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Published in final edited form as: World Neurosurg. 2025 May 21;200:124107. doi: 10.1016/j.wneu.2025.124107

Bioactive Therapies for Degenerative Disc Disease: Current State of the Art and Clinical Applications

Chibuikem A Ikwuegbuenyi 1, Alikhan B Fidai 2, Ashley Cardenas 2, Noah Willett 1, Anthony Robayo 1, Mousa Hamad 1, Ibrahim Hussain 1, Lawrence J Bonassar 2,3, Roger Härtl 1
PMCID: PMC12366758  NIHMSID: NIHMS2101550  PMID: 40409593

Abstract

Degenerative disc disease is a significant cause of chronic low back pain, often leading to disability and high health care costs. Current treatments, including physical therapy, pain management, and surgical interventions such as spinal fusion and total disc replacement, do not reverse degeneration. Bioactive therapies offer a potential alternative by targeting the underlying degenerative process. Cell-based therapies, including the use of mesenchymal stem cells and platelet-rich plasma, aim to restore disc structure and function by promoting extracellular matrix production and reducing inflammation. Early studies show potential benefits in pain relief and disc regeneration, but long-term efficacy remains unclear. Nucleus pulposus augmentation and replacement strategies, such as the use of hydrogel implants and in situ curing polymers, are aimed at restoring disc height and biomechanical function. While these strategies are promising, issues such as implant durability and migration require further study. Total disc replacement preserves motion and avoids adjacent-segment disease, but outcomes depend on patient selection and implant design. Despite encouraging results, bioactive therapies still require research to establish long-term safety and effectiveness. Advancements in biomaterials, patient selection criteria, and clinical trials will determine their role in the future management of degenerative disc disease.

Keywords: Bioactive therapies, Degenerative disc disease, Intervertebral disc degeneration, Nucleus pulposus replacement, Regenerative medicine, Stem cell therapy

INTRODUCTION

Degenerative disc disease (DDD) is a complex condition that often leads to chronic pain through mechanisms such as inflammation, mechanical nerve compression, or discogenic nerve ingrowth, which results in nerve sensitization. This article is the second in a three-part series. In the first part of this series,1 we explored the changes in the disc microenvironment across the early, herniation, and late stages of degeneration. Building on that foundation, this paper provides a comprehensive review of bioactive therapies for treating DDD. The focus is on state-of-the-art techniques, including cell-based therapies, nucleus pulposus (NP) augmentation and replacement, and total disc replacement technologies. By examining clinical studies, we aim to critically assess these therapies’ efficacy and safety while exploring their potential future directions in practice. The third paper in the series2 focuses specifically on challenges and innovations in bioactive therapies for degenerative disc disease.

EARLY-STAGE DEGENERATION

The early stages of intervertebral disc (IVD) degeneration are marked by a reduction in proteoglycan content and subsequent loss in tissue hydration. These changes compromise the disc’s mechanical integrity, hinder nutrient transport, and trigger inflammation, which drives disease progression and clinical symptoms like pain. Cell-based therapies have shown promise at this stage of degeneration. In this section we explore various therapies and examine the evidence supporting their effectiveness in treating DDD.

Mesenchymal Stem Cells

Unlike biologic therapies, which use natural or engineered medicines extracted from living cells, cell-based therapies use the live cell as the medicinal product. Novel cell-based therapies for disc degeneration involve delivering viable cells to the NP to repair or modulate the damaged disc environment.3 Stem cells, which are abundant, easy to obtain, and have low immunogenicity, are promising for IVD treatment.4 These cells include mesenchymal stem cells (MSCs), IVD-derived stem cells, and pluripotent stem cells. MSCs can be derived from a variety of sources, including bone marrow, adipose tissue, and umbilical cord. IVD-derived stem cells include NP stem cells, annulus fibrosus (AF) stem cells, and cartilage endplate stem cells; and pluripotent stem cells include induced pluripotent stem cells and embryonic stem cells.

Stem cells function in 3 main ways within degenerative IVDs: they can differentiate into IVD-like cells, support the viability of resident cells, and regulate immune responses to slow down degeneration.4 Once differentiated, MSCs can synthesize new extracellular matrix. In addition to direct differentiation, they modulate the immune response by producing anti-inflammatory cytokines and growth factors, slowing the degenerative process.5-7

Bone Marrow MSCs.

Bone marrow MSCs are nonhematopoietic stem cells known for their self-renewal and differentiation capabilities. These cells have demonstrated therapeutic benefits in treating DDD, leading to significant decreases in pain and disability.

In a study by Yokoshiwa et al.,8 2 patients receiving autologous bone marrow MSCs showed significant improvements in disc height and signal intensity on magnetic resonance imaging over 24 months. Trials by Blanco et al.,9 and Elabd et al.,10 demonstrated pain relief, improved disability scores, and successful lumbar fusion in patients with DDD following implantation or injection of bone marrow MSCs. Long-term follow-up, in Centeno and colleagues’ study with 33 patients, has shown an 85% reduction in disc bulge size and significant functional improvements without any serious adverse effects.11 These improvements exceeded commonly accepted minimum clinically important difference (MCID) thresholds for both pain and disability. Other studies echoed these findings, showing that bone marrow MSC treatment improves pain, disability, and disc quality without serious complications,12-17 though sample sizes remain small.

Bone marrow MSCs offer a promising regenerative option for patients with IVD degeneration. While early clinical trials show consistent improvements in pain relief and disc quality, more extensive, rigorous studies are necessary to confirm the long-term efficacy, safety, and mechanism of action of this treatment.

Adipose Tissue–Derived MSCs.

MSCs are readily isolated from lip-oaspirate.18,19 Clinical trials assessing the safety and efficacy of adipose tissue–derived MSCs for IVD repair have reported promising outcomes. In one phase 1 clinical trial, 8 patients (age 32–64 years) received intradiscal injections of 6.0 × 106 adipose tissue–derived MSCs combined with matrilin-3 and hyaluronic acid.20 Over a 6-month follow-up period, 75% of the patients experienced significant pain relief and improved function, with some showing radiological improvement. In another phase 1 trial, 10 patients (age 30–64 years) received higher doses of adipose tissue–derived MSCs (2 × 107 or 4 × 107) combined with hyaluronic acid.21 This trial showed comparable results, with 60% of the patients reporting significant improvements in pain and function after 12 months.

Although these early clinical trials indicate that adipose tissue–derived MSCs are well tolerated and effective in reducing pain and enhancing disc regeneration, the small sample sizes and short follow-up periods highlight the need for more extensive, randomized, and controlled trials. Larger studies with extended observation periods will be crucial to determining the long-term safety and effectiveness of this treatment for patients with DDD.

Umbilical Cord MSCs.

Umbilical cord MSCs are primarily found in Wharton’s jelly and are known as Wharton’s jelly mesenchymal stem cells (WJMSCs). Wharton’s jelly is the gelatinous connective tissue surrounding the umbilical vessels and serves as a rich source of MSCs due to its abundant extracellular matrix and stromal cell content. They offer distinct advantages due to their robust proliferation and extensive differentiation abilities, low immunogenicity, and lack of tumorigenicity.22 Unlike many other stem cells, WJMSCs are free from ethical constraints, but they cannot be obtained autologously for patients with DDD. Compared to most other MSCs, WJMSCs represent a less differentiated and more versatile type of stem cell.

We found only one clinical study using umbilical cord MSCs, reporting their use in patients. The study involved 2 patients, one 38 years old and the other 45 years old, who received intradiscal injections of 1 × 107 cells per disc.23 They were then monitored for 24 months. The study showed that the patients experienced significant pain relief and improved function and had increased signal intensity on magnetic resonance imaging, with no adverse events. While these results are promising, the small sample size highlights the need for larger studies to confirm these findings and establish broader clinical efficacy and safety for umbilical cord MSC/WJMSC–based treatments.

In treating DDD, bone marrow MSCs, and adipose tissue–derived MSCs stand out for their potential and therapeutic effectiveness. Bone marrow MSCs are favored for their robust differentiation capabilities and established clinical outcomes, often leading to significant reductions in pain and disability through enhancing disc cell survival and extracellular matrix production. Adipose tissue–derived MSCs, easily harvested from adipose tissue, also show promise in differentiating into NP cells and enhancing extracellular matrix stability, though they have a lower osteogenic potential than bone marrow MSCs. Collectively, these cell types exemplify the cutting-edge of regenerative medicine in treating DDD, reflecting a critical area of ongoing clinical research and application.

Mesenchymal Precursor Cells

Mesenchymal precursor cells (MPCs), unlike MSCs, which can be found in various tissues, are typically isolated from bone marrow. They are considered a more primitive and potent form of stem cell, possessing higher proliferative capacities and differentiation potentials. MPCs can also differentiate into multiple cell types, including osteoblasts, chondrocytes, and adipocytes, making them highly versatile for various regenerative medicine applications.24 One phase 1/phase 2 clinical trial conducted by Mesoblast (Melbourne, Victoria, Australia) involved 100 patients (age 18–75 years) who received intradiscal injections of 6 million or 18 million MPCs mixed with hyaluronic acid. Over a 36-month follow-up period, the study observed significant pain relief, improved disability scores, and enhanced quality of life, with no significant adverse events.25 The study highlights the potential of MPCs for treating degenerative disc disease. However, more extensive studies are needed to confirm these findings and address logistical challenges in MPC expansion and immune matching.

Disc-Derived Progenitor Cell Therapy

Beyond mesenchymal stem and precursor cells, disc-derived progenitor cells have emerged as another biological strategy explicitly tailored to the IVD environment. These cells are isolated from donor disc tissue and expanded into a population with high chondrogenic potential and immunomodulatory properties.26,27 Unlike generic MSCs, discogenic cells are phenotypically optimized for matrix production within the unique hypoxic, avascular disc milieu.26 Preclinical studies have demonstrated their ability to restore disc height and extracellular matrix content, including aggrecan and collagen II, laying the groundwork for clinical translation in DDD.26

A recent Food and Drug Administration (FDA)-approved, multicenter Phase I/II randomized controlled trial by Gornet et al. evaluated the use of high-dose allogeneic disc progenitor cells in patients with symptomatic lumbar DDD.28 Patients receiving a single intradiscal injection demonstrated statistically significant improvements in pain (visual analog scale score, −62.8%, P = 0.0005), disability (Oswestry Disability Index), and quality of life (EQ-5D), with sustained effects through 104 weeks. Notably, significant increases in disc volume were observed on magnetic resonance imaging at both 52 and 104 weeks. Improvements in the high-dose group exceeded established MCID thresholds for the visual analog scale (≥20 mm), Oswestry Disability Index (≥15 points), and EQ-5D (≥0.08), underscoring clinical as well as statistical significance. This study represents an important step toward clinical translation, offering early high-level evidence supporting the safety and potential efficacy of discogenic cell therapy for DDD.

Platelet-Rich Plasma

Injecting platelet-rich plasma (PRP) into the disc has emerged as a promising treatment for DDD.29 PRP injections enhance collagen production, promote epithelial cell regeneration, and stimulate angiogenesis, improving IVD metabolism and alleviating low back pain.30,31 Furthermore, the growth factors in PRP, such as TGF-β, PDGF, EGF, and IGF-1, effectively increase cell viability and stimulate extracellular matrix metabolism and IVD cell proliferation.32-34 Our search identified several studies exploring the use of PRP for IVD regeneration. A prospective clinical trial involving 31 patients (mean age 53.4 years) showed significant pain relief and improved lumbar function in 71%—however, one case of discitis required surgery, indicating the need for further randomized controlled trials.35 A retrospective analysis of a previous randomized trial with 15 patients (mean age 33.9 years) also demonstrated significant improvements in low back pain and disability.36 Another retrospective study that included 37 patients (age 14–72 years) who were treated with high-concentration PRP demonstrated significant improvements in pain and function, with high patient satisfaction.37 A phase 1 clinical trial (15 patients, age 32–76 years) using stromal vascular fraction combined with PRP, showed significant improvements in pain and functional scores.38 However, the small sample size calls for further research. These studies collectively suggest promising results for PRP therapy in treating discogenic low back pain but emphasize the need for more extensive research to confirm long-term efficacy and safety.

HERNIATION

Herniation represents one of the most prevalent and challenging clinical manifestations of intervertebral disc degeneration. The progressive breakdown of disc integrity leads to the extrusion of disc material, frequently affecting the posterolateral region and often resulting in significant nerve root compression and associated pain. Treatment for herniated discs has ranged from conservative approaches to surgical interventions, yet the limitations of these methods in fully addressing degeneration have sparked a growing interest in regenerative therapies. This has paved the way for advanced strategies such as NP augmentation, NP replacement, and AF repair, all of which aim to relieve symptoms and restore disc function and structure. In the following section, we will explore these emerging therapies and their potential impact on managing this stage of DDD.

NP Augmentation and Replacement

In 2004, the US FDA approved total disc replacement for treating DDD, offering an alternative to fusion techniques, preserving motion and reducing adjacent-segment stress.39-41 Since then, the focus has shifted toward technologies that replace only the NP, aiming to restore disc height and maintain range of motion while reducing the invasiveness of the procedures. These technologies range from pre-formed mechanical devices to in situ curing hydrogels, each designed to mimic the biomechanical properties of the native NP.42,43

Early NP Replacement Technologies.

One of the earliest NP replacement methods involved preformed mechanical devices such as the Fernstrom ball, a stainless-steel sphere designed to restore disc height and redistribute forces.44 Clinical trials involving over 250 patients showed promising short-term results, but complications such as subsidence into vertebral endplates limited its long-term success.45 This initial concept paved the way for more refined approaches focused on improving material properties and surgical techniques.

Modern NP Replacement Devices.

Recent advancements have improved upon these early designs, using biocompatible materials that better mimic the NP’s function. For instance, the NuBac disc arthroplasty system (developed by Pioneer Surgical Technology, Inc., Marquette, Michigan, USA, which was subsequently acquired by RTI Surgical, which in turn was transformed into Evergen [Alachua, Florida, USA] in 2024) used an ovular ball-and-socket design made of polyetheretherketone-Optima (Invibio Ltd., West Conshohocken, Pennsylvania, USA).46 This device showed excellent results in clinical trials, with a 75.9% reduction in disability and an 80.3% decrease in pain over 2 years.47

Another notable device is the Newcleus (Centerpulse Orthopedics, Winterthur, Switzerland, which was subsequently acquired by Zimmer Biomet [Warsaw, Indiana, USA] in 2003), a polycarbonate urethane memory-coil prosthesis.42 Early trials with 5 patients reported reduced back pain and disability without device extrusion.48 Seventeen years later, finite element analysis improved the design, enhancing biomechanical performance by increasing axial stiffness and better simulating the native NP’s function.49 This iterative improvement process reflects the ongoing evolution of NP replacement technologies.

Hydrogel Implants for NP Replacement.

Hydrogels have emerged as a promising solution for NP replacement due to their ability to absorb water and mimic the NP’s biomechanical properties.50 The PDN prosthetic disc nucleus (Raymedica Inc., Minneapolis, Minnesota, USA; subsequently acquired by Centinel Spine, West Chester, Pennsylvania, USA), made from a polyethylene jacket filled with polyacrylamide pellets, demonstrated the ability to restore disc height and range of motion in cadaveric studies,51 with an 88% surgical success rate in clinical trials.52 However, long-term follow-up revealed challenges such as device subsidence and a reduction in range of motion over time.53,54

NeuDisc (Replication Medical, Inc., New Brunswick, New Jersey, USA), a hydrogel implant without an outer jacket, expands tenfold upon hydration and includes polyester fiber mesh to prevent bulging.55 Biomechanical studies have shown that NeuDisc effectively resists fatigue and radial bulging under axial compression, closely replicating the properties of the native NP.55 Early pilot clinical trials are still ongoing.56

Another hydrogel device, GelStix (Replication Medical, Auburn Hills, Michigan, USA), offers a minimally invasive approach for NP replacement.57 The matchstick-shaped hydrogel expands upon hydration and has significantly improved pain (65.3%) and function (38.3%) in patients with DDD.58 However, complications such as implant extrusion causing nerve root compression have been reported,59 highlighting the need for improved design to prevent such issues.

In Situ Curing Hydrogels for NP Replacememt.

In situ curing hydrogels offer another advancement in NP replacement. These materials are injected into the disc space in liquid form and solidify in situ, reducing the risk of extrusion and ensuring a more precise fit. NuCore (Spine Wave, Inc., Shelton, Connecticut, USA), a silk and elastin copolymer hydrogel,60,61 has been shown to restore disc height and stability, with clinical trials reporting an 89.2% reduction in leg pain and a 76.7% improvement in disability.62 Despite these positive outcomes, the device extrusion rate of 13.3% in long-term trials indicates the need for further refinement.63

Similarly, BioDisc (CryoLife, Inc., Kennesaw, Georgia, USA), a serum albumin and glutaraldehyde-based hydrogel, showed promising results in biomechanical and clinical studies.64 It restored disc height in animal models and achieved a 77.6% reduction in disability and a 72.4% improvement in pain in human trials.65 However, a 20% extrusion rate remains a significant concern for its widespread adoption.65

In Situ Curing Polymers for NP Replacement.

In situ curing polymer implants represent a significant advancement in NP replacement. In this technology, catheters are used to insert balloon-like structures into the evacuated AF. These balloons are then filled with curing polymers that expand and solidify, mimicking the natural nucleus.66,67 The DASCOR disc arthroplasty system (Disc Dynamics Inc., Eden Prairie, Minnesota, USA), the first of such devices, used a polyurethane balloon filled with a curing core. The DASCOR disc arthroplasty system effectively restored disc height and stability in biomechanical and clinical studies.66,68 However, long-term trials revealed device extrusion and biocompatibility issues, ultimately hindering its FDA approval despite promising European results.68,69

The Kunovus Disc Device (Sydney, Australia) and the PerQdisc (Spinal Stabilization Technologies, Ltd., Kilkenny City, Ireland) are more recently developed in-situ curing polymer implants. The Kunovus Disc Device utilizes a silicone balloon filled with dualcuring polymers and has shown positive early clinical trial outcomes.67 The PerQdisc, featuring separate external and internal chambers for independent access and enhanced load response, also demonstrates effective biomechanical performance.70 While detailed clinical data for the PerQdisc remains limited, early reports and ongoing trials (clinicaltrials.gov identifiers NCT05508360 and NCT05732818) indicate significant potential for these in situ curing polymer implants in NP replacement and spine stabilization.71

Shaping the Future of NP Replacement.

These advancements highlight the potential of NP replacement technologies in treating DDD while preserving the motion and function of the spine. Hydrogels, in particular, represent a significant leap forward due to their biomimetic properties and ability to be delivered via minimally invasive procedures. However, long-term durability, subsidence, and extrusion must be addressed to ensure broader clinical adoption. Moving forward, the focus will likely remain on refining the materials and methods used for NP replacement. Continued innovation in biomaterials and more robust clinical trials will be essential for demonstrating the long-term safety and efficacy of these devices, which hold the potential to revolutionize DDD treatment.

Annulus Fibrosus Repair

Annular repair or closure is a current strategy for managing DDD by preventing NP leakage. Techniques like AF sutures help maintain IVD height and lumbar stability but are unsuitable for prolonged high mechanical loading.72 Devices developed for annular closure include the Xclose tissue repair system (Anulex Technologies, Minnetonka, Minnesota, USA), the AnchorKnot suture passing device (Anchor Orthopedics, Toronto, Ontario, Canada), and the Barricaid annular closure device (Intrinsic Therapeutics, Woburn, Massachusetts, USA).73 AF repair can decrease nerve root irritation and postoperative pain, reduce inflammatory mediator release and chemical radiculitis, facilitate AF scar healing, and maintain NP pressurization to reduce herniation recurrence.73 However, the effectiveness of these devices in preventing recurrent lumbar disc herniation is still debated.

A randomized clinical trial with 554 microdiscectomy patients with large annular defects showed a symptomatic recurrent disc herniation rate of 25.3% without closure, compared to 12% with annular closure at a 2-year follow-up.74 This difference persisted at 3 years, with rates of 14.8% in the closure group versus 29.5% in the control group and higher reoperation rates in the control group (19.3% vs. 11%).75 No increase in adverse events was noted in the annular closure group, whereas serious adverse events were more frequent in the control group due to reherniation. Meta-analyses also show significant reductions in symptomatic recurrent disc herniation (2.9% vs. 7.9%) and improvements in disability and pain scores for patients treated with annular closure devices, with no significant difference in postoperative complications.76 Annular closure devices, particularly for larger annular defects, may reduce re-herniation rates and the need for aggressive discectomy, potentially lowering the incidence of back pain after surgery.

Despite these benefits, clinical evidence shows that AF repair techniques, including soft tissue repair kits and bone-anchored annular closure devices, are not without disadvantages. Studies indicate that bone-anchored devices are associated with complications such as longer operative times, increased blood loss, and nerve root injuries.74 Additionally, device failure, infection, and significant operative complications highlight the need for further research to determine these devices’ long-term safety and efficacy.77

END-STAGE DEGENERATION

End-stage degeneration is characterized by severe structural and biochemical deterioration of the intervertebral disc, often involving significant loss of disc height, osteophyte formation, and facet joint degeneration. At this stage, conservative treatments and partial disc replacement therapies, such as NP augmentation, are often inadequate to alleviate symptoms and restore function. As a result, the standard of care shifts toward more comprehensive solutions, such as total disc replacement (TDR) or spinal fusion, which aim to relieve pain, restore spinal alignment, and maintain or restore motion. Although TDR offers a motion-preserving alternative to fusion, patient selection, long-term outcomes, and advancements in implant design remain critical areas of focus for optimizing outcomes.

Total Disc Replacement

TDR has emerged as a viable alternative to spinal fusion for patients with DDD, particularly those seeking to preserve motion. The fundamental goal of TDR is to maintain mobility by replacing the damaged intervertebral disc with an artificial one, thus avoiding the stiffness associated with fusion procedures. Early designs, such as the Charité (DePuy Synthes, Raynham, Massachusetts, USA) and ProDisc-L (Centinel Spine, West Chester, Pennsylvania, USA), were developed to mimic the biomechanics of a healthy disc. These devices utilize ultra-high-molecular-weight polyethylene and cobalt-chromium alloy to facilitate natural motion while distributing spinal loads.78

Proper patient selection is vital to achieving successful outcomes. Ideal candidates for TDR are those with single-level DDD and no significant spinal deformities, facet joint arthritis, or osteoporosis. In the United States, TDR is primarily approved for single-level lumbar and cervical DDD, with strict criteria for patient eligibility. European guidelines are broader, allowing for multilevel disc replacements and hybrid surgeries combining TDR and spinal fusion.78

Clinical outcomes for TDR have been promising, showing significant improvements in pain relief, range of motion, and quality of life compared to results achieved with fusion. Long-term studies indicate durable outcomes, with some patients maintaining benefits for over 10 years.79 However, complications such as implant subsidence, heterotopic ossification, and adjacent-segment disease remain concerns, particularly with the use of older designs. Recent advancements in implant materials and techniques have reduced these risks, while hybrid TDR-fusion constructs offer additional options for patients with more complex pathologies.78

As the field evolves, future biomaterials and implant design innovations will further enhance TDR’s safety, durability, and functional outcomes.

LIMITATIONS

While this review highlights promising innovations in bioactive therapies for DDD, several limitations must be acknowledged. Much of the available clinical evidence is based on small, early-phase trials with limited follow-up. Direct comparisons between therapies are difficult due to heterogeneity in study designs and outcome measures. Importantly, many of these studies apply restrictive inclusion criteria—focusing on patients with isolated discogenic low back pain and excluding those with more advanced or complex spondylotic pathology—which limits the generalizability of their findings. Despite early promise, many stem cell and mechanical disc replacement therapies are actively marketed as restorative solutions without robust clinical evidence, raising concerns about commercial exploitation and the need for independent, long-term validation.

Finally, although several studies report statistically significant reductions in pain or disability, these improvements are not always assessed against MCID thresholds, making it difficult to determine their real-world clinical relevance. Moreover, long-term outcomes remain underreported for many cell- and biologic-based therapies. This may reflect the relatively recent introduction of these treatments, the logistical and financial burden of extended follow-up, challenges with long-term patient retention, and regulatory factors that can delay or limit longitudinal study design and execution.

CONCLUSIONS

Bioactive therapies for DDD represent a growing field of innovation with the potential to address the limitations of traditional treatments such as spinal fusion. Current advances in cell-based therapies, NP augmentation and replacement, and disc replacement technologies show promise in restoring disc function, reducing pain, and preserving mobility. However, despite encouraging results in early clinical trials, long-term efficacy and safety remain areas that require further investigation. As more robust clinical data become available, these therapies may become viable additions to current surgical interventions, providing patients with less invasive, motion-preserving treatment options. Future research should continue to refine these technologies while exploring patient selection criteria, cost-effectiveness, and long-term outcomes to fully realize their clinical potential.

ACKNOWLEDGMENTS

We acknowledge the contribution of Anne Stanford, ELS, who provided professional editing services, and Thom Graves who provided the spine illustration for Figure 1.

Figure 1.

Figure 1.

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Various types of therapies for different stages of degenerative disc disease (DDD). Early-stage DDD: Stem cell therapy involving mesenchymal stem cells (MSCs) from adipose tissue and bone marrow, processed and prepared for intradiscal injection. Herniation: Devices for herniation treatment, including the Prosthetic Disc Nucleus (PDN), Neudisc prehydration implant (PDN and Neudisc images both reprinted from The Spine Journal, 5(6, Suppl), Goins ML, Wimberley DW, Yuan PS, Fitzhenry LN, Vaccaro AR, Nucleus pulposus replacement: an emerging technology, S317–S324, copyright 2005, with permission from Elsevier), and Barricaid device (from Barricaid website [https://barricaid.com/fda-approved-annular-closure-device/]; published with permission from Intrinsic Therapeutics). End-stage DDD: Total disc replacement (TDR) devices used in the cervical spine (from SPINEMarketGroup. Are the cervical discs back again? Updated list of the 40 main players! (https://thespinemarketgroup.com/are-the-cervical-discs-back-againupdated-list-of-40-main-players/; published with permission from SPINEMarket Group), Prodisc-L, Charité III (Prodisc-L and Charité III images both from Kaner T, Ozer AF. Dynamic stabilization for challenging lumbar degenerative diseases of the spine: a review of the literature. Advances in Orthopedics. 2013; 2013[1]:753,470; Creative Commons license), and postoperative radiograph obtained 1 year after minimally invasive transforaminal lumbar interbody fusion. MI-TLIF, minimally invasive transforaminal lumbar interbody fusion.

Conflict of interest statement:

R. Härtl reports consulting for Depuy Synthes, Brainlab, and Aclarion and financial relationships with RealSpine and OnPoint. This work was supported by the National Institutes of Health (grant numbers 5TL1TR002386-08, NIH 3T32AR078751-03S1, and 5TL1TR0002386-07).

Abbreviations and Acronyms

AF

Annulus fibrosus

DDD

Degenerative disc disease

FDA

Food and Drug Administration

IVD

Intervertebral disc

MCID

Minimal clinically important difference

MPC

Mesenchymal precursor cell

MSC

Mesenchymal stem cell

NP

Nucleus pulposus

PRP

Platelet-rich plasma

TDR

Total disc replacement

WJMSC

Wharton’s jelly mesenchymal stem cell

Footnotes

CRediT AUTHORSHIP CONTRIBUTION STATEMENT

Chibuikem A. Ikwuegbuenyi: Conceptualization, Data curation, Investigation, Methodology, Writing – original draft, Writing – review & editing. Alikhan B. Fidai: Data curation, Investigation, Visualization, Writing – original draft, Writing – review & editing. Ashley Cardenas: Data curation, Investigation, Writing – original draft, Writing – review & editing. Noah Willett: Writing – review & editing. Anthony Robayo: Writing – review & editing. Mousa Hamad: Writing – review & editing. Ibrahim Hussain: Conceptualization, Methodology, Supervision, Writing – review & editing. Lawrence J. Bonassar: Conceptualization, Methodology, Project administration, Resources, Software, Supervision, Writing – review & editing. Roger Härtl: Conceptualization, Methodology, Project administration, Resources, Software, Supervision, Visualization, Writing – review & editing.

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