Stem Cell Therapy
Original Editor - Malisha van der Berg
Top Contributors - Malisha van der Berg, Vidya Acharya and Alexandra Stead
Introduction
Stem cell therapy is a form of regenerative medicine that uses self-renewing cells capable of differentiating into other cell types, aiming to repair tissue and modulate disease.[1] Mesenchymal stem cells (MSCs) are the most widely used type in practice, owing to their ease of collection, safety profile and immunomodulatory properties.[2][3] Patients increasingly present to physiotherapy having received, or considering, these treatments alongside conventional rehabilitation.[4]
MSCs can be sourced from bone marrow, adipose tissue, umbilical cord, placenta and dental pulp, and are being investigated across musculoskeletal, neurological, cardiovascular, respiratory, endocrine and reproductive conditions.[2][5]
Historical Development of Stem Cell Therapy
Stem cell research has developed over more than a century, with the pace of clinical translation accelerating markedly from the 1990s onward. The table below traces the key milestones.
| Period | Development |
|---|---|
| 1868 | Concept of bone marrow stem cells first described by a German pathologist studying wound healing.[2] |
| 1957–1959 | Dr E. Donnall Thomas pioneered the first allogeneic haematopoietic stem cell transplant, between identical twins.[2] |
| 1988 | First fetal mesencephalic tissue transplant for Parkinson’s disease.[2] |
| 1992–1993 | Human bone marrow MSCs first isolated, cultured and infused into patients.[5] |
| 1995 | Professor Arnold Caplan isolated and cultured MSCs from bone marrow and infused them back into patients, marking the transition of MSC research from laboratory to clinical application.[2] |
| 1998 | Human embryonic stem cell (ESC) lines were successfully established, raising ethical concerns over embryo destruction.[2] |
| 2006–2007 | Induced pluripotent stem cells (iPSCs) were generated by reprogramming adult somatic cells, offering a way to obtain pluripotent cells without the ethical concerns associated with embryonic sources.[2] |
| 2009 onward | Regulatory frameworks expanded internationally, and clinical trial numbers grew substantially, with over 8,200 interventional stem cell studies registered on ClinicalTrials.gov by November 2024, and more than 950 MSC-based clinical trials submitted to the FDA over 25 years.[2][5] |
| 2018–present | Several MSC-based products have received regulatory approval globally for specific indications, including graft-versus-host disease and complex perianal fistula in Crohn’s disease. CRISPR-based genetic engineering of MSCs has emerged as an active area of research aimed at improving safety and efficacy.[2][6]
In December 2024, the FDA approved the first MSC-based therapy for paediatric steroid-refractory acute graft-versus-host disease, remaining one of only a small number of formally approved MSC indications.[7] |
The animation video below explains stem cells in simple words and also explains 2006 iPSC discovery
Note: Most stem cell applications, including those in this document, remain investigational.
Physiological Rationale for Stem Cell Therapy
Several mechanisms are thought to underpin MSC therapy, and together explain both its broad theoretical applicability and its inconsistent clinical results.
Differentiation Potential
MSCs are multipotent, meaning that under laboratory conditions they can differentiate into:[3]
- Osteoblasts (bone-forming cells)
- Chondrocytes (cartilage-forming cells)
- Adipocytes (fat cells)
In practice, however, direct transdifferentiation into functioning tissue occurs far less than what was originally hoped. Current evidence points to a different, indirect mechanism as the primary driver of clinical effect.[1]
Paracrine Signalling
The dominant mechanism now understood to underlie MSC therapy is paracrine signalling: The release of bioactive molecules, that act on the surrounding tissue and modulate the body’s own repair processes.[1][9]
This paracrine secretome includes:[9]
- Neurotrophic factors (brain-derived neurotrophic factor and nerve growth factor)
- Angiogenic factors (vascular endothelial growth factor)
- Anti-inflammatory cytokines
These bioactive molecules together support tissue repair, reduce inflammation, and encourage the recruitment of the body’s own regenerative processes, rather than becoming new tissue themselves.[1][9][10]
Immunomodulation
MSCs promote regulatory T cells and shift macrophages towards an anti-inflammatory phenotype.[3][9]
Umbilical cord-derived MSCs (UC-MSCs) illustrate this particularly well:[11]
- They suppress T cell over activation and promote regulatory T cell differentiation via Interleukin (IL)-10 secretion.
- Block Th17 differentiation via TGF-β and chitinase-3-like protein 1 acting through STAT3.
- Drive macrophage polarisation from a pro-inflammatory M1 towards a reparative M2 phenotype through combined metabolic and epigenetic mechanisms
Inflammasome Inhibition
A further, more recently characterised mechanism is UC-MSC suppression of the NLRP3 inflammasome, which drives much of the tissue-damaging cascade in acute and chronic inflammation. This occurs through several non-classical pathways:[11]
- Including activation of a cPWWP2A-Rb1-AMPKα2 signalling axis that prevents NLRP3 assembly,
- Inhibition of macrophage glycolysis
- Mitochondrial quality control that clears damage-associated molecular patterns before they can trigger further inflammasome activation.
Homing and Migration
Following administration, MSCs have the capacity to migrate toward areas of tissue damage or inflammation. They are guided by chemical signals released from the injured tissue itself. Signals such as stromal cell-derived factor-1 acting on the MSC’s CXCR4 receptor.[5] However, this homing capacity is limited, and a substantial proportion of administered cells do not reach the intended target site.
Direct Intercellular Communication
Beyond paracrine signalling, MSCs can also communicate with damaged cells through tunnelling nanotubes. Allowing direct transfer of functional mitochondria into injured cells to restore their oxidative phosphorylation capacity. This has been demonstrated in osteoarthritic chondrocytes and is thought to be a distinct repair mechanism from vesicle-mediated paracrine signalling.[11]
Extracellular Vesicles and Exosomes
A growing body of research suggests that much of the therapeutic paracrine effect attributed to MSCs can be reproduced using the cell-free extracellular vesicles and exosomes that MSCs secrete. This has driven interest in cell-free products as a potentially safer and more standardisable alternative to whole-cell therapy.[9][12]
The video below shows an animation describing MSC’s, their differentiation potential and paracrine signalling mechanisms and discussing how MSCs regulate immune responses through cytokine modulation and support tissue repair.
Types of Stem Cells
Several categories of stem cell are used in current and emerging therapy, each with distinct properties and risk profiles. The table below summarises the main types.
| Type | Key features |
|---|---|
| Haematopoietic stem cells (HSCs) | Most established type; used for blood/immune reconstitution after chemotherapy or radiotherapy.[2] |
| Mesenchymal stem cells (MSCs) | Multipotent; sourced from bone marrow (BM-MSCs), adipose tissue (AT-MSCs), umbilical cord (UC-MSCs), placenta or dental pulp.[1][3]
Sources are not interchangeable: AT-MSCs favour adipogenic differentiation, BM-MSCs favour osteogenic differentiation, UC-MSCs show higher attachment/proliferation via CD146.[5] |
| Wharton’s jelly MSCs (WJ-MSCs) | Highest proliferative capacity and strongest immunomodulatory/neurotrophic profile among perinatal sources; non-invasive collection.[9] |
| Pluripotent stem cells; Embryonic stem cells (ESCs), Induced pluripotent stem cells (iPSCs) | Can differentiate into almost any cell type. Used in research for conditions such as macular degeneration, Parkinson’s disease and diabetes. PSCs carry a documented risk of teratoma (tumour) formation if undifferentiated cells persist, and their clinical use remains largely confined to trials.[2] |
| Extracellular vesicles/exosomes | Cell-free carriers of MSC signalling molecules; mostly preclinical, though human trials exist for lung disease and COVID-19 ARDS.[12][14] |
| Gene-edited MSCs | Clustered regularly interspaced short palindromic repeats (CRISPR) or CRISPR-associated protein 9 (Cas9) modified cells to reduce immune rejection or enhance signalling; early-stage research only.[6] |
Ethical note: ESCs require blastocyst destruction, a genuinely divisive issue with variable international regulation; iPSCs avoid this but carry tumorigenicity risk from reprogramming factors such as c-Myc (an oncogene that regulates cell growth, proliferation and division) .[15] Neither forms part of standard MSC-based practice.
Methods of Administration
The route of administration is chosen according to the target tissue and condition, and carries its own considerations and risks. The table below summarises the main routes in current use.
| Route | Use and considerations |
|---|---|
| Intravenous (IV) infusion | Used for systemic/immune conditions and increasingly explored for cardiovascular, respiratory and endocrine disease.[5]
Considerations: Cells are subject to rapid clearance in the spleen, lungs and other organs, which represents a substantial clinical challenge.[9] Risks: Cells could be trapped in lung capillaries, owing to their relative size compared with the capillary bed,[3][5] carrying embolism risk requiring filtration and monitoring protocols.[16] Although, a large real-world cohort (2,504 patients) found very low adverse event rates.[17] |
| Local/intra-articular injection | Cells are injected directly into a joint or area of tissue damage. Used in knee osteoarthritis and spinal disc degeneration trials.[18][19] |
| Intrathecal, Intradural and subarachnoid injection | Used for spinal cord injury and associated neuropathic pain, delivering cells directly into or around the spinal cord and cerebrospinal fluid. Trials using this route report good tolerability and safety, with variable and often modest functional benefit.[20] |
| Intralesional/intrafistula | Used for perianal fistulising Crohn’s disease.[2] |
| Scaffold-based implantation | Cells may be combined with biomaterial scaffolds to support localised tissue regeneration, an approach being developed for bone and cartilage repair, and also used experimentally in burns management via dermal matrix sheets.[2][5][21] |
The choice of administration route, dose, timing and frequency remains an active area of investigation, with no fully standardised protocol established across conditions.[2]
A caution on commercial marketing. IV MSC infusion for unapproved indications is marketed directly to patients by clinics internationally, including in well-regulated countries. Such material often does not distinguish between well-evidenced and speculative indications, and does not always distinguish between genuinely related products (for example, MSC infusion versus unrelated stem-cell-derived islet cell therapy).[16]
Physiotherapists should be ready to discuss the difference between an approved indication, an actively recruiting trial, and a commercially marketed but unapproved treatment.
Indications for Stem Cell Therapy Relevant to Physiotherapy
The table below summarises the main musculoskeletal and neurological applications and the current strength of evidence for each.
| Condition | Evidence summary | Key sources |
|---|---|---|
| Knee osteoarthritis | Rigorous blinded trials show limited benefit over placebo; broader reviews pooling mixed-quality studies report meaningful pain reduction, particularly with repeated dosing. | [4][11][18][22] |
| Osteoarthritis (OA) | 18-trial review found no standardised post-injection protocol and no use of graded eccentric loading | [23] |
| Spinal disc degeneration | Reduced pain/disability in pooled analyses, but mostly uncontrolled study designs | [19] |
| Rheumatoid arthritis, systemic lupus erythematosus (SLE), ankylosing spondylitis, Sjögren’s syndrome and systemic sclerosis | Reduced disease activity indices and inflammatory markers; UC-MSC trials report sustained improvement at 1–5 years, small samples | [3][10][11] |
| Tendon/soft tissue injury | Early interest in MSC-derived exosomes for plantar fasciitis | [24] |
| Bone healing | Functionalised MSCs investigated for fracture healing | [21] |
| Neuropathic pain | Mechanisms include axon regeneration, neurotrophic factor secretion and microglial modulation; spinal cord injury trials (intrathecal/intradural, n=10-11) report sensory improvement more consistently than motor recovery | [20] |
| Post-stroke regenerative strategies | WJ-MSCs show strong immunomodulatory/neurotrophic profile; however a large phase II/III trial found no benefit over control | [5][9] |
| Cerebral palsy | UC-MSCs improved gross motor function and cognition, peaking at 6 months | [5] |
| Frailty/sarcopenia | Only 3 small RCTs exist; inconsistent functional signals, no trial has used muscle-mass imaging outcomes | [25] |
Cultured versus uncultured preparations. A meta-analysis of 31 studies found cultured adipose-derived MSCs produce pain relief earlier (from 3 months) than uncultured stromal vascular fraction (12 months), though both converge by 12 months on function outcomes.[22]
Indications for Stem Cell Therapy Beyond Musculoskeletal and Neurological Practice
Physiotherapists in cardiorespiratory or oncology settings may encounter patients considering MSC therapy for the systemic conditions below.
| System | Evidence summary | Key sources |
|---|---|---|
| Cardiovascular: myocardial infarction, heart failure, chronic ischaemic cardiomyopathy, pulmonary hypertension | Mixed trial results (C-CURE positive, CHART-1 negative); UC-MSCs (RIMECARD, HUC-HEART) show promise for heart failure; no cardiac secretome/exosome trials yet exist | [5][10][26] |
| Respiratory: chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), bronchopulmonary dysplasia (BPD), idiopathic pulmonary fibrosis (IPF) | Bone marrow MSC trials for COPD largely unsuccessful; UC-MSCs show more promising early signals.
IV cells are trapped in the lungs first-pass, which some propose as therapeutically relevant. Multiple trials for COVID-19-related ARDS, reports reduced inflammatory markers and improved oxygenation; variation in dosing, timing and administration route across trials limits direct comparison. |
[5][27][28] [29][30] |
| Endocrine/metabolic: type 1 and type 2 diabetes mellitus | Safe but modest, often temporary improvement in C-peptide/HbA1c; autologous MSCs impaired in diabetic patients, favouring allogeneic donor cells | [5] [31] |
| Reproductive | Small trials/case reports for premature ovarian failure show improved follicular regeneration and live births; no UC- or adipose-MSC trials completed | [5] [32] |
| Burns and wound healing | Case series report faster healing and shorter hospital stays; bone marrow harvesting is invasive, so adipose-derived allogeneic cells are increasingly preferred; trial design remains weak | [5][33] |
Evidence for Stem Cell Therapy
The evidence base for MSC therapy shows a consistent pattern across conditions: a favourable safety profile set against considerable uncertainty over efficacy and standardisation. The table below sets out the main points on each side.
| Pros | Cons |
|---|---|
| Broad immunomodulatory mechanism with plausibility across many conditions.[3] | High-quality trials often show limited benefit; mixed results even in large cardiovascular trials.[5][18] |
| Generally favourable safety profile; low serious adverse event rates across large cohorts.[17][22] | Increased short-term joint pain/swelling versus placebo in osteoarthritis (risk ratio 1.58).[18] |
| Positive signals in disc degeneration, some rheumatic disease, and UC-MSC survival benefit in COVID-19 ARDS and Graft-versus-host disease (GVHD).[11][19] | Weak evidence base for neuropathic pain, reproductive disorders and burns; mostly small, uncontrolled studies.[5][20][32][33] |
| Autologous options reduce rejection risk; allogeneic cells are well tolerated without heavy immunosuppression.[1][5] | Significant heterogeneity in cell source, dose and culture method; potency assays vary between laboratories using identical source material.[1][5] |
| No genetic modification in standard use.[2] | Limited long-term safety data; isolated serious adverse events reported without established causal link.[3][22] |
| Pulmonary trapping and embolism risk after IV administration.[16] | |
| Infused products always contain some dead cells, which may exert their own immunomodulatory effect via phosphatidylserine release.[5] | |
| Regulatory and cost barriers; an estimated 700–1,000 unregulated clinics operate worldwide, with documented harms including tumour development.[15] |
Latest Developments in Stem Cell Therapy
Several emerging directions are shaping the next generation of stem cell therapy, summarised below.
Genetic Engineering
Researchers are using CRISPR-based gene editing to create “immune stealth” MSCs by knocking out genes such as β2-microglobulin, reducing immune recognition and potentially enabling more effective off-the-shelf, donor-derived products. Other applications include enhancing anti-inflammatory cytokine secretion (e.g. IL-10, TSG-6) and repurposing MSCs for anti-tumour immunotherapy by removing their immunosuppressive properties in the tumour microenvironment.[6]
Cell-free EV or Exosome Therapies
Isolated MSC-derived extracellular vesicles are being trialled as a way to deliver the same paracrine signalling benefits with a reduced risk profile, including lower theoretical risk of uncontrolled cell proliferation and markedly reduced pulmonary and hepatic entrapment compared with whole cells.[9] This approach is under preclinical investigation for:
- Post-stroke recovery [9]
- Plantar fasciitis [24]
- Neuropathic pain [20]
- Cardiac regeneration, though no clinical trials for cardiac secretome or exosome therapy specifically have yet been identified on major trial registries.[26]
- Preclinical animal work has demonstrated MSC-derived exosome effects in wound healing, bone defect repair and cartilage regeneration.[12]
Trial record for MSC-derived EVs and exosomes to date is concentrated overwhelmingly in lung disease and COVID-19-related respiratory failure, with musculoskeletal and cardiac applications still comparatively rare in registered trials.[14]
Biomaterial-enhanced MSCs
MSCs are increasingly being combined with scaffolds, growth factors or engineered surface modifications to improve bone regeneration outcomes and targeted tissue repair.[21]
Regenerative Rehabilitation
A growing body of work is examining how physiotherapy and structured rehabilitation protocols can be integrated with orthobiological treatments (PRP, Peptides, Stem Cell Therapy), including graded loading protocols following stem cell injection, to optimise outcomes.[23][34][35]
Application in new disease areas
Recent research is expanding MSC investigation into chronic kidney disease, haematopoietic recovery post-transplantation, and systemic conditions summarised above, reflecting the breadth of ongoing exploration.[20][25][36][37]
Dose optimisation research
A route-dependent effective dose window has been identified for EVs/exosomes:
- Nebulised administration achieved therapeutic effects at markedly lower particle doses than IV administration.[14]
- A proposed IL-6-linked dosing algorithm remains exploratory.[11][14]
Physiotherapy Management Following Stem Cell Therapy
No validated, condition-specific rehabilitation protocol exists.
A 2025 review of 16 osteoarthritis RCTs found only one used a documented physiotherapy programme,[35] and an 18-trial adipose-derived MSC review found no standardised protocol.[23]
The table below summarises the key studies underpinning current practice.
| Focus | Key finding | Study |
|---|---|---|
| Rehabilitation after adipose-derived stem cell injection, knee OA | No standardised protocol; no graded eccentric loading used in any trial | [23] |
| Physiotherapy after orthobiological injection | Only 1 of 16 RCTs used documented physiotherapy; guidance remains sparse | [35] |
| Regenerative rehabilitation concept | Mechanotherapy considered pivotal, but no standard human protocols exist | [38] |
| Mechanical loading in post-traumatic OA | Dynamic loading may benefit cartilage; optimal patterns undefined | [39] |
| Contextual effects of MSC injection | Substantial improvement may be placebo-related, not cellular | [20] |
Practice Guidance
Practice is currently guided by tissue-healing principles organised into three broad phases described in table below.[35]
| Inflammation (days 3–14) | Proliferation (days 3–14 onward) | Maturation (weeks 3–10) |
|---|---|---|
| Rest/short immobilisation for 24hrs | Gradual increase in range of motion and circulation | Progression to multi-joint, multi-plane movement |
| Elevation if possible | Water-based exercise | Eccentric strengthening |
| non-NSAID analgesia (NSAIDs may impair platelet function and reduce growth factor release) | Isometric before eccentric work | Proprioceptive and stability work |
| Small range-of-motion movement from day 1 | Pulsed electromagnetic field therapy (PEMF) shows added benefit in one trial. | Gradual increase in resistance and aerobic load |
A number of practical themes recur across the literature, even where formal protocols are lacking:
- Graded, phased loading is favoured over prolonged rest or early high-intensity loading.[38]
- Timing matters: in an animal model, early loading (1–3 weeks post-injury) reduced cartilage damage, while delayed loading (5–7 weeks) worsened it.[39]
- Individualised, precision-based rehabilitation is increasingly emphasised.[23]
- Contextual/placebo effects likely contribute meaningfully to reported improvement, reinforcing the value of realistic goal-setting.[20]
- For neuropathic pain following spinal cord injury, sensory improvement is more consistently reported than motor recovery, which should inform goal-setting.[20]
Physiotherapists should apply sound clinical reasoning grounded in tissue-healing principles, remain transparent about the limited evidence base, liaise closely with the treating physician regarding cell type and precautions, and frame goals realistically rather than presenting physiotherapy as “protecting” an unproven regenerative effect.[18][35]
Summary
The evidence reviewed points to several key conclusions about stem cell therapy as a whole and its place in physiotherapy practice:
- Stem cell therapy is a broad field, ranging from well-established haematopoietic stem cell transplantation for blood disorders, through MSCs.[2]
- MSC therapeutic effect is now understood to occur predominantly through paracrine signalling and immunomodulation, alongside more recently characterised mechanisms including inflammasome inhibition and direct mitochondrial transfer via tunnelling nanotubes.[1][9][11]
- Different stem cell types carry very different risk profiles.[1] Pluripotent stem cells carry a risk of tumour formation if not carefully controlled.[2] Embryonic stem cells raise ethical considerations related to their derivation.[15]
- The strength of evidence varies considerably by cell type, preparation method, condition and administration route.[3][4][5][20]
- A meaningful portion of reported improvement in musculoskeletal trials may be due to contextual/placebo effects rather than the cells themselves.[9][35]
- Standardisation of cell source, dosing and administration protocol remains unresolved across the field.[1][3][5][22]
- Physiotherapy following stem cell injection is widely considered important, but no validated, standardised rehabilitation protocol currently exists.[23][35][38]
The unregulated clinic sector poses a genuine risk to patients, and physiotherapists should be alert to the possibility that a patient’s treatment may not have been delivered under the same safety and evidentiary standards as those described in the clinical trial literature.[15]
Physiotherapists should support patients with realistic expectations, apply sound clinical reasoning where formal protocols are lacking, and stay alert to ongoing developments in cell-free extracellular vesicle therapies,[12][28] gene-edited cells,[6] and regenerative rehabilitation research as this rapidly evolving field matures.[34]
Resources
References
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 Han X, Liao R, Li X, et al. Mesenchymal stem cells in treating human diseases: molecular mechanisms and clinical studies. Sig Transduct Target Ther. 2025;10(1):262.
- ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 2.15 2.16 2.17 Chen S, Zhang L, Ren Y, et al. Clinical translational research on stem cell products: prospects and challenges. Sig Transduct Target Ther. 2026;11(1):178.
- ↑ 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 Hetta HF, Elsaghir A, Sijercic VC, et al. Clinical Progress in Mesenchymal Stem Cell Therapy: A Focus on Rheumatic Diseases. Immunity, Inflammation and Disease. 2025;13(5):e70189.
- ↑ 4.0 4.1 4.2 Goulian AJ, Goldstein B, Saad MA. Advancements in Regenerative Therapies for Orthopedics: A Comprehensive Review of Platelet-Rich Plasma, Mesenchymal Stem Cells, Peptide Therapies, and Biomimetic Applications. Journal of Clinical Medicine. 2025;14(6):2061.
- ↑ 5.00 5.01 5.02 5.03 5.04 5.05 5.06 5.07 5.08 5.09 5.10 5.11 5.12 5.13 5.14 5.15 5.16 5.17 5.18 5.19 5.20 5.21 Zhidu S, Ying T, Rui J, Chao Z. Translational potential of mesenchymal stem cells in regenerative therapies for human diseases: challenges and opportunities. Stem Cell Res Ther. 2024;15(1):266.
- ↑ 6.0 6.1 6.2 6.3 Dashti M, Mohammaddust Sarab M, Shad F, Dehnavi S. CRISPR-mediated engineering of mesenchymal stromal/stem cells: a summary of recent progress in immunological applications for regenerative medicine and cancer therapy. Stem Cell Res Ther. 2025;16(1):592.
- ↑ Etra A, Ferrara JLM, Levine JE. Remestemcel-L-rknd (Ryoncil): the first approved cellular therapy for steroid-refractory acute GVHD. Blood. 2025;146(16):1897-1901.
- ↑ Science ABC. Stem Cells: Explained in Simple Words. Available from: https://www.youtube.com/watch?v=MQXZ7cGZo1w [last accessed 7/09/2026]
- ↑ 9.00 9.01 9.02 9.03 9.04 9.05 9.06 9.07 9.08 9.09 9.10 9.11 Ganina A, Yerzhigit N, Lookin O, et al. Stem Cells in Post-Stroke Regenerative Therapy: Current Role of Wharton’s Jelly Mesenchymal Stem Cells in the Orchestrum. Brain Sciences. 2026;16(8):775.
- ↑ 10.0 10.1 10.2 Maldonado VV, Patel NH, Smith EE, et al. Clinical utility of mesenchymal stem/stromal cells in regenerative medicine and cellular therapy. J Biol Eng. 2023;17(1):44.
- ↑ 11.0 11.1 11.2 11.3 11.4 11.5 11.6 11.7 Yin L, Sun C yang, Chen G lai, et al. Modular mastery of inflammation: umbilical cord mesenchymal stem cells as a therapeutic frontier. Front Immunol. 2025;16.
- ↑ 12.0 12.1 12.2 12.3 Roszkowski S. Therapeutic potential of mesenchymal stem cell-derived exosomes for regenerative medicine applications. Clin Exp Med. 2024;24(1):46.
- ↑ Doctor Klioze. Mesenchymal Stem Cells. Available from: https://www.youtube.com/watch?v=g8FQOjlATgg [Last accessed 7/09/2026]
- ↑ 14.0 14.1 14.2 14.3 Wang Y, Zhu J, Ma Q, et al. Trends in mesenchymal stem cell-derived extracellular vesicles clinical trials 2014–2024: is efficacy optimal in a narrow dose range? Front Med. 2025;12.
- ↑ 15.0 15.1 15.2 15.3 Marei HE. Stem cell therapy: a revolutionary cure or a pandora’s box. Stem Cell Res Ther. 2025;16(1):255.
- ↑ 16.0 16.1 16.2 Terai S, Ezoe S, Mano K, et al. Recommendations for the safe implementation of intravenous administration of mesenchymal stromal cells. Regenerative Therapy. 2025;29:171-176.
- ↑ 17.0 17.1 Matsuoka T, Itohara T, Hara Y, Kobayashi N. Systematic Intravenous Administration of Autologous Mesenchymal Stem Cells Is Safe. Journal of Clinical Medicine. 2024;13(23):7460.
- ↑ 18.0 18.1 18.2 18.3 18.4 Sadeghirad B, Rehman Y, Khosravirad A, et al. Mesenchymal stem cells for chronic knee pain secondary to osteoarthritis: A systematic review and meta-analysis of randomized trials. Osteoarthritis and Cartilage. 2024;32(10):1207-1219.
- ↑ 19.0 19.1 19.2 Zhang W, Wang D, Li H, et al. Mesenchymal stem cells can improve discogenic pain in patients with intervertebral disc degeneration: a systematic review and meta-analysis. Front Bioeng Biotechnol. 2023;11.
- ↑ 20.0 20.1 20.2 20.3 20.4 20.5 20.6 20.7 20.8 Zhang WJ, Pi XW, Hu DX, Liu XP, Wu MM. Advances and challenges in cell therapy for neuropathic pain based on mesenchymal stem cells. Front Cell Dev Biol. 2025;13.
- ↑ 21.0 21.1 21.2 Huang W, Zhou C, Yu Y, et al. Functionalized mesenchymal stem cells for enhanced bone regeneration: advances and challenges. Stem Cell Res Ther. 2025;16(1):600.
- ↑ 22.0 22.1 22.2 22.3 22.4 Lee H, Lim Y, Lee SH. Rapid-acting pain relief in knee osteoarthritis: autologous-cultured adipose-derived mesenchymal stem cells outperform stromal vascular fraction: a systematic review and meta-analysis. Stem Cell Res Ther. 2024;15(1):446.
- ↑ 23.0 23.1 23.2 23.3 23.4 23.5 Panjaitan FY, Widyatmiko H, Ariyani FD, Rasyida AM, Hong M. Graded Eccentric Rehabilitation After Adipose-Derived Stem Cell Injection for Knee Osteoarthritis: A Systematic Review. Medicinus. 2026;15(3):139-150.
- ↑ 24.0 24.1 Liebmann K, Kimbrough DW, Best TM, Kouroupis D, Rodriguez Materon S. Plantar Fasciitis Pathophysiology and the Potential Role of Mesenchymal Stem Cell-Derived Extracellular Vesicles as Therapy. Biomedicines. 2025;13(7):1528.
- ↑ 25.0 25.1 Poutouri E, Sotiropoulou M, Potoupnis M, et al. Safety and Efficacy of Mesenchymal Stem Cell Therapy in Aging Frailty: A Systematic Review. International Journal of Molecular Sciences. 2026;27(17):7596.
- ↑ 26.0 26.1 Piotrowska P, Kraskiewicz H, Klimczak A. Mesenchymal Stem Cell Secretome for Cardiac Regeneration: Opportunity for Cell-Free Therapy. International Journal of Molecular Sciences. 2026;27(1):209.
- ↑ Le PTB, Pham PV. Mesenchymal stem cell therapy for chronic obstructive pulmonary disease: Mechanisms, clinical evidence, and therapeutic perspectives. Progress in Stem Cell. 2025;12(1):416-416.
- ↑ 28.0 28.1 Wang F, Xie C, Wang X. Mesenchymal stem cell therapies for ARDS: translational promise and challenges. Stem Cell Res Ther. 2025;16(1):504.
- ↑ Team PI. BPD drug pipeline: MSC therapy, IGF-1, TGF-β trends. Patsnap. April 21, 2026. Accessed September 8, 2026. https://www.patsnap.com/resources/blog/articles/bpd-drug-pipeline-msc-therapy-igf-1-tgf-β-trends/
- ↑ How MSCs Could Transform IPF Treatment | Stemedix. July 17, 2025. Accessed September 8, 2026. https://stemedix.com/innovations-in-pulmonary-care-how-mscs-could-transform-ipf-treatment/
- ↑ Huang X, Liu Y, Li Z, Lerman LO. Mesenchymal Stem/Stromal Cells Therapy for Metabolic Syndrome: Potential Clinical Application? Stem Cells. 2023;41(10):893-906.
- ↑ 32.0 32.1 Nair R, Agarwal P, Gadre MA, Vasanthan KS, Seetharam RN. Stem cell treatments for female reproductive disorders: a comprehensive review. J Ovarian Res. 2025;18(1):161.
- ↑ 33.0 33.1 Stepp J, Gallicchio VS. Treatment of Severe Burns using Stem Cell Therapy. Journal of Stem Cell Research. 2026;7(1). Accessed September 8, 2026.
- ↑ 34.0 34.1 Tan B, Zhang A, Yu L. Regenerative rehabilitation: Mechanisms, clinical applications, and translational challenges. Regenesis Repair Rehabilitation. 2025;1(4):1-5.
- ↑ 35.0 35.1 35.2 35.3 35.4 35.5 35.6 Kiseljak D, Franić M, Ivković A, Čulo I. Physiotherapy for Osteoarthritis Following Orthobiological Injections – a Narrative Review of Recent Literature. Croat nurs j (Online). 2025;9(1):141-150.
- ↑ Li J, Wu M, He L. Immunomodulatory effects of mesenchymal stem cell therapy in chronic kidney disease: a literature review. BMC Nephrol. 2025;26(1):107.
- ↑ Pouryazdanpanah N, Moazed V, Khalilabadi RM, Dehesh T, Farsinejad A. Mesenchymal stem cell infusion to accelerate hematopoietic recovery after transplantation: A comprehensive systematic review of clinical studies (2000–2025). Critical Reviews in Oncology/Hematology. 2025;215:104875.
- ↑ 38.0 38.1 38.2 Centeno CJ, Pastoriza SM. PAST, CURRENT AND FUTURE INTERVENTIONAL ORTHOBIOLOGICS TECHNIQUES AND HOW THEY RELATE TO REGENERATIVE REHABILITATION: A CLINICAL COMMENTARY. Int J Sports Phys Ther. 2020;15(2):301-325. Accessed September 5, 2026.
- ↑ 39.0 39.1 Gardashli M, Baron M, Huang C, et al. Mechanical loading and orthobiologic therapies in the treatment of post-traumatic osteoarthritis (PTOA): a comprehensive review. Front Bioeng Biotechnol. 2024;12.