also be used as immunosuppressors and immunomodulators and such applications have been observed in treating immune-mediated diseases such as inflammatory bowel disease (Baer et al. 2019; Shimizu et al. 2019). However, most of these potential therapies remain under clinical evaluation (Jevotovsky et al. 2018; Wyles et al. 2015). In addition, apart from the first sanctioned stem cell–based therapies for haematological disorders using haematopoietic stem cells (HSCs) (FDA 2019), many countries have approved the use of cultivated limbal epithelial transplantation (CLET) and cultivated oral mucosal epithelial transplantation (COMET) to address ocular surface diseases (Cabral et al. 2020; Oie et al. 2021; Singh et al. 2021). For example, Holoclar® from Chiesi Pharma in Italy offers an official service for these therapies across Europe (Pellegrini et al. 2016).

Globally, the private sector plays a significant role in driving the commercialisation of stem cell–based therapies, with established markets in countries such as the USA, South Korea, and Singapore. In the USA, the FDA has set clear guidelines for the clinical use of stem cells, which has led to the commercialisation of approved therapies, such as haematopoietic stem cell transplants for blood disorders (FDA 2019; Sugarman et al. 2018). Notwithstanding this promising development at the global level, stem cell technology is surrounded by contentious issues, and among them is the marketing of unproven stem cell therapies or products (Sipp et al. 2017). It has been widely reported that numerous fraudulent stem cell providers worldwide are offering unproven stem cell therapies and falsely advertise these ‘therapies’ as ‘cure-alls’ without providing evidence of efficacy (Master et al. 2021; Turner and Snyder 2021; Waldby et al. 2020). Unfortunately, the private sector also contributed to the concerns regarding the increasing of unregulated markets for unproven therapies. For instance, a study in 2015 reported that 17 private clinics and 3 stem cell companies in Australia were identified for providing autologous adult stem cell therapies for a wide range of diseases outside clinical trials and the medical practitioners who provided these therapies in those private clinics are not involved in the provision of care (McLean et al. 2015). In recent years, after the emergence of the COVID-19 pandemic, some private businesses are even offering unproven stem cell therapy to treat COVID-19 patients (Turner 2020). Many safety-related incidents and adverse effects have been reported due to unproven stem cell therapies, which include chronic pain, permanent disabilities, severe infections due to the contaminated stem cell products, and even deaths (Bauer et al. 2018; Cyranoski 2010; Lysaght et al. 2017; Tuffs 2010; Turner and Snyder 2021).

As with many other countries, Malaysia also recognises stem cell technology as a critical economic driver (Bt Hj Idrus et al. 2015). The country is a host of research institutions and stem cell therapy providers. According to an advisory report produced by the Academy of Sciences Malaysia, the number of stem cell researchers is only about 110 researchers. The researchers are affiliated with public universities (Universiti Malaya, Universiti Kebangsaan Malaysia, Universiti Putra Malaysia, Universiti Sains Malaysia, Universiti Teknologi Mara); private universities (International Medical University, Universiti Tunku Abdul Rahman, International Islamic University, Nottingham University, Monash University); the Institute of Medical Research, which is a public research institution; and an international entity (Stempeutics) based in the country (Academy of Science Malaysia 2013). However, this report was produced in 2012, and the number of researchers might have changed after a decade. As for the therapy, there is no official document or a single database that can be referred to, and the advisory report does not provide an overview of the ecosystem for cell therapies. Nonetheless, there are many private clinics in Malaysia that offer stem cell therapies for regenerative and aesthetic purposes, from improving mobility to restoring skin conditions. The commonly used stem cells include haematopoietic stem cells and mesenchymal stem cells (Imran et al. 2022). In 2012, it was widely reported that a national Olympic athlete recovered from an ankle injury just in time to compete with the help of stem cell injections even though this therapy was not proven for its efficacy and safety at the time of administration (Ung 2012). To have a general idea as to how many private clinics that offer stem cell ‘therapies’ in the country, a simple Google search was carried out, and the result may suggest that stem cell industry in the private sector is quite flourishing. However, this search may not be accurate, and more thorough research is needed. Be that as it may, little is known about its development and whether the ‘therapies’ offered are being carried out in an ethical manner.

The Private Healthcare Facilities and Services 1998 and Regulations 2006 only regulate the setting up of healthcare facilities including hospitals and clinics in Malaysia. The scope of the Act includes licensing requirements to ensure minimum acceptable standards are met in terms of safety and quality of the facilities and services and the accountability of licensees to ensure the hospitals and services are maintained or operated by a registered medical practitioner. The Act does not specifically regulate the types of therapy provided by licensees. Therefore, it can be argued that stem cell therapy is not being regulated by the existing legislation. Despite the absence of legislation for this area, Malaysia has established national guidelines for stem cell research and therapy in 2006, and they were updated in 2009 (MOH 2009). In addition, the Guidance Document and Guidelines for Registration of Cell and Gene Therapy Products (CGTPs) in Malaysia was developed by the Technical Working Group (TWG-CGTPs), chaired by the National Pharmaceutical Control Bureau (NPCB), Ministry of Health of Malaysia. It was widely adopted since January 2016 and served as the main reference for the stem cell industry in Malaysia with the hope that the regulation of CGTPs supports good science, increasing and monitoring safety and enhancing data reliability (Loh et al. 2021). Nonetheless, there is no oversight mechanism targeting unproven therapy in the country.

A previous study by Bin Abdul Aziz et al. (2022) had shown that the existing regulation of this field in Malaysia is rather ineffective in facilitating this technology to be further developed in an ethical fashion due to its complexity. In addition, Nisha et al. argued that unethical conducts are most likely present in the private stem cell industry in comparison to the public sector because research and therapeutic activities in the public university and research institutions are closely monitored by the institutional review board or ethics committee and the relevant authorities through the national guidelines such as the National Pharmaceutical Regulatory Agency (NPRA) and National Medical Research Registry (NMRR) (Gopalan et al. 2020). However, the status of research and therapeutic activities in the private sector is not known. This has caused some local stakeholders to express their concern about the private sector, disapproving some of their claims for being unethical and harmful to public safety. This was also reported in another study by Bin Abdul Aziz et al. (2018), and it was argued that if this situation is not addressed appropriately, it would put the reputation of this field in the country at risk. Given the situation, we set out to capture the current status of stem cell development and the perspectives of the stakeholders in the private sector through empirical interviews. Nonetheless, it is worth noting that this study does not specifically target to interview providers of unproven stem cell therapies.

Methodology

The first author undertook qualitative interviews with key stakeholders within Malaysia’s private stem cell sector. A systematic online search was conducted using major search engines, primarily Google, to identify relevant private stem cell entities (both company or clinics that provide stem cell ‘therapies’ and institution that carry out research activities) in Malaysia. To optimise this search, the following terms were utilised: ‘stem cell (research OR therapy) AND Malaysia’. The top 20 pages of search results show a list of 800 entities, and they were meticulously analysed. Each company’s or institution’s website was scrutinised in depth, with a focus on profiles to determine their registration status in relation to stem cell research and therapy. The portfolios (whether the entity carry out stem cell research and/or offer stem cell ‘therapies’) of the identified companies or institutions were further validated via telephone inquiries. The first author then requested each company and institution that agree to be involved in this study to name or recommend a potential respondent.

Interview respondents were selected based on specific eligibility criteria. Only private entities actively engaged in stem cell research and therapy and duly registered under the Private Healthcare Facilities and Services Act 1998 were considered. Retail entities primarily marketing stem cell–derived products, such as plant-based stem cell products, were excluded. The underlying rationale is the assumption that individuals from legally registered or licensed institutions would naturally be more amenable to take part in the interviews and more capable of providing genuine and informed perspectives on the current system. In addition, this study does not investigate whether the respondents provide unproven stem cell therapies, but to only capture their perspectives as to how stem cell ‘therapies’ are being developed and offered in the private sector. Following a meticulous selection process, 18 potential respondents from distinct private companies and institutions were shortlisted. Initial outreach was via e-mail and followed by a formal letter of invitation. Of those approached, all responded, but only 14 were available for the interview. The respondents, recommended by their respective companies or institutions, hailed from varied backgrounds, encompassing physicians, academics, company directors (with one also serving as a physician), production scientists, and research scientists.

This study adopted both in-depth and semi-structured interviewing methods, as advocated by Gill et al. (2008) in order to extract rich data from the respondents. The interview guide comprised several open-ended questions delving into the participants’ experiences, with a specific focus on the development and application of stem cells in the private sector. Moreover, the interview guide was structured to assess the awareness and understanding of the participants concerning local guidelines related to stem cell research and therapy and ethical considerations in providing stem cell–based therapy. Additionally, the guide also contains sections that are dedicated to gauging participants’ familiarity with various regulatory and review bodies. Each interview was conducted face-to-face on a one-to-one basis, with durations typically ranging from 30 to 60 min. Detailed verbatim transcripts of these sessions were produced post-interview. To foster a genuine and uninhibited response from the respondents, measures were taken to ensure their anonymity. This entailed obscuring both their personal details and any identifiable company information. Each respondent was provided with a participation information sheet and an informed consent form to indicate their consent for both participation and audio recording. Ethics approval was duly obtained from the Universiti Malaya Research Ethics Committee prior to the commencement of the study, with the approval reference: UM.TNC2.UMREC-785.

In terms of our analytical approach, we used thematic analysis facilitated by ATLAS.ti 8.0 software (ATLAS.ti Scientific Software Development GmbH) to identify and examine emerging themes and patterns within the transcripts. This involved initial coding, followed by categorising and clustering codes to form overarching themes. Throughout this analytical process, there were continuous discussions among the research team to ensure the reliability and validity of the identified themes. This analytical process was completed by both researchers.

The following steps were involved in the thematic analysis:

1. Familiarisation with the data: After conducting the interviews, all interviews were transcribed verbatim. The first step in the analysis involved reading through the transcripts several times to become familiar with the content. The researchers also listened to the audio recordings to ensure accuracy and completeness in the transcriptions.

2. Initial coding: After familiarisation, initial coding was conducted using ATLAS.ti 8.0 software, which helped organise and manage the large volume of qualitative data. Each transcript was systematically reviewed, and relevant data segments were highlighted and coded. Codes represented recurring ideas or issues raised by the participants, such as regulatory challenges, ethical concerns, or financial constraints.

3. Generating initial themes: Once the data were coded, the next step involved grouping the codes into potential themes. Themes represent broader patterns of meaning across the dataset. For instance, codes relating to funding challenges and lack of research infrastructure were grouped under the theme ‘Financial and Infrastructural Barriers to Innovation’. Similarly, codes about ambiguous regulations and lack of regulatory enforcement were grouped under the theme ‘Regulatory Challenges’.

4. Reviewing and refining themes: The initial themes were reviewed by the research team to ensure that they accurately represented the data. At this stage, some themes were merged or refined to better capture the essence of the data. For example, the theme ‘Ethical Challenges in Offering Unproven Therapies’ was developed to capture both the lack of regulatory oversight and the ethical concerns about offering unproven stem cell treatments to patients.

5. Defining and naming themes: The final themes were clearly defined, and names were assigned that succinctly captured their essence. The main themes identified included ‘Regulatory and Ethical Gaps’, ‘Financial and Infrastructural Barriers to Research’, and ‘Private Sector Dynamics and Market Pressures’. These themes formed the basis for the subsequent reporting of the study’s findings.

6. Writing up the analysis: Once the themes were finalised, a detailed narrative was written, weaving together the themes and supporting them with quotes from the interview transcripts. The thematic analysis allowed the researchers to draw connections between the experiences of different stakeholders and to provide insights into the broader landscape of the private stem cell industry in Malaysia.

Reflexivity statement: We acknowledge the potential biases and preconceptions we, as researchers, might bring to this study. Throughout the analysis, we endeavoured to remain self-aware and reflexive, continuously challenging our interpretations to ensure that they were rooted in the participants’ perspectives rather than our own assumptions or beliefs.

Findings

We report the findings of the interviews in two parts: first, the current landscape of stem cell research and therapy in the private sector in Malaysia; and second, the respondents’ perspectives of the ethical challenges and concerns over the practice of offering stem cell therapy in Malaysia.

Current Landscape of Stem Cell Research and Therapy in the Private Sector

Development of Research and Therapies

There are stem cell therapies being offered for many types of diseases and conditions in Malaysia; however, we only captured research developing therapies for cardiovascular diseases, neurological disorders, degenerative diseases, osteoarthritis, cornea regeneration, and aesthetic purposes. For example, a respondent shared that they have been developing a non-invasive therapy for cornea disease using stem cells. The procedure involves sampling stem cells from the patient’s eye and culturing them onto a biodegradable contact lens. After the cells mature, the lenses are then placed onto the patient’s eyes allowing the stem cells to migrate and grow, regenerating the damaged cornea. However, this project remains a work in progress.

As for now, the [anonymous] institution collaborates with our team to develop a technique where we can use your own stem cell or cell from your eye to culture on a Japan-made contact lens. Then, the patients who have their damaged cornea to be removed and stitched with this special lens. After three to four months, it will regenerate itself… — Respondent 2 (Company Director and Physician).

Stem cell research is a rapidly advancing field in Malaysia, with a focus on developing innovative solutions for prevalent medical conditions that offer potential commercial value. As highlighted by respondents 8 and 14, cardiovascular diseases, a leading cause of mortality in the country, are an area where stem cell research is demonstrating significant potential. Additionally, there is noteworthy advancement in stem cell–based therapies targeting neurological disorders, such as Alzheimer’s and Parkinson’s diseases, which are on the rise due to an ageing population. According to respondent 14, there is also a growing emphasis on the development of stem cell therapies for autoimmune diseases, which affect a significant portion of the Malaysian population.

Our organisation is focusing on researching the potential of stem cells to treat a wide range of diseases and medical conditions. We are particularly interested in developing stem cell therapies for cardiovascular diseases, neurological disorders, and autoimmune diseases… — Respondent 8 (Research Scientist).

We have recently focused on researching stem cell solutions on autoimmune diseases and cardiovascular disorders… — Respondent 14 (Researcher).

Some of the private businesses have heavily invested in exploring the therapeutic potentials of reverse ageing therapies. Respondent 2 and respondent 6 emphasised that they believe the cytokines and chemokines of stem cells can improve skin healing for conditions such as lesions or scars. Fuelled by a growing consumer interest in anti-ageing cosmetics, these private entities have shown tremendous interest in capitalising on the uses of stem cell exosomes. Respondent 2 also shared that his company extracts such exosomes for exportation to Korea or China, where these exosomes will be used to produce cosmetic products such as serums or facial masks. Additionally, as mentioned by respondent 11, the application of stem cell–based therapies in cosmetic procedures is becoming increasingly prevalent. One notable example is the utilisation of adipose-derived stem cells for facial rejuvenation therapies.

We do offer the patients some stem cell exosome-based products that contain the ingredients that can heal facial scars and tissue lesions. Mainly from Korea or China, our cosmetic products are made up of these stem cell exosomes… — Respondent 2 (Company Director and Physician).

Yes, I know there are cytokines and chemokines that have great potential in the healing process, and we see great improvement among our clients using our exosome products — Respondent 6 (Physician).

Our stem cell-based treatments are used to enhance the appearance of our patients by promoting natural collagen production, reducing wrinkles, and improving skin texture and tone — Respondent 11 (Physician).

Lack of Funding

Some respondents shared a concern that their research progress is relatively slow compared to their counterparts in the public sector. Respondents 3 and 9, who are the private university researchers, stressed that it is difficult to obtain funding given that private institutions do not have substantial access to governmental grants. Private universities need to heavily rely on tuition fees to drive their research activities. Given stem cell–based research is expensive and requires well-equipped laboratories, they stated that many private institutions need to collaborate with well-equipped public universities and research institutions.

I need to collaborate with them as they can afford to buy this machine for our exosome research. I also need to approach this institution in order to use some of their equipment, — So, the regular problem that I face definitely is the financial support because we are from aprivate institution — Respondent 3 (Researcher).

We have several translational projects in progress. However, we received very little financial support from our organisation and struggle a lot to secure huge research funds as most of these fundings go to public domain. Our projects halted several times due to this financial foe and hence we are keen to work with the public research entities to keep our project “alive” — Respondent 9 (Researcher).

Lack of Expertise and Infrastructure

Private stem cell businesses are also facing some challenges. They lack human resources and infrastructures that are needed for research and development activities. According to respondent 2, diverse expertise is needed to ensure translational work, even for the development of stem cell–based cosmetic products. It was also stated that the lack of relevant experts would disrupt research work and eventually halt the intended product commercialisation. As a result, many private businesses struggle to innovate.

I know that in order to make an exosome formulated serum, I require a mathematician, pharmacist, nanotechnologist, chemist, aesthetic doctor and dermatologist, and biomedical engineer. I need so many experts to develop one product only for cosmetic use — Respondent 2 (Company Director and Physician).

In addition, according to respondent 5, only some of the private stem cell businesses in Malaysia have Current Good Manufacturing Practices (cGMP)–compliant laboratories.

We currently have more than twenty facilities in the private sector giving stem cell therapies, but not all of them comply with thecGMP requirements because it is not strictly enforced at the moment… — Respondent 5 (Research Scientist).

It would be easier for us to collaborate with the research institution with GMP lab by providing them some research grants… — Respondent 2 (Company Director).

Given the situation, they need to collaborate with local or international universities, which have the facilities and infrastructure that comply with cGMP. In return, they would offer research grants to the collaborating universities. This approach is perceived as an alternative to overcome the limitations. Respondent 2 further argued that this approach is economically feasible for private businesses to be involved in research work, patent development, and research publication without needing a laboratory.

Lax Regulation

Most respondents stated that they adopt guidelines established by foreign countries instead of the local guidelines. For instance, respondents 2 and 5 shared that their company would refer to regulations and standards of other countries such as the US and Australia.

Yes, we are aware of FDA guidelines, and we always stick to these guidance documents… — Respondent 2 (Company Director and Physician).

I do not really remember about the local guidelines, but we are adopting the Australian standard so far — Respondent 5 (Research Scientist).

Many find the local guidelines convoluting and ambiguous. They also pointed out that local governing bodies failed to provide concise information on regulatory matters when enquired. For instance, respondents 2 and 14 shared their experiences dealing with a local governing body, whereby a relevant official gave conflicting information regarding the registrations of stem cell–based products, and this has caused a delay in research progress. The official also suggested that the guideline acts only as a reference, which gives the impression that it is not particularly important.

We completed this OA (Osteoarthritis) clinical trial five years ago, yet the product is still unregistered because we faced a lot of challenges while applying for registration. There was an officer who said the guideline is only for reference and registration is not compulsory — Respondent 2 (Company Director and Physician).

We are not well informed about the current regulations, NPRA only said guidelines are available as references. Such ambiguity in regulations and governance can add additional challenges to ensure compliance and ethics — Respondent 14 (Private researcher).

Ethical Challenges and Concerns over Stem Cell Therapy

Exorbitant Fees for Unproven Stem Cell Therapy

In Malaysia, many of the stem cell therapies being offered remain experimental. However, patients are still being charged. Respondent 4 shared a concern over this current scenario whereby patients are charged with a large amount of fees a ‘therapy’ that is not yet proven.

I feel uneasy because patients need to pay such an expensive bill but we have not verified whether these stem cells can really improve their conditions for a long run — Respondent 4 (Research Scientist).

Another respondent who shared a similar sentiment about the exorbitant fees for unproven therapy argued that this raises the issue of accessibility. It was argued that this issue needs to be addressed because the exorbitant cost will put some people who are less fortunate financially at a disadvantage and unable to benefit from the therapy that they need.

I personally feel that stem cell therapy is currently affordable by the rich ones for the high expenses incurred. I think some sort of effortis needed to make it available for more people who may need it especially when it comes to therapeutic purposes — Respondent 5 (Research Scientist).

On the contrary, another respondent who is a physician at a private clinic supported high pricing for stem cell–based therapies. According to the respondent, Malaysia’s current pricing is justifiable because the materials used for stem cell extraction, for instance, in treating patients with osteoarthritis, are expensive, and it involves laborious procedures.

I think it is reasonable to charge these prices because the preparation of stem cell therapy requires massive work — Respondent 13 (Physician).

Informed Consent

The practice of ‘informed consent’ was highlighted during the interviews. Based on the account shared by respondents 5 and 10, when obtaining consent, stem cell providers may leverage on their published research work and other publications to convince patients to agree to a therapy.

Before they agreed and signed the consent, we [stem cell provider] always show the clients what we have done, for examplesome journal papers that prove the effectiveness of stem cell therapies. It works most of the time to convince them to provide their consent… — Respondent 5 (Research Scientist).

It is always useful to showcase our research publications and news articles on newspaper or magazine. Patients and their families feel more comfortable to provide consent as they know we are genuinely helping them — Respondent 10 (Researcher).

However, respondent 5 shared a concern over a certain approach adopted by some stem cell providers who would leverage on the hype and the excitement over the unique ability of stem cells to regenerate into different types of cells and tissues when providing patients with information about a proposed stem cell–based therapy. It was argued that such a strategy is unacceptable.

It is not acceptable to say that stem cell therapy is a superior version of platelet-rich plasma (PRP) and convinced that the stem cell has the ability to regenerate into whatever cells we want to. This is what I heard when the doctor explained to the patient and her family before getting the consent — Respondent 5 (Research Scientist).

Another concern shared by another respondent is how some general practitioners would administer stem cell therapy for complex diseases without consulting specialised doctors. It was argued that most specialists would not agree to such an intervention given the lack of evidence.

I know a lot of people [general practitioners] do it [stem cell therapy for *] without consulting neurologists and most neurologists would not be there to do so because they don’t see big evidence… — Respondent 6 (Private Physician).

Also, there is an issue of how consent is obtained from elderly patients. Based on respondent 6’s experience, elderly patients would entrust decision-making to their doctors or next-of-kin.

The elderly patients seldom want to listen when we are explaining about stem cell therapy and usually rely on their children or doctors. They rely on what have been told and act accordingly because they trust their doctor and children — Respondent 6 (Private Physician).

Furthermore, respondent 2 shared that some donors who agreed to donate their umbilical cord are not informed of the potential commercial purposes, which indicates an ethically concerning practice. This suggests that there is an issue of transparency in procuring donated specimens from patients, which are then used as a source for stem cells.

They do not know this umbilical cord can be commercialised one day; we did not tell them… — Respondent 2 (Company Director and Physician).

Attractive Marketing Strategy and Commissions

Respondent 2 emphasised that local stem cell therapies or products available in Malaysia also have a strong presence overseas, attracting clients from other countries such as India, China, and Indonesia. Based on the findings, the stem cell providers would use different strategies in promoting stem cell therapies. For instance, according to respondent 1, a commercial activity can be further stimulated if celebrities are involved in the publicity agenda.

We have huge market from other Asian countries especially China, India and Indonesia where the patients can come easily and get their stem cell therapies here — Respondent 2 (Company Director and Physician).

We plan to have … (celebrity) to be our branding ambassador but we are still negotiating the costing. We believe it can further stimulate the present market — Respondent 1 (Production Scientist).

In addition, respondent 13 highlighted that numerous companies enhance the appeal of their stem cell therapies by bundling them with an array of enticing packages, thereby amplifying the value proposition for patients.

It is not easy to convince our patients because the treatment cost is not cheap and hence, we need to think about strategies to make it attractive to them. For example, we provide other health screening packages to make their treatment journey worthwhile — Respondent 13 (Physician).

Another strategy is also to leverage physicians. As shared by some of the respondents, lucrative commissions are offered by companies to physicians. According to respondents 2 and 7, physicians are the biggest beneficiaries after the company. Physicians who agree to perform these therapies may be rewarded at least RM 5000 for every therapy performed.

Yes, we do provide them a very attractive remuneration package, it’s five thousand Ringgit at least for a successful case, very irresistible… — Respondent 2 (Company Director and Physician).

I would say it’s a huge amount of money from stem cell business and it isn’t a complicated procedureto perform… — Respondent 7 (Physician).

Discussion

Unlike other published studies in the Malaysian context that primarily focus on the perspectives of stakeholders in the public stem cell industry (Bin Abdul Aziz et al. 2018; Bin Abdul Aziz et al. 2022; Gopalan 2024), this research offers insights into stem cell research and therapy from the viewpoint of stakeholders in the private sector. Through thematic analysis, three key issues have been identified: (i) research progress is hindered by funding and regulatory challenges, (ii) private businesses offering stem cell therapies are under-regulated, and (iii) there are significant risks of unethical conduct.

Hampered Research Progress due to Funding and Regulatory Issues

Based on the findings, a principal reason as to why researchers in private universities struggle to progress in research is due to the lack of funding. As reported above, unlike public universities, private universities or private research institutions do not have abundant access to government funding or research grants. Such a situation has also been reported previously, whereby private universities are struggling financially (Williams 2018). Therefore, the plausible way of addressing this issue would be to encourage collaboration not only between the public and private universities but also with private companies, which have the financial capability of funding research activities. This would be a win–win situation for private companies too because they need expertise and human resources for their research and development (R&D) activities as highlighted above.

However, it is worth noting that companies are also facing challenges in understanding the existing regulations. They find the current regulation as lacking clarity, and the regulatory system is complex, a similar argument that has been raised in a previous qualitative study in Malaysia that captures the opinions shared by researchers from the public sector (Bin Abdul Aziz et al. 2018). Even though private actors could address their lack of human resources and expertise issues through collaboration with public universities, the fact that they are uncertain of the regulation can be a stumbling block for their research advancement. As highlighted above, a single stem cell product registration would take many years. This suggests that there is a need to revisit the current regulatory system given it affects both the public and private actors. In particular, the revision of the national guidelines is urgently needed to address the issues of clarity and ambiguity. The guidelines are perceived as outdated since it was introduced in 2009, and no update has been made to the provisions; therefore, it can be argued that it is high time for a revision to take place (Bin Abdul Aziz et al. 2018). This is particularly vital to facilitate researchers and stem cell providers to progress.

In addition, our findings also show that there is a lack of awareness, understanding, and adherence to the existing national stem cell guidelines (MOH 2009). A similar finding was also reported in a study by Loh et al. (2021), whereby it reports that the awareness among industry players on the mandatory regulation of cell and gene therapy products was lower than expected despite the industry was given a 4-year gap before the implementation of the regulation. One possible solution would be to encourage private entities to join associations that are established to develop this field. Such organisations would allow stem cell stakeholders, both private and public, as well as the regulatory authorities to be well connected and enable better dissemination of information on regulations. There is an existing effort in Malaysia, for instance, the Malaysian Association for Cell Therapy (MACT) and Malaysia Society for Stem Cell Research and Therapy (MSCRT), which were established in 2012 and 2014, respectively. These are concerted efforts to bring researchers, regulatory authorities, individual scientists, and health professionals together to develop the cell therapy industry in the country. Another example of local stem cell–related networks is the Tissue Engineering and Regenerative Medicine Society of Malaysia (TESMA), which comprises mainly academicians and researchers from the public sector. The abovementioned societies play an important role in providing education and updates in the field of stem cells and tissue engineering through symposiums and conferences involving various stakeholders. In collaboration with the Ministry of Health Malaysia, these organisations can play a vital role to substantially bolster research integrity in the stem cell domain and the regulation of unvalidated therapies. Their combined efforts can yield a cohesive regulatory framework, uphold standardised research protocols, institute quality control benchmarks, inculcate ethical research methodologies, and protect consumers from unverified therapies.

Private Businesses offering Stem Cell Therapies are Under-Regulated

It appears that there is a lack of proper enforcement of the existing national guidelines. This is evident in the account shared by one of the respondents who noted that only a few facilities in the country offering stem cell therapies are cGMP certified. This raises concerns about how other facilities can provide these therapies without possessing the necessary certification, suggesting that the stem cell therapies or products available may not meet essential safety standards. Given the absence of standardisation in the private stem cell industry, consumers face challenges in evaluating the quality, safety, and potential efficacy of the stem cell products and services on offer. The issues surrounding Good Manufacturing Practices (GMP) certification are further aggravated by a lack of recognition regarding the importance of national guidelines and their enforcement. Two key situations, highlighted in the findings, underscore this problem. First, many respondents prefer to reference the regulations of countries such as Australia or the United States rather than adhering to local guidelines. This trend indicates that while there are documented reports regarding the proliferation of unproven stem cell markets in the private sector—implying that private actors are not observing regulations—there are also private stakeholders eager to operate within established and clear regulation. Their preference for foreign regulations stems from the perception that national guidelines are vague and problematic. As a result, they seek to align their innovative products with acceptable regulatory standards, ensuring their offerings can be successfully commercialised and recognised internationally. This situation signals to the relevant regulatory authorities that Malaysia could benefit from learning from other countries by adopting their well-established rules and adapting them to the local context, thereby promoting advancement in the private sector.

Secondly, the account shared by respondent 2 on how an official from a regulatory body suggested that the guideline is only a ‘reference’ could be an isolated case. However, it still raises a potential red flag given the importance of the existing national guidelines being downplayed. There needs to be a mechanism to facilitate effective and clear communication between regulatory authorities and stem cell stakeholders. This is essential to deliver accurate information and guidance to help the industry advance in an ethical manner. This current situation in the country contrasts sharply with countries like South Korea and Singapore, where regulatory bodies work closely with the private sector to ensure compliance with ethical standards, thus enhancing the credibility of their stem cell industries (Bin Abdul Aziz et al. 2022; Lovell-Badge et al. 2021). In South Korea, for instance, the use of cGMP facilities is mandated for stem cell therapy providers, ensuring high standards in product development (Bin Abdul Aziz et al. 2022; Gopalan et al. 2020). Similarly, Singapore’s alignment with international standards, particularly the ISSCR guidelines, has been instrumental in promoting responsible commercialisation of stem cell therapies (Lovell-Badge et al. 2021; Pellegrini et al. 2016). Hence, it is crucial to recognise the importance of strict implementation of national or international guidelines in a facilitative manner. Even though guidelines are not binding, they play an important role in guiding regulated actors to comply with ethically acceptable conduct. Ideally, these guidelines should help promote compliance, progress, and innovation in research under permissible boundaries (Sleeboom-Faulkner et al. 2016).

Apart from adopting well-established rules from other developed countries, Malaysian regulators could also refer to the international standard, in particular the latest guidelines established by the International Society for Stem Cell Research (ISSCR) in 2021 (hereinafter, the ISSCR 2021 guidelines). The ISSCR is the largest stem cell society in the world similar to other associations such as EuroStemCell and Stem Cell Network (SCN) (Barfoot et al. 2017; Longstaff et al. 2009). It is a globally known stem cell organisation that has been proactive in addressing ethical and regulatory issues surrounding stem cell research and therapy. It has been actively providing substantial standards and resources on any stem cell–related matters to support the integrity of this field (Sugarman et al. 2018). The ISSCR 2021 guidelines highlight five fundamental ethical principles for the ethical development of stem cell research and therapies: integrity of the research enterprise, primacy of patient welfare, respect for research participants, transparency, and social justice (Lovell-Badge et al. 2021). The role of the existing local organisations and regulators can be further strengthened perhaps through a close partnership with the ISSCR. Also, the issue of under regulation in the private sector can be addressed by establishing an independent expert review and oversight mechanism to actively implement and enforce guiding rules on research applications of stem cells, as provided by the ISSCR 2021 guidelines (Lovell-Badge et al. 2021). As argued elsewhere, enforcing stringent and active regulation of guidelines is paramount to decreasing unethical practises in the private sector (Bianco et al. 2013; Then 2009). It remains uncertain whether there is adequate communication between private sectors and regulatory authorities to actively implement these well-established rules introduced in other experienced countries and international body, in Malaysia. This research suggests that not much progress has been made in this regard. Therefore, it would be unfair to generalise all private actors as ‘unscrupulous’ when the regulatory system does not enable them to conduct their research and commercialisation activities in an ethical manner.

Risks of Unethical Conduct

Malaysia is an internationally recognised destination for medical tourism attracting 1.3 million medical tourists in 2019 (Habibu 2020). The private sector has significantly contributed to the growth of both the economy and the medical tourism sector (Ormond et al. 2014; WHO 2018). Tourists are drawn to Malaysia for therapies that are relatively more affordable compared to those available elsewhere, making the country a prominent hotspot for medical tourism, with stem cell therapies becoming an integral part of the country’s economy. The findings of this study reveal that while some private actors align their practices with ethical standards by referring to established guidelines from other countries—despite the vagueness of local guidelines and the inadequate enforcement within the country—there are still instances of other private sector practices that are overtly unethical. This study contends that the unethical activities highlighted in this paper should be addressed by the authorities to ensure that Malaysia is recognised not only as a hub for medical tourism but also as a safe and reputable destination.

Inappropriate Practice of ‘Informed Consent’

Violation of consent would not only create public distrust in stem cell therapies but also tarnish the reputation of Malaysia’s medical tourism industry. Unfortunately, some of the accounts above suggest that some of the private stem cell businesses do not uphold this fundamental ethical and legal principle. Respondent 2 revealed that there are private stem cell players who did not inform stem cell donors about the potential commercialisation of their donated specimens. Although one would argue that such an action does not bring direct harm to patients, withholding such information infringes patients’ autonomy. Also, there is a concern about the practice of obtaining consent, which does not involve a proper consultation process that should be carried out by an expert who is professionally trained in this field and has the technical knowledge. This concern was raised by respondent 6, a physician, who disagrees with the current practice, whereby in some cases, information on stem cell therapy is provided by a general practitioner rather than a specialist in the area. It has been demonstrated in another study by Fu et al. (2019) that many clinicians who provided advice on stem cell interventions in the US are not trained to deal with medical conditions for which their patients seeking treatment. Therefore, it is rather questionable if these clinicians can perform their duty and obligation in providing their patients with the right information to facilitate their patients in making an informed decision. The ISSCR 2021 guidelines emphasises the importance of empowering research participants or patients to exercise their autonomy by providing valid informed consent. Researchers or physicians should provide comprehensive and accurate details about the risks entailed regarding the offered stem cell interventions. It can be argued that based on this finding, there is a need to carry out further research to understand the local physicians’ behaviour in giving advice to patients who are seeking unproven therapies in Malaysia, because as noted in a study by Levine and Wolf (2012), even though there is a legal duty and professional obligations expected of physicians to provide a proper advice, there is a gap between their behaviour and their duty and obligations. Such research would be valuable for relevant authorities in determining appropriate intervention in the Malaysian context.

Another issue that is worth highlighting is the process of obtaining informed consent from elderly patients. It would not necessarily be of a great concern if their next-of-kin is involved during the consent-taking process. However, the possibilities of financial manipulation are material if they solely rely on their physicians, especially if it involves profit-driven physicians who will be rewarded handsomely if they provide stem cell therapy, as shared by one of the respondents. Therefore, consent made on behalf of patients should be monitored stringently with adequate witnesses to avoid exploitation and abuse. A valid consent acquisition process is fundamental to establishing trust and validity of private stem cell fields. This calls for an urgent regulatory measure regarding consent practises in the private sector and for the regulatory authorities to adopt the guidelines for consent acquisition practices established by the ISSCR (ISSCR 2019; Lovell-Badge et al. 2021). As highlighted in the updated ISSCR guidelines, respect for patients and research subjects is one of the key ethical principles.

Misleading Marketing Strategy

In a Canadian study, it was found that there were numerous private entities engaged in direct-to-consumer marketing of stem cell therapies through the advertisement of unproven therapies (Turner 2018). It was also reported that most companies do not provide substantial information on procedure-related risks; instead, they made claims about the potential benefits. Rather than based on the best available scientific evidence, these putative commercial tactics have been used to influence patients in making health-related decisions (Hawke et al. 2019; Ogbogu et al. 2018). There are also some stem cell clinics that make a bold claim that their therapies are highly efficacious and have no side effects (McLean et al. 2015). Celebrity endorsements and patient testimonies can also be found all over the media promoting these unproven therapies or products (Goddard and Waterhouse 2020; Hawke et al. 2019; McLean et al. 2015). Unfortunately, there are social media users who respond positively to this marketing strategy despite the lack of scientific evidence (Du et al. 2016). Similarly, in this study, respondent 1 reported that Malaysian stem cell industries employ the same strategy of using celebrity endorsements to promote their therapies and products. This approach could effectively attract public interest. Research has shown that celebrity endorsement has gained popularity worldwide, including in Malaysia, particularly among the younger generation, who are often enamoured with celebrities. Their online social influence and ‘endorsement’ can positively and statistically significantly impact consumer behaviour (Fauzee and Dada 2021). While it is understandable from a business perspective for private actors to employ effective strategies to promote their services and products, such practices raise ethical concerns if it is used to promote unproven therapies as it can cause harm to the public. Based on this finding, this study argues that it is crucial for relevant authorities to investigate the marketing practices surrounding unproven stem cell therapies in Malaysia. A more detailed assessment on the current marketing strategies would also be beneficial.

There are several adverse events resulting from unproven therapy that have been widely reported (Bauer et al. 2018; Cyranoski 2010; Lysaght et al. 2017; Shaikh 2010; Tuffs 2010). This shows that the risks associated with unproven therapies are material. The ISSCR 2021 guidelines also highlight the importance of establishing an oversight mechanism to address the issue of unproven stem cell–based interventions. Given this measure is lacking in the existing regulation, this suggests that there is a need to establish specific and comprehensive regulation and legally binding rules to address the increasing number of unproven therapies. Turner (2018) has argued that the absence of explicit regulatory standards and legally binding guidance documents has contributed to the increasing number of businesses entering the direct-to-consumer marketplace for unproven stem cell interventions. A similar argument has also been made in a previous study that discusses how Malaysia should move forward in regulating stem cell technology, whereby Malaysia needs to establish legislation as one of the regulatory measures (Bin Abdul Aziz et al. 2022). The accounts shared by the private actors in this study further support the importance of enacting legislation to regulate activities surrounding stem cell therapies in Malaysia including its marketing strategies.

Also, education plays an equally vital role to raise awareness to the public regarding the risk of unproven stem cell therapies. Hence, areas of ambiguity should be identified and addressed appropriately with urgent and proactive regulatory response to avoid the proliferation of such exploitative and harmful markets for unproven stem cell therapies (Ogbogu et al. 2018; Zarzeczny and Clark 2014). This was also highlighted in the study by Bin Abdul Aziz et al., whereby communication-based regulation was proposed as part of a creative regulation, which requires regulators and enables key stakeholders such as scientists to communicate with the public at large to educate and create awareness to avoid them from being exploited by fraudulent stem cell providers. Similarly, a study by Julian et al. (2020) proposed the implementation of evidence-based educational tool for both physicians and their patients, which would be useful in guiding both physicians and patients as it will distinguish established therapies and clinical research trials, provide characteristics of clinics and websites that offer unproven therapies, and include reported complications.

A Profit-Driven Culture

One of the significant contributions of this study is the revelation made by the private actors of stem cell businesses offering lucrative commissions to physicians for performing stem cell therapies. While the findings do not explicitly indicate that the practice of offering commissions to physicians as unethical from the perspectives of private actors, some of them voiced concerns about the enticing nature of these commissions, especially when the amounts are perceived as excessive for a straightforward procedure. This clearly highlights an ethically problematic environment in which dishonest physicians may exploit their patient’s trust for financial gain by persuading them to accept both costly and unproven stem cell therapies. Such practices fundamentally undermine patients’ safety and compromise their best interests. Physicians bear a vital fiduciary responsibility to address their patients’ medical needs, and a trustworthy physician–patient relationship is paramount to effective clinical practice. However, a profit-driven culture or perception can compromise these relationships, fostering mistrust between patients and physicians (Chan 2017). To ensure integrity in clinical practice, physicians should always be critical and sceptical when approached by private stem cell businesses offering novel therapies. Significantly, a strong understanding of the therapy’s background, benefits, and drawbacks must be attained. As highlighted in the ISSCR 2021 guidelines, with regard to the primacy of patient welfare, it is the obligation of researchers and physicians to ensure the welfare and wellbeing of the research subjects and patients. In this context, no stem cell–based intervention should be offered without any prospective benefit that might involve more than minimal risks.

Many stem cell–based therapies offered by private clinics and stem cell businesses are unreasonably expensive. Several instances of price gouging were noted in Malaysia’s private stem cell business with therapies costing up to RM 90,000 per therapy. Similarly, stem cell–derived cosmetics are sold at significantly higher prices than their conventional counterparts. While some of the private actors consider these prices reasonable due to the costly research required to develop the therapies, others argue that the costs are unjustified, as most of these therapies and products remain unproven. Charging exorbitant prices would also limit access to care for economically disadvantaged households seeking treatment. Despite being part of a profit-driven industry, several respondents expressed concern about the implications of such pricing on healthcare accessibility inequalities. Healthcare services should unequivocally remain available to individuals facing economic challenges. The pursuit of profit creates a conflict of interest between financial gain and patient accessibility for these institutions. Fearing that such conflicts may widen social disparities contributing to elitism in Malaysia, this study argues that the prices of these therapies should be regulated. This issue is also emphasised in the ISSCR 2021 guidelines, which uphold the principle of justice. According to the guidelines, patients should not be burdened with the financial costs of proving the safety and efficacy of experimental stem cell–based therapies, and the prices of proven interventions should be set to ensure accessibility for as many patients as possible.

This study faced with some limitations in getting a bigger sample size. This is because the stem cell community is small in the country especially in the private sector. This is due to the fact that there were a series of restricted movement orders forcing people to stay at home, and virtual meeting was not an acceptable norm in the beginning of the pandemic (Tang 2020). In addition, the interviews were conducted during a nationwide lockdown, which was unprecedented not only in the country but also across the globe. There were attempts to recruit more interviewees, but to no avail. Many people were uncomfortable to have themselves recorded on an online platform, compared to its widely acceptance as a new norm today. Be that as it may, data saturation was already achieved even with 14 interviews, whereby there were no new themes or categories emerged from the interviews (Gill et al. 2008).

Conclusion

The aim of this study is not to propose solutions or recommendations to improve the regulatory framework governing the stem cell industry in the Malaysian private sector. Instead, it offers an overview of the current status of Malaysia’s private stem cell industry and captures the perspectives of the study’s respondents, who are key stakeholders within the industry—a topic that has not been previously documented.

This study highlights several critical issues based on the insights provided by these private actors. First, respondents, particularly those affiliated with private universities, reported challenges related to limited research funding, and they viewed the current regulatory system, especially the ethical approval process, as excessively bureaucratic. Second, the findings revealed that private actors perceive the national guidelines as lacking clarity and enforcement, a concern echoing similar issues identified in the public sector in other studies. While some private actors aspire to align their practices with established guidelines from other countries, the lack of rigorous enforcement poses risks, potentially facilitating misconduct among the unscrupulous ones. Such a scenario could severely undermine the reputation of the industry and threaten Malaysia’s standing as a leading hub for medical tourism in the region. Third, this study raises concerns regarding marketing strategies that are opaque and potentially misleading, as well as questionable practices surrounding informed consent. Notably, when private actors express their concerns about the informed consent practices of their peers, it calls into question the protection of patients’ and research participants’ rights in the lucrative private stem cell sector.

These findings underscore the urgent need to reevaluate the current regulatory system to foster ethical advancements in both the private sector and public sectors. Given that some unethical practices have been acknowledged by the private actors themselves, it is crucial for authorities to address these matters with the seriousness they deserve. It can also be seen that the present ecosystem of the Malaysian private stem cell industry does not align with international standards, particularly regarding adherence to the ethical principles outlined in the ISSCR guidelines. Thus, the development and application of this promising twenty-first-century technology within Malaysia’s private sector necessitate immediate intervention from regulatory authorities. This intervention is essential to ensure that this promising technology is developed in a safe, responsible, and ethical manner that ultimately benefits the country and its citizens. However, it is important to acknowledge that the findings of this study may not be representative of the entire industry. Consequently, inclusive engagement among policy makers, regulators, and other key actors is essential to address the highlighted issues and explore additional relevant concerns, such as the approval of stem cell products. This collaborative approach will help in identifying a suitable path forward for Malaysia. The regulatory pathway for the approval of stem cell products in Malaysia is another important aspect that warrants exploration, which is beyond the scope of this paper.

Funding

This study was supported by the Fogarty International Center of the US National Institutes of Health (Grant R25TW010891).

Declarations

Ethics Approval

Approval for this study was granted by the Universiti Malaya Research Ethics Committee (UM.TNC2.UMREC-785).

Consent to Participate

Written informed consent was obtained from all participants in this study in line with the requirement of the ethical approval.

Consent for Publication

Not applicable. No identifiable data and images are included in this manuscript.

Conflict of Interest

The authors declare no competing interests.