The Efficacy of Bone Marrow Stem Cell Therapy in Hip Osteoarthritis: A Scoping Review

Abstract

Background:

Hip osteoarthritis (HOA) is a prevalent degenerative joint disease with various treatment approaches. Biological agents, such as bone-marrow derived stem cells (BM-MSC) therapy, have recently been proposed as a treatment option in the management of HOA.

Purpose:

We sought to further analyze the use of BM-MSC therapy by investigating the following questions. What is the standard preparation and practice? Does a dose response exist between stem cell therapy and clinical outcome? Does BM-MSC therapy alone produce effective clinical outcomes?

Methods:

We conducted a scoping review using the Methodological Expectations of Cochrane Intervention Reviews Manual and the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines for scoping reviews. A comprehensive search of PubMed, Embase, Cochrane CENTRAL, Scopus, SPORTDiscus, Cumulative Index to Nursing and Allied Health Literature, and Web of Science Core Collection was performed in June 2023 of studies using exclusively BM-MSC injections for the treatment of HOA. Study characteristic, injection preparation and dosage, clinical outcome measures, and adverse effect data were extracted and interpreted by 3 reviewers.

Results:

Seven studies with a total of 72 patients met the inclusion criteria. Clinical outcome following intra-articular injection of BM-MSCs was measured using the numerical pain scale, the Western Ontario and McMaster Universities Osteoarthritis Index, the visual analogue scale, and other scores, all of which showed reduction in pain and increase in functional ability across studies.

Conclusions:

This scoping review found that the efficacy of BM-MSC therapy alone in the treatment of HOA appeared beneficial, improving clinical outcomes in each study. All 7 studies used “low-dose” injections with variable follow-up times; thus, a clear dose–response relationship cannot be drawn. Future studies using high doses and analyzing long-term effects of BM-MSC injections in HOA are needed.

Introduction

Osteoarthritis (OA) is a common degenerative joint disease estimated to affect over 50 million Americans with an increasing prevalence [42]. Hip osteoarthritis (HOA) is the second most common type of OA [20]. First-line treatment for HOA typically includes physical therapy, risk factor reduction, and pain management [34,53]. Interventions for HOA refractory to first-line therapy are variable. Many conventional treatments have been studied, the most common being corticosteroid and hyaluronate injections [13,38,50]. However, in the most recent guidelines for management of HOA published by the American Academy of Orthopedic Surgeons, the usage of conventional therapies was not recommended due to the lack of clinical predictors and short-lived efficacy [37]. More recent therapeutic interventions have instead focused on targeting regenerative biologics such as platelet rich plasma (PRP) and adipose-derived stem cells (ADSCs) or bone marrow–derived mesenchymal stem cells (BM-MSCs).

Stem cell therapies for OA in general have gained attraction due to the unique characteristics of these cells and their potential to proliferate and regenerate both in vitro and ex vitro [18]. In orthopedics, the most common stem cell used is mesenchymal-derived stem cells (MSCs) due to the simple accessibility, fast cell proliferation, and long-term sustainment [18,55]. In vitro studies have shown successful induction of tissue repair and regeneration in response to injured tissue; by this same mechanism, MSCs are hypothesized to aid in the treatment of OA [4,6]. Bone marrow–derived mesenchymal stem cells, a specific subtype of MSCs, demonstrated longer proliferation as well as substantial chondrogenic capacity and regenerative potential when compared to other subtypes such as adipose-derived MSCs [27,29,35,44]. Thus, they are the focus of this review.

Bone marrow–derived mesenchymal stem cells were first transplanted for articular cartilage defect treatment in 2002 [46]. Many studies have followed suit testing BM-MSCs as a therapeutic approach to knee osteoarthritis (KOA) [30,45,49]. Systematic reviews have also been published analyzing the safety and efficacy of this treatment, define effective dosage, compare outcomes against alternative injection therapies such as hyaluronic acid (HA) or Platelet Rich Plasma (PRP), as well as determine a standard protocol for these intra-articular injections [12,22,40]. However, literature focusing on the use of BM-MSCs for HOA appears minimal at present.

To the authors’ knowledge, no review on BM-MSCs has been conducted to analyze the therapeutic efficacy in isolation. Studies have been published using BM-MSCs in conjugation with other products such as PRP, HA, or other scaffolds [8,9]. Such adjuvant therapies in the context of HOA were reported in a previous systematic review; however, the article emphasized the adjuvants as a large bias potentially altering study results. For this reason, in this review, we analyze the efficacy and safety of BM-MSCs in isolation. Such studies analyzing BM-MSCs in isolation for HOA treatment are few. Thus, a scoping review is better equipped with broad intentions to accurately report and analyze the following questions: What is the standard preparation and practice for BM-MSC therapy? Does a dose response exist between stem cell therapy and clinical outcome? Does BM-MSC therapy alone produce effective clinical outcomes?

Methods

This scoping review was conducted with guidance from the Methodological Expectations of Cochrane Intervention Reviews Manual (MECIR) and reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines for scoping review [28,43]. The search included all original articles reporting use of only BM-MSC injections for patients with HOA. Studies using adjuvant treatment with interventions other than BM-MSCs were not included. The study protocol was published in Open Science Framework as DOI: 10.17605/OSF.IO/3TX9M.

Search Strategy

A single search strategy was developed with the guidance of 2 academic health science librarians (listed in acknowledgements). The search string was written in PubMed and translated using each database’s search fields and syntax (complete search listed in the Appendix). MeSH terms, Emtree terms, and text words were used for MSCs and HOA and their synonyms. We searched Embase (Elsevier, Embase.com), Cochrane CENTRAL (Cochrane Library, Wiley), Scopus (Elsevier) SPORTDiscus, CINAHL, and Web of Science Core Collection for articles between June 13 and June 15, 2023. No date or language limitations were placed on searches.

The results of each database were exported to Endnote and uploaded to Covidence software for removal of duplicate articles. For this current review, the following inclusion criteria was applied: studies that investigated use of BM-MSCs only on humans for treatment of HOA and studies that reported outcome measures of patients treated with BM-MSCs. Consequently, the following exclusion criteria were applied: studies conducted on non-human participants, studies including participants with previous hip pathology or surgery, review studies, studies with incomplete or inaccessible data sets (such as ongoing clinical trials), and studies investigating BM-MSC with adipose-derived stem cells (ADSCs), PRP, arthroscopy, or any additional treatment methods.

Two researchers (OFP and CW) individually conducted title and abstract screening of all results and selected studies that fit the inclusion/exclusion criteria listed above. From there, the same process was used to conduct full-text reviews for each study. A third researcher (MCP) reviewed disagreements by assessing the full text and made the final decision.

Quality Assessment

Studies that fit the inclusion and exclusion criteria were critically appraised to assess methodological quality. Two researchers (OFP, CW) individually reviewed and appraised articles using the Johanna Briggs Institute (JBI) critical appraisal tools. The JBI Checklist for Case Series and Checklist for Cohort studies were used for each respective study determining if the possibility of bias in design, conduct, and analysis was addressed [32,36]. A third researcher (MCP) reviewed disagreements and made the final decision.

Data Extraction

Data were extracted using the Covidence software pre-piloted data extraction forms. The extraction table included general information (DOI, author, title, year published, journal), characteristics of study (study design, type of treatment), description of treatment (stem cell type, harvest site, preparation method, dosage of injection, number of injections, time between injections), patients demographics (number of patients, mean age, age range, sex), clinical outcome measures, outcome scores reported, length of follow-up, significant results identified, radiological results, and adverse effects. Corresponding authors were contacted to obtain pertinent data not included in the articles.

Results

The search strategy yielded a total of 3585. All articles were uploaded to Covidence where duplicates (926) were removed. After title and abstract screening 2646 articles were excluded as they either did not include the hip joint [14,51,52], used a different type of stem cell [3,54], used BM-MSC in conjugation with another treatment [41], applied the treatment for a non-HOA diagnosis [11,15,17,24], or targeted non-human studies [2,31]. Thirteen potentially relevant articles underwent a full-text review where strict inclusion and exclusion criteria were applied. A final result of 7 studies were included that described the efficacy of BM-MSC treatment on patients with HOA (Fig. 1).

Fig. 1.

PRISMA flowchart of screening and selection process of studies.

Of the included studies, 5 are cohort studies with strict inclusion/exclusion cohort criteria which examined association between exposure and outcome and 2 are case series that reported data on the individual level and did not involve hypothesis testing for cause and effect. Three articles reported on more than 1 cohort of joints, the most common additional joint being the knee [5,19,39], and the other 4 articles reported exclusively on hips [16,26,33,48]. The majority of the studies were performed and published in the United States (n = 4, 57%). Studies outside of the United States were performed and published in Iran, Chile, and Canada [5,19,33]. Additional study characteristics and treatment details are listed in Table 1.

Table 1.

Study characteristics and reported outcomes.

Study ID	Design	Sample size	Age	Treatment	Harvest site	Outcome measures	Follow-up	Overall result	Adverse events
Hauser and Orlofsky [26]	Case series	3	56-76	WBM ± dextrose	Tibia and iliac crest	Numerical Pain Score (NPS)	Minimum 6 weeks post final injection	Lower reported NPS after injection	None
Emadedin et al [19]	Cohort study	4	18-65	Autologous ex vivo expanded BM-MSC	Iliac crest	HHS; WOMAC	30 months	Significant decrease in HHS at 6 months	Local adverse effects: mild erythema and skin rash
Mardones et al [33]	Cohort study	10	24-60	Autologous ex vivo expanded BM-MSC	Posterior iliac crest	VAS; HHS; WOMAC; Other	27.5 months	Significant decrease in VAS, significant increase in mHHS at average final follow-up. WOMAC MCID reached by 64%	None
Darrow et al [16]	Case series	4	56-76	Autologous BM-MSC injection	Posterior superior iliac spine	Lower Extremity Functional Scale; NPS	22.75 days	72.3% improvement post final injection, decrease in all pain scores post-injection	None
Rodriguez-Fontan et al [39]	Cohort study	15	-	Autologous BM-MSC injection	Anterior iliac crest	WOMAC	24 months	11 hips; 63.2% were satisfied with the procedure	Seven patients noted hip joint discomfort during the first days after the procedure
Burnham et al [5]	Cohort study	20	Not listed	Autologous BM-MSC injection	Posterior iliac crest	PDQQ; NPS	12 months	Significant decrease in NPS at 3, 6, and 12 months compared to baseline. Significant increase in NPS at 3 months compared to 12 months	None
Whitney et al [48]	Cohort study	16	41-76	Autologous BM-MSC injection	Posterior iliac crest	mHHS; HOS-ADL; SF-12; WOMAC; NPS	6 months	Significant decrease in WOMAC, mHHS, HOS-ADL, NPS at 6 months	None

Sample size ranged from 4 to 20 participants with the average study having a median of 10 participants. Overall ages ranged from 24 to 76. Two studies did not report the participant data for specifically the hip group but rather published the average or range of cohort demographics including participants with a joint other than the hip being treated [5,39]. Of note, in the Hauser et al’s case series, only cases 3, 4, and 7 appropriately fit the inclusion and exclusion criteria. Complete data are listed in Table 1. Baseline severity of hip OA was reported and defined radiologically in each study, Kellgren-Lawrence and Tonnis being the most common grading scales used. Three studies used study specific criteria for OA determination which included various intra-articular joint space and cartilage loss measurements [16,26,33]. Because each study used a specific radiological grade as inclusion/exclusion criteria, they did not report outcome as a function of baseline hip OA.

The intervention across all studies was BM-MSCs. The most common site of retrieval for the BM-MSCs was from the iliac crest, either posterior or superior. Hauser and Orlofsky [26] reported the tibia as an additional site. Six of the 7 studies commented on methodology of acquiring and preparing the bone marrow concentrate for injection [5,16,19,33,39,48]. Four studies reported using bone marrow concentrate acquired through fine needle aspiration followed by centrifugation and then direct reinjected into the joint under fluoroscopic or ultrasound guidance [5,16,39,48]. Two studies performed ex vivo expansion on the aspirate and injected the expanded cultures along with the primary cells [19,33]. Complete data are listed in Table 1.

The frequency and dosage of injection varied across studies. Four studies reported a single injection of BM-MSCs to the hip joint [5,19,39,48]. Mardones et al [33] reported 3 total injections 7 days apart for all study participants. Darrow et al [16] reported 4 total injections with varying time between each injection, despite all patients being instructed to have injections 14 days apart. The average results showed injections 45 days apart after the first treatment, 12.75 days after the second, and 13 days after the third [16]. In the Hauser and Orlofsky [26] case series, the cases included in this review received 7, 6, and 2 injections over the course of 12 months, in 8-week to 12-week intervals, and in 2-month intervals, respectively.

Four studies individually quantified and reported the dosage of cells per injection [5,19,33,48]. Three studies reported both aspirate acquired and injection volume in cc or mL but did not report dosage in cells per injection [16,26,39]. Table 2 shows the dosage and outcome of all studies. Whitney et al [48] was the only study to report exact dosage concentration, and a breakdown of the cellular components per patient, reported in Table 2, is the average dosage calculated. All other studies reported the same dosage was used for each patient. Individual injection dosage ranged from 5 × 10⁵ to 3 × 10⁷ cells and 5 to 20 mL.

Table 2.

Study dose and responses reported.

Study ID	Dosage of injection	Number of injections total	NPS	WOMAC	Significant difference outcomes
Hauser and Orlofsky [26]	20 mL	2-7	Activity/Rest Baseline: 7.8 Post-injection: 0	-	N/A
Emadedin et al [19]	5.00E+05	1	-	Baseline: 45.2 ± 10.0 6 months: 27.9 ± 20.8 12 months: 26.3 ± 11.6 30 months: 29.1 ± 18.9	N/A
Mardones et al [33]	2.00E+07	3	-	Baseline: 34.5 ± 8.2 27.5 months: 19.2 ± 6.1	WOMAC: P = .15
Darrow et al [16]	5 mL	4	Resting Baseline: 3.3 Post-injection: 1.0 Activity Baseline: 5.8 Post-injection: 1.8	-	N/A
Rodriguez-Fontan et al [39]	12 mL	1		*Baseline: 40.8 ± 18.3 6 months: 19.2 ± 18.2 Latest follow-up: 20.6 ± 17	*WOMAC 6 months vs baseline < .001 Baseline vs mean latest f/u < .001
Burnham et al [5]	3.00E+07	1	Activity Baseline: 7.12 ± 1.95 3 Months: 3.57 ± 1.74 6 Months: 3.63 ± 2.53 12 Months: 6 ± 2.6	-	Baseline compared to all months P < .001 NPS at 3 months compared to 12 months P < .05
Whitney et. al [48]	6.19E+05	1	Activity Baseline: 8 ± 1 6 weeks: 6 ± 3 months: 2.5 ± 2.5 6 months: 4.5 ± 2	Baseline: 31 ± 19 6 weeks: 25 ± 13 3 months: 22 ± 14 6 months: 16 ± 14	NRS pain with activity P < .001 NRS at rest P < .001 WOMAC P = .006

^*Outcome and analysis based on hip and knee cohort outcomes, data not reported separately.

The most widely employed scoring systems for clinical outcomes was the Numerical Pain Score (NPS) (n = 4) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) (n = 4). Other outcomes included the visual analogue scale (VAS), Harris Hip Score (HHS) and modified HHS (mHHS), The Short Form-12 (SF-12), Pain Disability and Quality of Life Questionnaire (PDQQ), and a lower extremity functional scale. Five studies reported clinical outcome using more than 1 scoring system [5,16,19,33,48]. Two studies reported outcome only using an NPS or the WOMAC [26,39]. The average number of scoring systems used in each article was 2. Each study commented on either outcome statistical significance, trend, or minimally important clinical difference (MCID) and is reported in Table 1.

Two studies reported radiological outcomes [19,33]. Mardones et al [33] tracked radiographic grading (Tönnis Classification) pre-injection and post-injection and found all gradings remained without variation, except in 1 case showing an improved post-injection (from Tönnis grade 2 to 1). Emadedin et al [19] used magnetic resonance imaging (MRI) and X-ray imaging and reported articular cartilage repair in 60% of patients which when correlated with clinical response confirmed overall patient improvement.

All studies commented on the presence or absence of adverse events. Five reported no adverse events [5,16,26,33,48], whereas 2 mentioned minor adverse events reported by patients of hip discomfort, local erythema at injection site, or skin rash at injection site [19,39].

Discussion

Stem cell therapies as a possible treatment for the management of symptomatic HOA are gaining popularity in musculoskeletal medicine. To the authors’ knowledge, there have been no completed randomized controlled studies on BM-MSC injection therapy in HOA; thus, a systematic review and meta-analysis on this topic could not be carried out. In this scoping review, we used an inclusive search strategy across multiple databases to analyze the standard intervention preparation, dose response, and clinical outcomes.

The major limitation of this review is the limited number of studies regarding the effects of BM-MSCs on HOA as well as the existing studies’ method of design. Three articles measured BM-MSCs effect in more than 1 joint, and thus, their results were grouped with all joint cohorts. Some information was obtained through direct contact with corresponding authors (Burnham et al). In addition, length of follow-up varied across the studies, including 2 that were short-term (22.75 days and a minimum of 6 weeks) and therefore do not address longer-term outcomes. There were several studies with potential for biases. Based on the JBI critical appraisal tool for cohort studies [32], Burnham et al, Emadedin et al, Mardones et al, Rodrigues-Fontan et al, and Whitney et al did not mention or assess the existence of any confounding variables. Using the case series critical appraisal tool published by JBI [36], Darrow et al, and Hauser et al lacked clear reporting of and clinic demographics, limiting the population generalizability.

It should be noted that the strict inclusion criteria listed could be partially responsible for the small number of studies included. Studies on stem cell types other than BM-MSCs were excluded, as well as studies using BM-MSCs in conjugation with other interventions such as HA and PRP. One caveat to these exclusion criteria is the study published by Hauser et al who used whole bone marrow in combination with hyperosmotic dextrose. This study was still included because results on dextrose therapy individually for treatment of OA have been equivocal and contradictory, thus is not listed as a confounding variable when comparing the injections [47].

Across the articles included in this review, a difference in BM-MSC preparation was noted with various subsequent clinical results. Two studies cultured and expanded the aspirate before injection into the hip; the others injected the local aspirate directly after centrifugation. The main advantage of expanding the aspirate is to increase cell yield and desired functional properties [25]. The yield from each aspirate, however, is ultimately variable in both quality and quantity depending on age as well as site of origin [10]. Herein, both studies that injected expanded cultures used aspirate from the iliac crest and reported their dosage in terms of cells per injection [19,33]. These 2 studies subsequently noted significant improvements in clinical outcome scores (VAS and HHS) as well as radiographic evidence of cartilage repair. Neither study using expanded BM-MSCs, however, found a significant improvement in the WOMAC. Compared to the 4 studies that did not culture the aspirate, significantly improved clinical outcome scores (WOMAC, NPS, mHHS) were reported. Owing to the small sample size, no definitive conclusion can be drawn; however, future studies comparing clinical outcome in terms of WOMAC specifically should be performed in patients receiving expanded BM-MSCs vs autologous BM-MSCs. Currently, no literature is published comparing these effects.

As mentioned earlier, the justification for expansion vs no expansion pertains to dosage and the number of cells desired per injection. There is no current consensus on the optimal number of cells required for effective treatment of HOA and, to date, no study has analyzed or commented on the dosage of cells used. In studies that did not specifically quantify or report the exact dosage in number of cells, the quantity of bone marrow aspirated was reported. Similar to cells per injection, there is no current literature consensus on the optimal value of aspirate needed for effective treatment of OA [23]. Fennema et al [21] published a study analyzing the cell dosage of BM-MSC per mL of aspirate from the supra-acetabular sulcus. They recommend a collection volume of at least 8 mL for best results, where 8 mL correlated with roughly 2.6 × 10⁷ cells and was considered “high yield” [21]. All 3 studies, included in this review, reported an aspiration of greater than 8 mL of bone marrow [16,26,39]. However, the total aspirate was centrifuged and only the cellular layer was injected into the joint. Table 2 reports each study and their dosage.

A few reviews have analyzed dose response with BM-MSCs and KOA. In a multicenter randomized control trial studying BM-MSCs in KOA, Lamo-Espinosa et al [30] correlated higher dosages (1 × 10⁸ cells/injection) with better outcome VAS and WOMAC scores at 12 months follow-up. In the same trial, low-dose injections were defined as injections with 1 × 10⁷ cells and did show significant reduction in WOMAC and VAS scores, however, only until 6 months [30]. In our review, the average total number of cells used per injection across 4 articles that reported dosage was 2.28 × 10⁷, which would be considered “low dose” by Lamo-Espiniosa et al. The highest reported dosage in this review, at 6 × 10⁷ cells, would still be considered “low dose.” Additional studies should be performed using higher dosages of BM-MSCs in HOA. No significant adverse reactions were reported in the articles in this review, and prior studies have confirmed the safety of injections greater than 4 × 10⁸ [7]. The body of literature is lacking in studies using high doses of BM-MSCs for the treatment of HOA.

Regardless of dosage, each study included reported an improvement in clinical outcome. The NPS (also referred to as the numerical rating score) as a measure of OA is both valid and consistent [1]. Four articles in this review reported NPS as a measure of OA either at rest and/or with activity [5,16,26,48]. Although the baseline scores with activity varied (ranging from 5.8 to 8), all articles saw an overall decrease in the pain scores at 6 months. Burnham et al specifically saw a significant decrease in pain score past 6 months, but also reported a statistically significant increase in the pain score from 6 to 12 months. These results may align with the current literature suggesting a decreased effect of BM-MSCs 12 months post-injection on KOA, especially with “low-dose” injections [30]. Longer follow-up in the HOA cohort was tracked by 3 studies in this review. First, Emadedin et al found continual decreases in the WOMAC at 6 and 12 months, with an increase in WOMAC between 12 and 30 months [19]. However, no statistical analysis was run on the results. Second, Mardones et al [33] tracked patients with an average follow-up time of 27.5 months, range of 16 to 40 months, and reported statistically significant improvements in VAS, mHHS, and VAIL (P < .05), however, no significance in WOMAC scale. Finally, Rodriguez-Fontan et al was the third study to report outcomes with a long follow-up of 24 months. Their results, combing the hip and knee cohort, found significant differences in the WOMAC scale overall and no difference between the 6-month and 13-month WOMAC reporting. In addition, Rodriguez-Fontan was the only study included in this review to report MCID which was calculated based on a distribution approach to reflect clinically important changes in quality of life. The threshold established for MCID was 9.15 points, reached by 64% of patients, further supporting a meaningful important difference in patients receiving BM-MSC injections. Considering the small sample size of long-term follow-up studies in this review however, no definitive conclusion can be drawn regarding the function effects of injections long term.

In conclusion, the current literature published on BM-MSCs as an intervention for HOA is minimal. To address our initial questions: first, in reference to the standard preparation and practice, both factors varied across studies, with the minority using ex vivo expanded cells. Second, looking for a dose-response effect, most studies here used a standard “low-dose” injection precluding any definitive insight on a dose-response effect. Third, the clinical effect analyzed was consistent showing improvement in both the WOMAC and NPS on the short-term basis. From here, longer-term studies including a control arm as well as higher dosing is needed to more completely understand the potential of BM-MSCs in the treatment of HOA.

Appendix

Translated Search Strategies

PubMed

Searched June 13, 2023 with 241 results

(“Stem Cells” [Mesh] OR “Stromal Cells” [Mesh] OR “Mesenchymal Stem Cells” [Mesh] OR “Mesenchymal Stem Cell Transplantation” [Mesh] OR “cell transfer” [tiab] OR “cell therapy” [tiab] OR “stem cell” [tiab] OR “stem cells” [tiab] OR “stromal cell” [tiab] OR “stromal cells” [tiab] OR Mesenchymal[tiab] OR “bone marrow derived” [tiab] OR “bone marrow aspirate” [tiab] OR “BM-MSC” [tiab] OR “BM-MSCs” [tiab] OR BMSC[tiab] OR BMSCs[tiab]OR MSC[tiab] OR MSCs[tiab]) AND (“Osteoarthritis, Hip” [Mesh] OR (“Hip” [Mesh] OR “Hip Joint” [Mesh] OR hip[tiab] or hips[tiab]) AND (osteoarthrit*[tiab] OR “osteo-arthrit*” [tiab] OR arthrosis[tiab] OR arthroses[tiab] OR arthrit*[tiab] OR “Arthritis” [Mesh])).

Embase

Searched June 15, 2023 with 2052 results

(“hip osteoarthritis”/de OR ((“hip”/exp OR “arthritis”/de OR hip:ti, ab,kw OR hips:ti, ab,kw) AND (“arthritis”/de OR osteoarthrit*:ti, ab,kw OR “osteo arthrit*”:ti, ab,kw OR arthrosis:ti, ab,kw OR arthroses:ti, ab,kw OR arthrit*:ti, ab,kw))) AND (“stem cell”/de OR “stroma cell”/exp OR “mesenchymal stem cell”/de OR “bone marrow mesenchymal stem cell”/de OR “mesenchymal stem cell transplantation”/de OR “bone marrow mesenchymal stem cell transplantation”/de OR “cell transfer”:ti, ab,kw OR “cell therapy”:ti, ab,kw OR “stem cell”:ti, ab,kw OR “stem cells”:ti, ab,kw OR “stromal cell”:ti, ab,kw OR “stromal cells”:ti, ab,kw OR mesenchymal:ti, ab,kw OR “bone marrow derived”:ti,ab,kw OR “bone marrow aspirate”:ti,ab,kw OR “bm msc ”:ti,ab,kw OR “bm mscs”:ti,ab,kw OR bmsc:ti,ab,kw OR “bmscsor msc”:ti,ab,kw OR mscs:ti,ab,kw).

Cochrane Library

Searched June 13, 2023 with 124 results

([mh “Stem Cells”] OR [mh “Stromal Cells”] OR [mh “Mesenchymal Stem Cells”] OR [mh “Mesenchymal Stem Cell Transplantation”] OR “cell transfer”:ti, ab OR “cell therapy”:ti, ab OR “stem cell”:ti, ab OR “stem cells”:ti, ab OR “stromal cell”:ti, ab OR “stromal cells”:ti, ab OR Mesenchymal:ti, ab OR “bone marrow derived”:ti, ab OR “bone marrow aspirate”:ti, ab OR BM-MSC:ti, ab OR BM-MSCs:ti, ab OR BMSC:ti, ab OR “BMSCsOR MSC”:ti, ab OR MSCs:ti, ab) AND ([mh “Osteoarthritis, Hip”] OR ([mh Hip] OR [mh “Hip Joint”] OR hip:ti, ab OR hips:ti, ab) AND (osteoarthrit*:ti, ab OR osteo-arthrit*:ti, ab OR arthrosis:ti, ab OR arthroses:ti, ab OR arthrit*:ti, ab OR [mh Arthritis])).

CINAHL

Searched June 13, 2023 with 189 results

((MH “Stem Cells”) OR (MH “Mesenchymal Stem Cells”) OR (MH “Stromal Cells”) OR (MH “Cell Therapy”) OR (MH “Bone Marrow Transplantation”) OR (TI “cell transfer” OR AB “cell transfer”) OR (TI “cell therapy” OR AB “cell therapy”) OR (TI “stem cell” OR AB “stem cell”) OR (TI “stem cells” OR AB “stem cells”) OR (TI “stromal cell” OR AB “stromal cell”) OR (TI “stromal cells” OR AB “stromal cells”) OR (TI Mesenchymal OR AB Mesenchymal) OR (TI “bone marrow derived” OR AB “bone marrow derived”) OR (TI “bone marrow aspirate” OR AB “bone marrow aspirate”) OR (TI BM-MSC OR AB BM-MSC) OR (TI BM-MSCs OR AB BM-MSCs) OR (TI BMSC OR AB BMSC) OR (TI “BMSCsOR MSC” OR AB “BMSCsOR MSC”) OR (TI MSCs OR AB MSCs)) AND ((MH “Osteoarthritis, Hip”) OR (MH “Arthritis”) OR ((TI osteoarthrit* OR AB osteoarthrit*) OR (TI osteo-arthrit* OR AB osteo-arthrit*) OR (TI arthrosis OR AB arthrosis) OR (TI arthroses OR AB arthroses) OR (TI arthrit* OR AB arthrit*)) AND ((MH “Hip”) OR (MH “Hip Joint”) OR (TI hip OR AB hip) OR (TI hips OR AB hips))).

Scopus

Searched June 13, 2023 with 486 results

(TITLE-ABS-KEY (“cell transfer”) OR TITLE-ABS-KEY (“cell therapy”) OR TITLE-ABS-KEY (“stem cell”) OR TITLE-ABS-KEY (“stem cells”) OR TITLE-ABS-KEY (“stromal cell”) OR TITLE-ABS-KEY (“stromal cells”) OR TITLE-ABS-KEY (mesenchymal) OR TITLE-ABS-KEY (“bone marrow derived”) OR TITLE-ABS-KEY (“bone marrow aspirate”) OR TITLE-ABS-KEY (bm-msc) OR TITLE-ABS-KEY (bm-mscs) OR TITLE-ABS-KEY (bmsc) OR TITLE-ABS-KEY (“BMSCsOR MSC”) OR TITLE-ABS-KEY (mscs)) AND ((TITLE-ABS-KEY (hip) OR TITLE-ABS-KEY (hips)) AND ((TITLE-ABS-KEY (osteoarthrit*) OR TITLE-ABS-KEY (osteo-arthrit*) OR TITLE-ABS-KEY (arthrosis) OR TITLE-ABS-KEY (arthroses) OR TITLE-ABS-KEY (arthrit*)))).

Web of Science

Searched June 14, 2023 with 484 results

(“cell transfer” OR “cell therapy” OR “stem cell” OR “stem cells” OR “stromal cell” OR “stromal cells” OR Mesenchymal OR “bone marrow derived” OR “bone marrow aspirate” OR BM-MSC OR BM-MSCs OR BMSC OR “BMSCs OR MSC” OR MSCs) AND ((hip OR hips) AND (osteoarthrit* OR osteo-arthrit* OR arthrosis OR arthroses OR arthrit*)).

SPORTDiscus

Searched June 14, 2023 with 9 results

((DE “HUMAN stem cells”) OR (DE “BONE marrow cells”) OR (TI “cell transfer” OR AB “cell transfer”) OR (TI “cell therapy” OR AB “cell therapy”) OR (TI “stem cell” OR AB “stem cell”) OR (TI “stem cells” OR AB “stem cells”) OR (TI “stromal cell” OR AB “stromal cell”) OR (TI “stromal cells” OR AB “stromal cells”) OR (TI “Mesenchymal” OR AB “Mesenchymal”) OR (TI “bone marrow derived” OR AB “bone marrow derived”) OR (TI “bone marrow aspirate” OR AB “bone marrow aspirate”) OR (TI “BM-MSC” OR AB “BM-MSC”) OR (TI “BM-MSCs” OR AB “BM-MSCs”) OR (TI “BMSC” OR AB “BMSC”) OR (TI “BMSCsOR MSC” OR AB “BMSCsOR MSC”) OR (TI “MSCs” OR AB “MSCs”)) AND ((DE “OSTEOARTHRITIS”) OR (DE “ARTHRITIS”) OR (TI “osteoarthrit*” OR AB “osteoarthrit*”) OR (TI “osteo-arthrit*” OR AB “osteo-arthrit*”) OR (TI “arthrosis” OR AB “arthrosis”) OR (TI “arthroses” OR AB “arthroses”) OR (TI “arthrit*” OR AB “arthrit*”)) AND (DE “HIP joint” OR (TI “hip” OR AB “hip”) OR (TI “hips” OR AB “hips”)).