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Stem Cell and Regenerative Injections

What stem-cell and bone-marrow-derived injections claim to do for joints and tendons, what the evidence actually shows, and the safety and regulatory caveats.

49 citationsUpdated Oct 2026
Illustration: Stem Cell and Regenerative Injections

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Overview

Stem cell injections represent a growing area of research in traumatology and orthopaedics, with mesenchymal stem cells (MSCs) having been used in clinical practice in accordance with government health regulations [9, 33]. While regenerative medicine holds great promise for developing novel therapies that replace, repair, or promote tissue regeneration [8], there is currently insufficient evidence to recommend stem cell injections in clinical practice at this time [1]. Consequently, these therapies should continue to be studied in rigorous trials [1]. The field remains characterized by more questions than answers [10], as critical and clear phenotypic parameters for defining MSCs are uncertain and a coherent biological framework surrounding the therapeutic mechanism of action is not yet available [4].

The biological basis for these interventions is complex. Xenogeneic MSCs per se are not capable of regenerating in vivo, and whether they can serve as a vehicle to deliver target genes to host tissues remains to be tested [3]. Success may benefit from cellular engineering approaches to enhance purification, homing, cell survival, trophic effects, or immunomodulatory signaling [5]. However, more knowledge regarding the biological properties of MSCs and endothelial progenitor cells is required before these cells can be used as a routinely applied therapy in the clinical setting [14]. Furthermore, the optimal differentiation conditions for transplanted MSCs need further investigation to improve clinical efficacy [21].

Clinical outcomes have been mixed. In meniscus allograft tissue, injecting doses of MSCs (>0.1million) demonstrated active cell proliferation, migration, and robust cell survival [6]. A good relationship was found between clinical outcome and MR findings in patients treated with stem cell injection for scaphoid non-union, despite short follow-up [20]. Conversely, the use of stem cells did not improve results in relation to nerve regeneration at 90 days [12], and long-term assessment revealed no significant difference between stem cell-treated and control defects at 8 months [16]. Findings on adipose-derived stromal vascular fraction or bone marrow-derived mesenchymal stem cells were not significant enough to recommend their use for osteoarthritis in the studied model [13]. Combining stem cells and biomaterials may offer a viable therapeutic strategy to overcome limitations associated with isolated use [2]. The application of MSCs should be guided by the pathophysiology of the target disease and follow regulatory frameworks to ensure safe and effective use [33].

How It Works

Regenerative medicine aims to develop novel therapies that replace, repair, or promote tissue regeneration in orthopaedic surgery [8]. Stem cells have provided promise for the development of new therapies that can treat or possibly cure a variety of musculoskeletal conditions [7]. Combining stem cells and biomaterials may offer a viable therapeutic strategy that overcomes limitations associated with using these therapies in isolation [2]. However, critical and clear phenotypic parameters for defining mesenchymal stem cells (MSCs) are uncertain, and a coherent biological framework surrounding the therapeutic mechanism of action is not yet available [4]. More knowledge regarding the biological properties of MSCs and endothelial progenitor cells is required before using these cells as a routinely applied therapy in the clinical setting [14].

Mechanisms of Action: Stem cells possess the ability to repair and regenerate damaged tissue and serve as a promising therapeutic approach for fibrotic diseases by inhibiting the inflammatory response and secreting favorable cytokines [22]. Cellular engineering approaches may enhance purification, homing, cell survival, trophic effects, or immunomodulatory signaling in stem cell-based therapies [5]. Human mesenchymal stem cells (hMSCs) support a trophic effect on articular chondrocytes and may have therapeutic utility even after prolonged passaging [26]. Gene editing can be used to create smart stem cells capable of producing biologic drugs with antifibrotic capabilities in a controlled and localized manner [36].

Cellular Sources and Preparation: Xenogeneic mesenchymal stem cells (MSCs) are not capable of regenerating in vivo, but their potential use as a vehicle to deliver target genes to host tissues remains to be tested [3]. A simple comparison of cell numbers between adipose-derived stem cells (ASCs) and stromal vascular fraction (SVF) cells may not be meaningful because the therapeutic mode of action may be different [11]. In mice, the yield of synovial mesenchymal stem cells can be increased 50-fold by inducing inflammation [39]. Exosomes offer a promising cell-free alternative to mesenchymal stem cell therapies for upper-extremity tissue regeneration by overcoming limitations such as donor-site morbidity and tumorigenesis, though a better understanding of their mechanisms and standardized isolation methods is required before clinical application [38].

Preclinical Efficacy: Injections of doses greater than 0.1 million MSCs into meniscus allograft tissue demonstrated active cell proliferation, migration, and robust cell survival [6]. Micro-CT measurements showed increased bone healing in the cell-injected group compared to the noninjected group at postoperative day 7 in a model of skeletal injury [23]. Perivascular mesenchymal progenitors have resulted in efficacious bone regeneration across several preclinical models [17]. Platelet-rich plasma and mesenchymal stem cells have been administered as a combination therapy to promote bone regeneration in vivo [18]. Stromal cell-derived factor-1β (SDF-1b) provides potent synergistic effects supporting bone marrow stem cell-mediated bone formation and appears a suitable candidate for optimization of bone augmentation in translational protocols [35].

Musculoskeletal Applications: MSC transplantation effectively led to the regeneration of degenerated discs in a canine model [24]. The number of cells transplanted affects the regenerative capability of MSC transplants in experimentally induced degenerating canine discs [34]. Intravenous injection of multipotential stem cells neither improved the degeneration status nor preserved disk height, whereas both intravenous and direct injection methods increased glycosaminoglycan (GAG) protein and Acan gene expression relative to controls [27]. Structural properties for mesenchymal stem cell-seeded Achilles tendon repairs were typically twice those for the contralateral controls as early as 4 weeks after the procedure [25]. Intra-animal comparisons between repair tissue treated with 1-year-old MSCs and repair tissue treated with 4-year-old MSCs resulted in no significant differences in material properties including maximum stress, modulus, and strain energy density [29].

Osteoarthritis and Inflammation: Repeated intra-articular injections of platelet-rich plasma and adipose-derived stem cells alleviated inflammation and pain, promoted tissue repair, and modulated immune responses in rats with surgically induced osteoarthritis [30]. In a rat model of anterior cruciate ligament transection-induced posttraumatic osteoarthritis, the best therapeutic effects of stem cells were observed on days 7 and 14 after transection [15]. However, findings from a study on stem cell treatment for osteoarthritis were not significant enough to recommend the use of stem cells for the treatment of osteoarthritis represented in that model [13]. Long-term assessment in an equine model revealed that repair tissue filled grafted and control lesions at 8 months, with no significant difference between stem cell-treated and control defects [16].

Other Tissue Models: In a rat model of facial nerve transection, the use of stem cells did not improve results in relation to nerve regeneration at 90 days [12]. Topical embryonic stem cells enhance wound healing in diabetic rats [37]. Bone marrow-derived stem cells express the pericyte marker 3G5 in culture and show enhanced chondrogenesis in hypoxic conditions [28].

What the Evidence Shows

Clinical Efficacy and Safety

Umbilical cord–derived mesenchymal stem cells (UC-MSCs) represent a viable therapeutic option for knee osteoarthritis combined with synovitis, demonstrating clinical improvement at the end of follow-up, particularly in patients with moderate to severe pain [41]. The superiority of bone marrow aspirate concentrate (BMAC) over other orthobiologic treatments cannot be assessed due to conflicting results currently available [40]. In animal models, the intervention schedule significantly correlates with therapeutic efficacy for posttraumatic osteoarthritis; in a rat model of anterior cruciate ligament transection–induced posttraumatic osteoarthritis, the best effects of stem cell intervention were observed on days 7 and 14 after transection [15]. Repeated intra-articular injections of platelet-rich plasma (PRP) and adipose-derived stem cells (ADSCs) alleviated inflammation and pain, promoted tissue repair, and modulated immune responses in rats with surgically induced osteoarthritis [30]. However, findings in one osteoarthritis study were not significant enough to recommend the use of stem cells for the treatment of osteoarthritis represented in that model [13]. At 90 days, the use of stem cells did not improve results in relation to nerve regeneration in a rat model of facial nerve transection [12]. Long-term assessment in an equine model revealed that repair tissue filled grafted and control lesions at 8 months, with no significant difference between stem cell-treated and control defects [16]. In a canine disc degeneration model, mesenchymal stem cell (MSC) transplantation effectively led to the regeneration of degenerated discs [24].

Regarding delivery methods for injured intervertebral disks, intravenous injection neither improved the degeneration status nor preserved disk height [27]. Both intravenous and direct injection methods increased glycosaminoglycan (GAG) protein and Acan gene expression relative to controls, suggesting possible paracrine effects [27]. In a rabbit tendon model, intra-animal comparisons between repair tissue treated with 1-year-old MSCs and repair tissue treated with 4-year-old MSCs resulted in no significant differences in material properties including maximum stress, modulus, and strain energy density [29]. In a study of scaphoid non-union treatment with corticocancellous bone graft and stem cells from bone marrow, a good relationship was found between clinical outcome and MR findings in patients treated with stem cells injection despite short follow-up [20]. In a model of skeletal injury, micro-CT measurements showed increased bone healing in the cell-injected group compared to the noninjected group at postoperative day 7 [23]. In a study of revision hip replacements, the stem cell group generated significantly more new bone at the implant–allograft interface and within the graft than the control group [43]. A pre-clinical study demonstrated a beneficial effect of endogenous MSC mobilization on fracture healing, which may have translation potential to prevent or treat clinical fractures at risk of delayed or non-union fractures [45]. In a study of critical bone defects, autologous adipose-derived stem cells (ASCs)–hyaluronic acid (HA) constructs were demonstrated to be a potential treatment for the regeneration of bone defects [46]. In a study of Achilles tendon repair, the structural properties for mesenchymal stem cell-seeded repairs were typically twice those for the contralateral controls as early as 4 weeks after the procedure [25]. In a study of osteonecrosis of the femoral head, the optimal differentiation conditions for transplanted MSCs need to be further investigated to improve clinical efficacy [21]. In a study of perivascular mesenchymal progenitors, the confluence of effects resulted in efficacious bone regeneration across several preclinical models [17].

Mechanisms and Biological Framework

Although xenogeneic MSCs per se are not capable of regenerating in vivo, whether xenogeneic MSCs can be used as a vehicle to deliver target genes to host tissues remains to be tested [3]. Interventions employing PRP, MSCs and exosomes are considered in the context of degenerative osteoarthritis as a reversible chronic disease [32]. Regenerative rehabilitation seeks to integrate regenerative medicine with rehabilitation medicine to produce better clinical outcomes than the traditional linear approach [42].

Feasibility and Technical Considerations

The feasibility of injecting doses of MSCs (>0.1million) in meniscus allograft tissue with active cell proliferation, migration and robust cell survival has been demonstrated [6]. This has a clinical implication on wider use of the undifferentiated MSC for cell-based transplantation therapy for articular cartilage repair, as this option is associated with more simplified laboratory processing that would not impose on additional resources and financial burden [31]. The authors request the editor to consider their response and decide whether an erratum is required to change the terminology to 'fat pad–derived cell injection' or similar [19]. The goal of providing basic definitions for clinical colleagues regarding regenerative medicine acknowledges that there are more questions than answers in this field [10].

Research Quality and Bias

A study highlights a significant risk of reporting bias in randomized controlled trials (RCTs) and clinical trials (CTs) of MSCs for the treatment of knee osteoarthritis, with abstracts showing a significantly higher proportion of significant P values compared to main texts [51]. Spin bias was present in most MSC-related trials for knee osteoarthritis, with a higher frequency among those that utilized adipose-derived MSCs [52].

Practical Considerations

Cell Source and Preparation

A simple comparison of cell numbers between adipose-derived cultured stem cells (ASCs) and noncultured stromal vascular fraction (SVF) cells may not be meaningful because the therapeutic mode of action may be different [11]. The nonadherent cell population in the bone marrow culture serves as a complementary source of mesenchymal stem cells (MSCs) [48]. Collecting these nonadherent cells is a simple and cost-effective method to increase MSC numbers and reduce the time required for culturing for clinical applications [48]. The use of undifferentiated MSC for cell-based transplantation therapy for articular cartilage repair is associated with more simplified laboratory processing that would not impose on additional resources and financial burden [31].

Biological Mechanisms and Properties

Human mesenchymal stem cells (hMSCs) support a trophic effect on articular chondrocytes (ACs) [26]. hMSCs may have therapeutic utility even after prolonged passaging [26]. Bone marrow-derived stem cells express the pericyte marker 3G5 in culture and show enhanced chondrogenesis in hypoxic conditions, which has important implications for tissue engineering applications [28].

Clinical Application and Efficacy

The intervention schedule is significantly correlated with the therapeutic efficacy of stem cells for posttraumatic osteoarthritis (PTOA) [15]. The best effects for stem cell treatment of PTOA were observed on days 7 and 14 after anterior cruciate ligament transection (ACLT) [15]. Interventions employing platelet-rich plasma (PRP), mesenchymal stem cells (MSCs) and exosomes are considered in the context of degenerative osteoarthritis as a reversible chronic disease [32]. A good relationship was found between clinical outcome and MR findings in patients treated with stem cells injection for scaphoid non-union, despite short follow-up [20]. MSCs and insulin-like growth factor-I gene-enhanced mesenchymal stem cells (AdIGF-MSCs) indicate a benefit for the treatment of tendinitis [49].

Limitations and Terminology

The findings of a study evaluating adipose-derived stromal vascular fraction or bone marrow-derived mesenchymal stem cells were not significant enough to recommend the use of stem cells for the treatment of osteoarthritis represented in that model [13]. Terminology for mesenchymal stem cell injection for osteochondral lesions of the talus may require an erratum to change to 'fat pad–derived cell injection' or similar [19].

Key Evidence

  • [L1] There is insufficient evidence to recommend stem cell injections in clinical practice at this time, but they should continue to be studied in rigorous trials. [1] (10.1097/corr.0000000000003593)
  • [L5] Combining stem cells and biomaterials may offer a viable therapeutic strategy that may overcome the limitations associated with these therapies when they are used in isolation. [2] (10.1002/jor.24212)
  • [Paper] Although xenogeneic MSCs per se are not capable of regenerating in vivo, whether xenogeneic MSCs can be used as a vehicle to deliver target genes to host tissues remains to be tested. [3] (10.1002/jor.20385)
  • [Paper] The success of stem cell‐based therapies may benefit from cellular engineering approaches to enhance factors such as purification, homing and cell survival, trophic effects, or immunomodulatory signaling. [5] (10.1002/jor.24304)
  • [Paper] The study demonstrated the feasibility of injecting doses of MSCs (>0.1million) in meniscus allograft tissue with active cell proliferation, migration and robust cell survival. [6] (10.1002/jor.25074)
  • [Paper] Stem cells have provided tremendous promise for the development of new therapies that can treat, and possibly cure, a variety of musculoskeletal conditions. [7] (10.1002/jor.24338)
  • [L5] Regenerative medicine holds great promise for orthopaedic surgery by developing novel therapies that replace, repair, or promote tissue regeneration. [8] (10.1002/jor.20432)
  • [L2] MSC injections represent a growing area of research in traumatology and orthopaedics. [9] (10.1186/s12891-025-09123-8)
  • [L5] The goal was to provide basic definitions for clinical colleagues regarding regenerative medicine, acknowledging that there are more questions than answers in this field. [10] (10.1177/03635465211042635)
  • [L5] They argue that a simple comparison of cell numbers between ASCs and SVF cells may not be meaningful because the therapeutic mode of action may be different. [11] (10.1177/0363546519895242)
  • [Paper] At 90 days, it was observed that the use of stem cells did not improve the results in relation to nerve regeneration. [12] (10.1016/j.hansur.2018.10.214)
  • [Paper] Overall, the findings of this study were not significant enough to recommend the use of stem cells for the treatment of osteoarthritis represented in this model. [13] (10.1002/jor.20933)
  • [L5] Even though MSCs and EPCs constitute a powerful candidate cell type for regenerative medicine, more knowledge in terms of their biological properties is required before using these cells as a routinely applied therapy in the clinical setting. [14] (10.1016/s0020-1383(08)70012-3)
  • [L5] The intervention schedule is significantly correlated with the therapeutic efficacy of stem cells for PTOA, with the best effects observed on days 7 and 14 after ACLT. [15] (10.1177/03635465251326499)
  • [Paper] Long-term assessment revealed repair tissue filled grafted and control lesions at 8 months, with no significant difference between stem cell-treated and control defects. [16] (10.1002/jor.20382)
  • [Paper] The confluence of these effects have resulted in efficacious bone regeneration across several preclinical models. [17] (10.1002/jor.24284)
  • [L5] The paper highlights clinical outcomes of administering platelet-rich plasma and mesenchymal stem cells as a combination therapy to promote bone regeneration in vivo. [18] (10.1002/jor.24786)
  • [L5] The authors request the editor to consider their response and decide whether an erratum is required to change the terminology to 'fat pad–derived cell injection' or similar. [19] (10.1177/0363546514536691)
  • [L4] Despite the short follow-up we have found a good relationship with clinical outcome and MR findings in the patients treated with stem cells injection. [20] (10.1016/j.main.2011.10.091)
  • [Paper] The optimal differentiation conditions for transplanted MSCs needs to be further investigated to improve its clinical efficacy. [21] (10.1002/jor.20759)
  • [L5] Stem cells possess the ability to repair and regenerate damaged tissue and serve as a promising therapeutic approach for fibrotic diseases by inhibiting the inflammatory response and secreting favorable cytokines. [22] (10.1002/jor.24266)
  • [Paper] Micro-CT measurements showed increased bone healing in the cell-injected group compared to the noninjected group at postoperative day 7. [23] (10.1002/jor.20736)
  • [Paper] MSC transplantation effectively led to the regeneration of degenerated discs. [24] (10.1002/jor.20584)
  • [L5] The structural properties for the mesenchymal stem cell-seeded repairs were typically twice those for the contralateral controls as early as 4 weeks after the procedure. [25] (10.1002/jor.1100160403)
  • [L5] This supports a trophic effect of hMSCs on ACs. hMSCs may have therapeutic utility even after prolonged passaging. [26] (10.1002/jor.22466)
  • [L3] Contrasting to direct injection, intravenous injection neither improved the degeneration status, nor preserve disk height, however, both delivery methods increased glycosaminoglycan (GAG) protein and Acan gene expression relative to controls, suggesting possible paracrine effects. [27] (10.1002/jor.22605)
  • [L5] This has important implications for tissue engineering applications of bone marrow-derived stem cells. [28] (10.1002/jor.21043)
  • [Paper] Intra-animal comparisons between repair tissue treated with 1-year old MSCs and repair tissue treated with 4-year old MSCs resulted in no significant differences in material properties including maximum stress, modulus, and strain energy density. [29] (10.1016/j.orthres.2004.06.017)
  • [L5] Repeated intra-articular injections of PRP and ADSCs alleviated inflammation and pain, promoted tissue repair, and modulated immune responses in rats with surgically induced OA. [30] (10.1186/s13018-024-05396-2)
  • [L3] This has a clinical implication on wider use of the undifferentiated MSC for cell-based transplantation therapy for articular cartilage repair, as this option is associated with more simplified laboratory processing that would not impose on additional resources and financial burden. [31] (10.1002/jor.21413)
  • [L5] Interventions employing PRP, MSCs and exosomes are considered in this article. [32] (10.1016/j.reth.2020.07.007)
  • [L5] Mesenchymal stem cells (MSCs) have been used in clinical practice in orthopaedics and traumatology in accordance with government health regulations, but their application should be guided by the pathophysiology of the target disease and follow regulatory frameworks to ensure safe and effective use. [33] (10.1530/eor-2026-0056)
  • [Paper] The results of this study demonstrate that the number of cells transplanted affects the regenerative capability of MSC transplants in experimentally induced degenerating canine discs. [34] (10.1002/jor.21147)
  • [Paper] SDF-1b provides potent synergistic effects supporting BMSC-mediated bone formation and appears a suitable candidate for optimization of bone augmentation in translational protocols. [35] (10.1002/jor.22749)
  • [L5] Our results show that gene editing can be used to successfully create smart stem cells capable of producing biologic drugs with antifibrotic capabilities in a controlled and localized manner. [36] (10.1002/jor.25311)
  • [Paper] The study demonstrates that topical embryonic stem cells enhance wound healing in diabetic rats. [37] (10.1002/jor.21385)
  • [L5] Exosomes offer a promising cell-free alternative to mesenchymal stem cell therapies for upper-extremity tissue regeneration by overcoming limitations such as donor-site morbidity and tumorigenesis, though a better understanding of their mechanisms and standardized isolation methods is required before clinical application. [38] (10.1016/j.jhsa.2023.11.016)
  • [Paper] In mice, it became possible to increase the yield 50-fold by inducing inflammation, which makes it possible to analyze the molecular mechanisms of cartilage regeneration of synovial mesenchymal stem cells in mouse models. [39] (10.1002/jor.22753)
  • [L2] However, the superiority of BMAC over other orthobiologic treatments cannot be assessed given the conflicting results presently available. [40] (10.1186/s13018-025-06509-1)
  • [L1] Treatment with UC-MSCs was shown to be a viable therapeutic option for KOA combined with synovitis, showing clinical improvement at the end of follow-up, especially in those with moderate to severe pain. [41] (10.1186/s12891-025-09440-y)
  • [L5] Regenerative rehabilitation seeks to integrate regenerative medicine with rehabilitation medicine to produce better clinical outcomes than the traditional linear approach. [42] (10.1002/jor.24205)
  • [Paper] The results showed that the stem cell group generated significantly more new bone at the implant–allograft interface and within the graft than the control group. [43] (10.1002/jor.20598)
  • [Paper] This pre-clinical study demonstrates a beneficial effect of endogenous MSC mobilization on fracture healing, which may have translation potential to prevent or treat clinical fractures at risk of delayed or non-union fractures. [45] (10.1002/jor.24164)
  • [Paper] These results demonstrated that autologous ASCs–HA constructs is a potential treatment for the regeneration of bone defects. [46] (10.1002/jor.21184)
  • [L4] The findings confirmed that the nonadherent cell population in the bone marrow culture is a complementary source of MSCs, and collecting these cells is a simple and cost-effective way to increase MSCs numbers and reduce the time required for culturing MSCs for clinical applications. [48] (10.1002/jor.20023)
  • [Paper] These findings indicate a benefit to the use of MSCs and AdIGF-MSCs for the treatment of tendinitis. [49] (10.1002/jor.20887)
  • [L2] The study highlights a significant risk of reporting bias in RCTs and CTs of MSCs for the treatment of knee OA, with abstracts showing a significantly higher proportion of significant P values compared to main texts. [51] (10.1177/23259671251374306)
  • [L2] Spin bias was present in most MSC-related trials for knee osteoarthritis, with a higher frequency among those that utilized adipose-derived MSCs. [52] (10.1177/03635465241274155)

See Also

  • Osteoarthritis

References

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[2] Biomaterial and stem cell‐based strategies for skeletal muscle regeneration. Journal of Orthopaedic Research. 2019. DOI: 10.1002/jor.24212

[3] Survival of bone marrow‐derived mesenchymal stem cells in a xenotransplantation model. Journal of Orthopaedic Research. 2007. DOI: 10.1002/jor.20385

[4] 10.1002-jor.24343. n.d..

[5] Designer Stem Cells: Genome Engineering and the Next Generation of Cell‐Based Therapies. Journal of Orthopaedic Research. 2019. DOI: 10.1002/jor.24304

[6] Human meniscus allograft augmentation by allogeneic mesenchymal stromal/stem cell injections. Journal of Orthopaedic Research. 2021. DOI: 10.1002/jor.25074

[7] Journal of Orthopaedic Research: Special Issue on Stem Cells. Journal of Orthopaedic Research. 2019. DOI: 10.1002/jor.24338

[8] Regenerative medicine in orthopaedic surgery. Journal of Orthopaedic Research. 2007. DOI: 10.1002/jor.20432

[9] Mesenchymal stem cells injections in traumatology and orthopaedics: common practice or still a promising area with many uncertainties?. BMC Musculoskeletal Disorders. 2025. DOI: 10.1186/s12891-025-09123-8

[10] Stem Cells 101: Response. The American Journal of Sports Medicine. 2021. DOI: 10.1177/03635465211042635

[11] Comparative Clinical Outcomes After Intra-articular Injection With Adipose-Derived Cultured Stem Cells or Noncultured Stromal Vascular Fraction for the Treatment of Knee Osteoarthritis: Response. The American Journal of Sports Medicine. 2020. DOI: 10.1177/0363546519895242

[12] The use of adipose stem cells and the tubulization technique on regeneration of the facial nerve in wistar rats after transection with loss of substance. Hand Surgery and Rehabilitation. 2018. DOI: 10.1016/j.hansur.2018.10.214

[13] Evaluation of adipose‐derived stromal vascular fraction or bone marrow‐derived mesenchymal stem cells for treatment of osteoarthritis. Journal of Orthopaedic Research. 2009. DOI: 10.1002/jor.20933

[14] Biological considerations of mesenchymal stem cells and endothelial progenitor cells. Injury. 2008. DOI: 10.1016/s0020-1383(08)70012-3

[15] Days 7 to 14 May Represent an Optimal Window for Stem Cell–Based Treatment in a Rat Model of Anterior Cruciate Ligament Transection–Induced Posttraumatic Osteoarthritis. The American Journal of Sports Medicine. 2025. DOI: 10.1177/03635465251326499

[16] Enhanced early chondrogenesis in articular defects following arthroscopic mesenchymal stem cell implantation in an equine model. Journal of Orthopaedic Research. 2007. DOI: 10.1002/jor.20382

[17] Perivascular Mesenchymal Progenitors for Bone Regeneration. Journal of Orthopaedic Research. 2019. DOI: 10.1002/jor.24284

[18] The platelet‐rich plasma and mesenchymal stem cell milieu: A review of therapeutic effects on bone healing. Journal of Orthopaedic Research. 2020. DOI: 10.1002/jor.24786

[19] Mesenchymal Stem Cell Injection for Osteochondral Lesions of the Talus: Response. The American Journal of Sports Medicine. 2014. DOI: 10.1177/0363546514536691

[20] Scaphoid non-union treatment with corticocancellous bone graft and stem cells from bone marrow. Chirurgie de la Main. 2011. DOI: 10.1016/j.main.2011.10.091

[21] Fate of mesenchymal stem cells transplanted to osteonecrosis of femoral head. Journal of Orthopaedic Research. 2009. DOI: 10.1002/jor.20759

[22] Prospective application of stem cells to prevent post‐operative skeletal fibrosis. Journal of Orthopaedic Research. 2019. DOI: 10.1002/jor.24266

[23] Stem cell‐mediated accelerated bone healing observed with in vivo molecular and small animal imaging technologies in a model of skeletal injury. Journal of Orthopaedic Research. 2009. DOI: 10.1002/jor.20736

[24] Transplantation of mesenchymal stem cells in a canine disc degeneration model. Journal of Orthopaedic Research. 2008. DOI: 10.1002/jor.20584

[25] Use of mesenchymal stem cells in a collagen matrix for achilles tendon repair. Journal of Orthopaedic Research. 1998. DOI: 10.1002/jor.1100160403

[26] Trophic stimulation of articular chondrocytes by late‐passage mesenchymal stem cells in coculture. Journal of Orthopaedic Research. 2013. DOI: 10.1002/jor.22466

[27] A comparison of intravenous and intradiscal delivery of multipotential stem cells on the healing of injured intervertebral disk. Journal of Orthopaedic Research. 2014. DOI: 10.1002/jor.22605

[28] Bone marrow‐derived mesenchymal stem cells express the pericyte marker 3G5 in culture and show enhanced chondrogenesis in hypoxic conditions. Journal of Orthopaedic Research. 2010. DOI: 10.1002/jor.21043

[29] Effects of age on the repair ability of mesenchymal stem cells in rabbit tendon. Journal of Orthopaedic Research. 2005. DOI: 10.1016/j.orthres.2004.06.017

[30] Adipose-derived mesenchymal stem cells combined with platelet-rich plasma are superior options for the treatment of osteoarthritis. Journal of Orthopaedic Surgery and Research. 2025. DOI: 10.1186/s13018-024-05396-2

[31] A preliminary study comparing the use of allogenic chondrogenic pre‐differentiated and undifferentiated mesenchymal stem cells for the repair of full thickness articular cartilage defects in rabbits. Journal of Orthopaedic Research. 2011. DOI: 10.1002/jor.21413

[32] Degenerative osteoarthritis a reversible chronic disease. Regenerative Therapy. 2020. DOI: 10.1016/j.reth.2020.07.007

[33] Clinical application of mesenchymal stem cells in orthopaedics and traumatology in daily practice. EFORT Open Reviews. 2026. DOI: 10.1530/eor-2026-0056

[34] Effect of cell number on mesenchymal stem cell transplantation in a canine disc degeneration model. Journal of Orthopaedic Research. 2010. DOI: 10.1002/jor.21147

[35] Mesenchymal stem cell expression of stromal cell‐derived factor‐1β augments bone formation in a model of local regenerative therapy. Journal of Orthopaedic Research. 2014. DOI: 10.1002/jor.22749

[36] In vitro analysis of genome‐engineered muscle‐derived stem cells for autoregulated anti‐inflammatory and antifibrotic activity. Journal of Orthopaedic Research. 2022. DOI: 10.1002/jor.25311

[37] Topical embryonic stem cells enhance wound healing in diabetic rats. Journal of Orthopaedic Research. 2011. DOI: 10.1002/jor.21385

[38] The Role of Exosomes in Upper-Extremity Tissue Regeneration. The Journal of Hand Surgery. 2024. DOI: 10.1016/j.jhsa.2023.11.016

[39] Mouse synovial mesenchymal stem cells increase in yield with knee inflammation. Journal of Orthopaedic Research. 2014. DOI: 10.1002/jor.22753

[40] Progress in the clinical use of bone marrow aspirate concentrate for knee osteoarthritis: an expert opinion. Journal of Orthopaedic Surgery and Research. 2025. DOI: 10.1186/s13018-025-06509-1

[41] Intra-articular injection of umbilical cord–derived mesenchymal stem cells is safe and effective for moderate to severe knee osteoarthritis with synovitis: a double‑blinded and randomized controlled trial. BMC Musculoskeletal Disorders. 2025. DOI: 10.1186/s12891-025-09440-y

[42] Regenerative rehabilitation: The role of mechanotransduction in orthopaedic regenerative medicine. Journal of Orthopaedic Research. 2019. DOI: 10.1002/jor.24205

[43] Use of mesenchymal stem cells to enhance bone formation around revision hip replacements. Journal of Orthopaedic Research. 2008. DOI: 10.1002/jor.20598

[45] VEGF with AMD3100 endogenously mobilizes mesenchymal stem cells and improves fracture healing. Journal of Orthopaedic Research. 2018. DOI: 10.1002/jor.24164

[46] Role of autologous rabbit adipose‐derived stem cells in the early phases of the repairing process of critical bone defects. Journal of Orthopaedic Research. 2010. DOI: 10.1002/jor.21184

[48] Nonadherent cell population of human marrow culture is a complementary source of mesenchymal stem cells (MSCs). Journal of Orthopaedic Research. 2005. DOI: 10.1002/jor.20023

[49] Mesenchymal stem cells and insulin‐like growth factor‐I gene‐enhanced mesenchymal stem cells improve structural aspects of healing in equine flexor digitorum superficialis tendons. Journal of Orthopaedic Research. 2009. DOI: 10.1002/jor.20887

[51] Analysis of P Values in the Abstract Compared With the Main Text of Randomized Controlled Trials and Clinical Trials of Mesenchymal Stromal Cells for the Treatment of Knee Osteoarthritis. Orthopaedic Journal of Sports Medicine. 2025. DOI: 10.1177/23259671251374306

[52] Evaluation of Spin in Clinical Trials of Mesenchymal Stromal Cells for the Treatment of Knee Osteoarthritis: A Systematic Review. The American Journal of Sports Medicine. 2025. DOI: 10.1177/03635465241274155

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Creative Commons Corporation ("Creative Commons") is not a law firm and does not provide legal services or legal advice. Distribution of Creative Commons public licenses does not create a lawyer-client or other relationship. Creative Commons makes its licenses and related information available on an "as-is" basis. Creative Commons gives no warranties regarding its licenses, any material licensed under their terms and conditions, or any related information. Creative Commons disclaims all liability for damages resulting from their use to the fullest extent possible.

Using Creative Commons Public Licenses

Creative Commons public licenses provide a standard set of terms and conditions that creators and other rights holders may use to share original works of authorship and other material subject to copyright and certain other rights specified in the public license below. The following considerations are for informational purposes only, are not exhaustive, and do not form part of our licenses.

Considerations for licensors: Our public licenses are intended for use by those authorized to give the public permission to use material in ways otherwise restricted by copyright and certain other rights. Our licenses are irrevocable. Licensors should read and understand the terms and conditions of the license they choose before applying it. Licensors should also secure all rights necessary before applying our licenses so that the public can reuse the material as expected. Licensors should clearly mark any material not subject to the license. This includes other CC- licensed material, or material used under an exception or limitation to copyright. More considerations for licensors: wiki.creativecommons.org/Considerations_for_licensors

Considerations for the public: By using one of our public licenses, a licensor grants the public permission to use the licensed material under specified terms and conditions. If the licensor's permission is not necessary for any reason--for example, because of any applicable exception or limitation to copyright--then that use is not regulated by the license. Our licenses grant only permissions under copyright and certain other rights that a licensor has authority to grant. Use of the licensed material may still be restricted for other reasons, including because others have copyright or other rights in the material. A licensor may make special requests, such as asking that all changes be marked or described. Although not required by our licenses, you are encouraged to respect those requests where reasonable. More considerations for the public: wiki.creativecommons.org/Considerations_for_licensees

Creative Commons Attribution-NonCommercial 4.0 International Public License

By exercising the Licensed Rights (defined below), You accept and agree to be bound by the terms and conditions of this Creative Commons Attribution-NonCommercial 4.0 International Public License ("Public License"). To the extent this Public License may be interpreted as a contract, You are granted the Licensed Rights in consideration of Your acceptance of these terms and conditions, and the Licensor grants You such rights in consideration of benefits the Licensor receives from making the Licensed Material available under these terms and conditions.

Section 1 -- Definitions.

a. Adapted Material means material subject to Copyright and Similar Rights that is derived from or based upon the Licensed Material and in which the Licensed Material is translated, altered, arranged, transformed, or otherwise modified in a manner requiring permission under the Copyright and Similar Rights held by the Licensor. For purposes of this Public License, where the Licensed Material is a musical work, performance, or sound recording, Adapted Material is always produced where the Licensed Material is synched in timed relation with a moving image.

b. Adapter's License means the license You apply to Your Copyright and Similar Rights in Your contributions to Adapted Material in accordance with the terms and conditions of this Public License.

c. Copyright and Similar Rights means copyright and/or similar rights closely related to copyright including, without limitation, performance, broadcast, sound recording, and Sui Generis Database Rights, without regard to how the rights are labeled or categorized. For purposes of this Public License, the rights specified in Section 2(b)(1)-(2) are not Copyright and Similar Rights.

d. Effective Technological Measures means those measures that, in the absence of proper authority, may not be circumvented under laws fulfilling obligations under Article 11 of the WIPO Copyright Treaty adopted on December 20, 1996, and/or similar international agreements.

e. Exceptions and Limitations means fair use, fair dealing, and/or any other exception or limitation to Copyright and Similar Rights that applies to Your use of the Licensed Material.

f. Licensed Material means the artistic or literary work, database, or other material to which the Licensor applied this Public License.

g. Licensed Rights means the rights granted to You subject to the terms and conditions of this Public License, which are limited to all Copyright and Similar Rights that apply to Your use of the Licensed Material and that the Licensor has authority to license.

h. Licensor means the individual(s) or entity(ies) granting rights under this Public License.

i. NonCommercial means not primarily intended for or directed towards commercial advantage or monetary compensation. For purposes of this Public License, the exchange of the Licensed Material for other material subject to Copyright and Similar Rights by digital file-sharing or similar means is NonCommercial provided there is no payment of monetary compensation in connection with the exchange.

j. Share means to provide material to the public by any means or process that requires permission under the Licensed Rights, such as reproduction, public display, public performance, distribution, dissemination, communication, or importation, and to make material available to the public including in ways that members of the public may access the material from a place and at a time individually chosen by them.

k. Sui Generis Database Rights means rights other than copyright resulting from Directive 96/9/EC of the European Parliament and of the Council of 11 March 1996 on the legal protection of databases, as amended and/or succeeded, as well as other essentially equivalent rights anywhere in the world.

l. You means the individual or entity exercising the Licensed Rights under this Public License. Your has a corresponding meaning.

Section 2 -- Scope.

a. License grant.

1. Subject to the terms and conditions of this Public License, the Licensor hereby grants You a worldwide, royalty-free, non-sublicensable, non-exclusive, irrevocable license to exercise the Licensed Rights in the Licensed Material to:

a. reproduce and Share the Licensed Material, in whole or in part, for NonCommercial purposes only; and

b. produce, reproduce, and Share Adapted Material for NonCommercial purposes only.

2. Exceptions and Limitations. For the avoidance of doubt, where Exceptions and Limitations apply to Your use, this Public License does not apply, and You do not need to comply with its terms and conditions.

3. Term. The term of this Public License is specified in Section 6(a).

4. Media and formats; technical modifications allowed. The Licensor authorizes You to exercise the Licensed Rights in all media and formats whether now known or hereafter created, and to make technical modifications necessary to do so. The Licensor waives and/or agrees not to assert any right or authority to forbid You from making technical modifications necessary to exercise the Licensed Rights, including technical modifications necessary to circumvent Effective Technological Measures. For purposes of this Public License, simply making modifications authorized by this Section 2(a) (4) never produces Adapted Material.

5. Downstream recipients.

a. Offer from the Licensor -- Licensed Material. Every recipient of the Licensed Material automatically receives an offer from the Licensor to exercise the Licensed Rights under the terms and conditions of this Public License.

b. No downstream restrictions. You may not offer or impose any additional or different terms or conditions on, or apply any Effective Technological Measures to, the Licensed Material if doing so restricts exercise of the Licensed Rights by any recipient of the Licensed Material.

6. No endorsement. Nothing in this Public License constitutes or may be construed as permission to assert or imply that You are, or that Your use of the Licensed Material is, connected with, or sponsored, endorsed, or granted official status by, the Licensor or others designated to receive attribution as provided in Section 3(a)(1)(A)(i).

b. Other rights.

1. Moral rights, such as the right of integrity, are not licensed under this Public License, nor are publicity, privacy, and/or other similar personality rights; however, to the extent possible, the Licensor waives and/or agrees not to assert any such rights held by the Licensor to the limited extent necessary to allow You to exercise the Licensed Rights, but not otherwise.

2. Patent and trademark rights are not licensed under this Public License.

3. To the extent possible, the Licensor waives any right to collect royalties from You for the exercise of the Licensed Rights, whether directly or through a collecting society under any voluntary or waivable statutory or compulsory licensing scheme. In all other cases the Licensor expressly reserves any right to collect such royalties, including when the Licensed Material is used other than for NonCommercial purposes.

Section 3 -- License Conditions.

Your exercise of the Licensed Rights is expressly made subject to the following conditions.

a. Attribution.

1. If You Share the Licensed Material (including in modified form), You must:

a. retain the following if it is supplied by the Licensor with the Licensed Material:

i. identification of the creator(s) of the Licensed Material and any others designated to receive attribution, in any reasonable manner requested by the Licensor (including by pseudonym if designated);

ii. a copyright notice;

iii. a notice that refers to this Public License;

iv. a notice that refers to the disclaimer of warranties;

v. a URI or hyperlink to the Licensed Material to the extent reasonably practicable;

b. indicate if You modified the Licensed Material and retain an indication of any previous modifications; and

c. indicate the Licensed Material is licensed under this Public License, and include the text of, or the URI or hyperlink to, this Public License.

2. You may satisfy the conditions in Section 3(a)(1) in any reasonable manner based on the medium, means, and context in which You Share the Licensed Material. For example, it may be reasonable to satisfy the conditions by providing a URI or hyperlink to a resource that includes the required information.

3. If requested by the Licensor, You must remove any of the information required by Section 3(a)(1)(A) to the extent reasonably practicable.

4. If You Share Adapted Material You produce, the Adapter's License You apply must not prevent recipients of the Adapted Material from complying with this Public License.

Section 4 -- Sui Generis Database Rights.

Where the Licensed Rights include Sui Generis Database Rights that apply to Your use of the Licensed Material:

a. for the avoidance of doubt, Section 2(a)(1) grants You the right to extract, reuse, reproduce, and Share all or a substantial portion of the contents of the database for NonCommercial purposes only;

b. if You include all or a substantial portion of the database contents in a database in which You have Sui Generis Database Rights, then the database in which You have Sui Generis Database Rights (but not its individual contents) is Adapted Material; and

c. You must comply with the conditions in Section 3(a) if You Share all or a substantial portion of the contents of the database.

For the avoidance of doubt, this Section 4 supplements and does not replace Your obligations under this Public License where the Licensed Rights include other Copyright and Similar Rights.

Section 5 -- Disclaimer of Warranties and Limitation of Liability.

a. UNLESS OTHERWISE SEPARATELY UNDERTAKEN BY THE LICENSOR, TO THE EXTENT POSSIBLE, THE LICENSOR OFFERS THE LICENSED MATERIAL AS-IS AND AS-AVAILABLE, AND MAKES NO REPRESENTATIONS OR WARRANTIES OF ANY KIND CONCERNING THE LICENSED MATERIAL, WHETHER EXPRESS, IMPLIED, STATUTORY, OR OTHER. THIS INCLUDES, WITHOUT LIMITATION, WARRANTIES OF TITLE, MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE, NON-INFRINGEMENT, ABSENCE OF LATENT OR OTHER DEFECTS, ACCURACY, OR THE PRESENCE OR ABSENCE OF ERRORS, WHETHER OR NOT KNOWN OR DISCOVERABLE. WHERE DISCLAIMERS OF WARRANTIES ARE NOT ALLOWED IN FULL OR IN PART, THIS DISCLAIMER MAY NOT APPLY TO YOU.

b. TO THE EXTENT POSSIBLE, IN NO EVENT WILL THE LICENSOR BE LIABLE TO YOU ON ANY LEGAL THEORY (INCLUDING, WITHOUT LIMITATION, NEGLIGENCE) OR OTHERWISE FOR ANY DIRECT, SPECIAL, INDIRECT, INCIDENTAL, CONSEQUENTIAL, PUNITIVE, EXEMPLARY, OR OTHER LOSSES, COSTS, EXPENSES, OR DAMAGES ARISING OUT OF THIS PUBLIC LICENSE OR USE OF THE LICENSED MATERIAL, EVEN IF THE LICENSOR HAS BEEN ADVISED OF THE POSSIBILITY OF SUCH LOSSES, COSTS, EXPENSES, OR DAMAGES. WHERE A LIMITATION OF LIABILITY IS NOT ALLOWED IN FULL OR IN PART, THIS LIMITATION MAY NOT APPLY TO YOU.

c. The disclaimer of warranties and limitation of liability provided above shall be interpreted in a manner that, to the extent possible, most closely approximates an absolute disclaimer and waiver of all liability.

Section 6 -- Term and Termination.

a. This Public License applies for the term of the Copyright and Similar Rights licensed here. However, if You fail to comply with this Public License, then Your rights under this Public License terminate automatically.

b. Where Your right to use the Licensed Material has terminated under Section 6(a), it reinstates:

1. automatically as of the date the violation is cured, provided it is cured within 30 days of Your discovery of the violation; or

2. upon express reinstatement by the Licensor.

For the avoidance of doubt, this Section 6(b) does not affect any right the Licensor may have to seek remedies for Your violations of this Public License.

c. For the avoidance of doubt, the Licensor may also offer the Licensed Material under separate terms or conditions or stop distributing the Licensed Material at any time; however, doing so will not terminate this Public License.

d. Sections 1, 5, 6, 7, and 8 survive termination of this Public License.

Section 7 -- Other Terms and Conditions.

a. The Licensor shall not be bound by any additional or different terms or conditions communicated by You unless expressly agreed.

b. Any arrangements, understandings, or agreements regarding the Licensed Material not stated herein are separate from and independent of the terms and conditions of this Public License.

Section 8 -- Interpretation.

a. For the avoidance of doubt, this Public License does not, and shall not be interpreted to, reduce, limit, restrict, or impose conditions on any use of the Licensed Material that could lawfully be made without permission under this Public License.

b. To the extent possible, if any provision of this Public License is deemed unenforceable, it shall be automatically reformed to the minimum extent necessary to make it enforceable. If the provision cannot be reformed, it shall be severed from this Public License without affecting the enforceability of the remaining terms and conditions.

c. No term or condition of this Public License will be waived and no failure to comply consented to unless expressly agreed to by the Licensor.

d. Nothing in this Public License constitutes or may be interpreted as a limitation upon, or waiver of, any privileges and immunities that apply to the Licensor or You, including from the legal processes of any jurisdiction or authority.

Creative Commons is not a party to its public licenses. Notwithstanding, Creative Commons may elect to apply one of its public licenses to material it publishes and in those instances will be considered the “Licensor.” The text of the Creative Commons public licenses is dedicated to the public domain under the CC0 Public Domain Dedication. Except for the limited purpose of indicating that material is shared under a Creative Commons public license or as otherwise permitted by the Creative Commons policies published at creativecommons.org/policies, Creative Commons does not authorize the use of the trademark "Creative Commons" or any other trademark or logo of Creative Commons without its prior written consent including, without limitation, in connection with any unauthorized modifications to any of its public licenses or any other arrangements, understandings, or agreements concerning use of licensed material. For the avoidance of doubt, this paragraph does not form part of the public licenses.

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