Annals of Rehabilitation Medicine

"Stem cell"

Original Articles

Pain & Musculoskeletal rehabilitation

Mesenchymal Stem Cells Use in the Treatment of Tendon Disorders: A Systematic Review and Meta-Analysis of Prospective Clinical Studies: Woo Sup Cho, Sun Gun Chung, Won Kim, Chris H. Jo, Shi-Uk Lee, Sang Yoon Lee; Ann Rehabil Med 2021;45(4):274-283. Published online August 30, 2021; DOI: https://doi.org/10.5535/arm.21078; Correction in: Ann Rehabil Med 2021;45(5):410

Objective
To evaluate the efficacy and safety of mesenchymal stem cells (MSCs) therapy in patients with tendon disorders enrolled in prospective clinical studies.
Methods
We systematically searched prospective clinical studies that investigated the effects of MSC administration on human tendon disorders with at least a 6-month follow-up period in the PubMed-MEDLINE, EMBASE, and Cochrane Library databases. The primary outcome of interest was the change in pain on motion related to tendon disorders. Meta-regression analyses were performed to assess the relationship between MSC dose and pooled effect sizes in each cell dose.
Results
Four prospective clinical trials that investigated the effect of MSCs on tendon disorders were retrieved. MSCs showed a significant pooled effect size (overall Hedges’ g pooled standardized mean difference=1.868; 95% confidence interval, 1.274–2.462; p<0.001). The treatment with MSCs improved all the aspects analyzed, namely pain, functional scores, radiological parameters (magnetic resonance image or ultrasonography), and arthroscopic findings. In the meta-regression analysis, a significant cell dose-dependent response in pain relief (Q=9.06, p=0.029) was observed.
Conclusion
Our meta-analysis revealed that MSC therapy may improve pain, function, radiological, and arthroscopic parameters in patients with tendon disorders. A strong need for large-scale randomized controlled trials has emerged to confirm the long-term functional improvement and adverse effects of MSC therapies in tendon disorders.

Citations

Citations to this article as recorded by

Mesenchymal stem cell-derived extracellular vesicles in musculoskeletal regeneration: mechanisms, applications, and future prospects
Fatemeh Aziziyan, Shiva Sarani Asl, Mohammadreza Mahdipour, Rahil Nasari Fard, Mohsen Sheykhhasan
Stem Cell Research & Therapy.2026;[Epub] CrossRef
Controlled TPCA-1 delivery engineers a pro-tenogenic niche to initiate tendon regeneration by targeting IKKβ/NF-κB signaling
Jialin Chen, Renwang Sheng, Qingyun Mo, Ludvig J. Backman, Zhiyuan Lu, Qiuzi Long, Zhixuan Chen, Zhicheng Cao, Yanan Zhang, Chuanquan Liu, Haotian Zheng, Yu Qi, Mumin Cao, Yunfeng Rui, Wei Zhang
Bioactive Materials.2025; 44: 319. CrossRef
The role of injections of mesenchymal stem cells as an augmentation tool in rotator cuff repair: a systematic review
Nuno Vieira Ferreira, Renato Andrade, Tânia Pinto Freitas, Clara de Campos Azevedo, João Espregueira-Mendes, António J. Salgado, Nuno Sevivas
JSES Reviews, Reports, and Techniques.2025; 5(2): 231. CrossRef
Therapeutic Potential of Mesenchymal Stem Cell and Tenocyte Secretomes for Tendon Repair: Proteomic Profiling and Functional Characterization In Vitro and In Ovo
Petra Wolint, Iris Miescher, Asma Mechakra, Patrick Jäger, Julia Rieber, Maurizio Calcagni, Pietro Giovanoli, Viola Vogel, Jess G. Snedeker, Johanna Buschmann
International Journal of Molecular Sciences.2025; 26(8): 3622. CrossRef
Effects of Transcatheter Arterial Embolization for Chronic Intractable Shoulder Pain: A Prospective Clinical Study
Kun Yung Kim, Young-Min Han, Myoung-Hwan Ko, Jeong-Hwan Seo, Sung-Hee Park, Yu Hui Won, Gi-Wook Kim, Tun-Chieh Chen
International Journal of Clinical Practice.2025;[Epub] CrossRef
Poor consideration of tissue loading in randomised trials of MSC interventions for tendon pathology: A systematic review using the TIDieR framework
Ben Dyck, Chris Clifford, Gordon J. Hendry, Graeme P. Hopper, David F. Hamilton
Journal of Experimental Orthopaedics.2025;[Epub] CrossRef
Mesenchymal Stromal Cells for the Enhancement of Surgical Flexor Tendon Repair in Animal Models: A Systematic Review and Meta-Analysis
Ilias Ektor Epanomeritakis, Andreas Eleftheriou, Anna Economou, Victor Lu, Wasim Khan
Bioengineering.2024; 11(7): 656. CrossRef
Reliable Fabrication of Mineral‐Graded Scaffolds by Spin‐Coating and Laser Machining for Use in Tendon‐to‐Bone Insertion Repair
Yidan Chen, Min Hao, Ismael Bousso, Stavros Thomopoulos, Younan Xia
Advanced Healthcare Materials.2024;[Epub] CrossRef
Insights into Hip pain using Hip X-ray: Epidemiological study of 8,898,044 Koreans
Taewook Kim, Yoonhee Kim, Woosup Cho
Scientific Reports.2024;[Epub] CrossRef
Evidence-based orthobiologic practice: Current evidence review and future directions
Madhan Jeyaraman, Naveen Jeyaraman, Swaminathan Ramasubramanian, Sangeetha Balaji, Sathish Muthu
World Journal of Orthopedics.2024; 15(10): 908. CrossRef
Regenerative Inflammation: The Mechanism Explained from the Perspective of Buffy-Coat Protagonism and Macrophage Polarization
Rubens Andrade Martins, Fábio Ramos Costa, Luyddy Pires, Márcia Santos, Gabriel Silva Santos, João Vitor Lana, Bruno Ramos Costa, Napoliane Santos, Alex Pontes de Macedo, André Kruel, José Fábio Lana
International Journal of Molecular Sciences.2024; 25(20): 11329. CrossRef
Optimizing repair of tendon ruptures and chronic tendinopathies: Integrating the use of biomarkers with biological interventions to improve patient outcomes and clinical trial design
David A. Hart, Aisha S. Ahmed, Paul Ackermann
Frontiers in Sports and Active Living.2023;[Epub] CrossRef
Patellar Tendinopathy: Diagnosis and Management
Shane M. A. Drakes
Current Physical Medicine and Rehabilitation Reports.2023; 11(3): 344. CrossRef
Editorial Commentary: Tendon-Derived Stem Cells Are in the Rotator Cuff Remnant and Decline With Age and Tear Chronicity—But the Clinical Relevance Is Not Known
Erik Hohmann
Arthroscopy: The Journal of Arthroscopic & Related Surgery.2022; 38(4): 1049. CrossRef
Is cellular therapy beneficial in management of rotator cuff tears? Meta-analysis of comparative clinical studies
Sathish Muthu, Cheruku Mogulesh, Vibhu Krishnan Viswanathan, Naveen Jeyaraman, Satvik N Pai, Madhan Jeyaraman, Manish Khanna
World Journal of Meta-Analysis.2022; 10(3): 162. CrossRef
Behandlung von Sehnenrupturen mit Stammzellen: eine aktuelle Übersicht
Christoph Schmitz, Tobias Würfel, Christopher Alt, Eckhard U. Alt
Obere Extremität.2022; 17(3): 141. CrossRef
Interleukin-1β in tendon injury enhances reparative gene and protein expression in mesenchymal stem cells
Drew W. Koch, Alix K. Berglund, Kristen M. Messenger, Jessica M. Gilbertie, Ilene M. Ellis, Lauren V. Schnabel
Frontiers in Veterinary Science.2022;[Epub] CrossRef
Cell therapy efficacy and safety in treating tendon disorders: a systemic review of clinical studies
Seyed Peyman Mirghaderi, Zahra Valizadeh, Kimia Shadman, Thibault Lafosse, Leila Oryadi‐Zanjani, Mir Saeed Yekaninejad, Mohammad Hossein Nabian
Journal of Experimental Orthopaedics.2022;[Epub] CrossRef

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Effect of Intravenous Infusion of G-CSF-Mobilized Peripheral Blood Mononuclear Cells on Upper Extremity Function in Cerebral Palsy Children: Kyeong Il Park, Young-Ho Lee, Wee-Jin Rah, Seung Hwi Jo, Si-Bog Park, Seung Hoon Han, Hani Koh, Jin Young Suh, Jang soo Um, Eun Hye Choi, Un Jin Park, Mi Jung Kim; Ann Rehabil Med 2017;41(1):113-120. Published online February 28, 2017; DOI: https://doi.org/10.5535/arm.2017.41.1.113

Abstract
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Objective

To investigate the effect of intravenous infusion of peripheral blood mononuclear cells (mPBMC) mobilized by granulocyte-colony stimulating factor (G-CSF) on upper extremity function in children with cerebral palsy (CP).

Methods

Fifty-seven children with CP were enrolled. Ten patients were excluded due to follow-up loss. In total, 47 patients (30 males and 17 females) were analyzed. All patients' parents provided signed consent before the start of the study. After administration of G-CSF for 5 days, mPBMC was collected and cryopreserved. Patients were randomized into two groups 1 month later. Twenty-two patients were administered mPBMC and 25 patients received normal saline as placebo. Six months later, the two groups were switched, and administered mPBMC and placebo, respectively. Quality of Upper Extremity Skills Test (QUEST) and the Manual Ability Classification System (MACS) were used to evaluate upper motor function.

Results

All subdomain and total scores of QUEST were significantly improved after mPBMC and placebo infusion, without significant differences between mPBMC and placebo groups. A month after G-CSF, all subdomain and total scores of QUEST were improved. The level of MACS remained unchanged in both mPBMC and placebo groups.

Conclusion

In this study, intravenously infused mPBMC showed no significant effect on upper extremity function in children with CP, as compared to placebo. The effect of mPBMC was likely masked by the effect of G-CSF, which was used in both groups and/or G-CSF itself might have other neurotrophic potentials in children with CP.

Citations

Citations to this article as recorded by

Clinical results of neurorestorative cell therapies and therapeutic indications according to cellular bio-proprieties
Hongyun Huang, Paul R. Sanberg, Gustavo A. Moviglia, Alok Sharma, Lin Chen, Di Chen
Regenerative Therapy.2023; 23: 52. CrossRef
Neurorestoratology: New Advances in Clinical Therapy
Hongyun Huang, Hari Shanker Sharma, Lin Chen, Di Chen
CNS & Neurological Disorders - Drug Targets.2023; 22(7): 1031. CrossRef
Microglia and Stem-Cell Mediated Neuroprotection after Neonatal Hypoxia-Ischemia
Catherine Brégère, Bernd Schwendele, Boris Radanovic, Raphael Guzman
Stem Cell Reviews and Reports.2022; 18(2): 474. CrossRef
State of the Evidence Traffic Lights 2019: Systematic Review of Interventions for Preventing and Treating Children with Cerebral Palsy
Iona Novak, Catherine Morgan, Michael Fahey, Megan Finch-Edmondson, Claire Galea, Ashleigh Hines, Katherine Langdon, Maria Mc Namara, Madison CB Paton, Himanshu Popat, Benjamin Shore, Amanda Khamis, Emma Stanton, Olivia P Finemore, Alice Tricks, Anna te V
Current Neurology and Neuroscience Reports.2020;[Epub] CrossRef
Clinical neurorestorative cell therapies: Developmental process, current state and future prospective
Hongyun Huang, Lin Chen, Gengsheng Mao, Hari Shanker Sharma
Journal of Neurorestoratology.2020; 8(2): 61. CrossRef
Improvement in gross motor function and muscle tone in children with cerebral palsy related to neonatal icterus: an open-label, uncontrolled clinical trial
Liem Nguyen Thanh, Kien Nguyen Trung, Chinh Vu Duy, Doan Ngo Van, Phuong Nguyen Hoang, Anh Nguyen Thi Phuong, Minh Duy Ngo, Thinh Nguyen Thi, Anh Bui Viet
BMC Pediatrics.2019;[Epub] CrossRef
Granulocyte colony-stimulating factor potential use in the treatment of children with cerebral palsy
G. Paszko-Patej, D. Sienkiewicz, B. Okurowska-Zawada, W. Kułak
Progress in Health Sciences.2017;[Epub] CrossRef

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Magnetic Resonance Spectroscopy Findings According to the Route of Injecting Stem Cells in Experimental Traumatic Brain Injured Rats.: Han, Eun Young , Chun, Min Ho , Lim, Dong pyo , Kim, Sang Tae; J Korean Acad Rehabil Med 2011;35(2):165-173.

Abstract
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Objective
To identify the effective injection route for adult human bone marrow stromal cells into traumatic brain injured rats. Method The TBI rats were created by the lateral percussion model (HD1700, Dragonfly, Silver Spring, USA). Eight rats without stem cell transplantation were assigned to a control group. We performed adult human bone marrow stromal cell transplantation into the contralateral hemisphere (n=7), the ipsilateral brain lesion (n=8) and via a tail vein (n=11), respectively, at 24 hours after brain injury. For all of the groups, MRS (magnetic resonance spectroscopy) study, behavior tests, rotarod tests and Barnes maze tests were conducted on day 1, day 7, day 42 and day 84. Sixteen rats were randomly assigned and were sacrificed for immunohistochemical staining. Results At day 42 (p=0.048) and day 84 (p=0.031) after TBI, the ratio of N-acetylaspartate to creatine (NAA/Cr) of the ipsilateral hemisphere was decreased in the control group, as assessed by MRS, whereas the ratio was increased in the other groups. On the post hoc analysis, significant differences were obtained among the intravenous group and the control group for the NAA/Cr ratio of the ipsilateral hemisphere at day 84 after TBI (p=0.050). However, there was no significant improvement on the behavior test, the rotarod test and the Barnes maze test. The cells were positively stained with antibodies to MAB-1281 and to GFAP. Conclusion We confirmed that adult human bone marrow stromal cell transplantation induced an increase of the NAA/Cr ratio of the ipsilateral hemisphere at day 84 in the intravenous group. Therefore, we suggest the intravenous route is more effective for mesenchymal stem cell transplantation.

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Myogenic Differentiation of Human Adipose-Derived Stem Cells.: Park, Yoon Ghil , Baek, Ah Mi , Do, Byung Rok , Choi, Jung Hwa , Kim, Sun Do; J Korean Acad Rehabil Med 2011;35(1):8-13.

Abstract
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Objective
Cell therapy has been extensively studied as a gene complementation approach in muscular dystrophy including Duchenne muscular dystrophy (DMD), and adipose tissue has recently been identified as a uniquely abundant and adequately accessible source of pluripotent cells. In the present work, we investigated myogenic potentials of adipose-derived stem cells (ADSCs) depending on culture media and isolation with using surface markers. Method Human ADSCs were obtained by liposuction and cultured in two different media; control and myogenic media. In addition we attempted to isolate ADSCs by utilizing surface markers: CD45 and CD133. The following observations were made to evaluate myogenic differentiation as the expression of myogenic regulatory factors (MyoD, Myf-5 and Myf-6) and desmin by RT-PCR and immunoflurescence study. Results Conversion of ADSCs to myogenic phenotype was observed by indirect immunoflurescence study of MyoD and Myf-5 in regardless of media type and isolation method. In addition mRNA of MyoD and Myf-5 were positive in both culture media, and there were no differences of MyoD and Myf-5 responses between CD45− and CD45−CD133− ADSCs. However, secondary myogenic regulatory factor (Myf-6) was not expressed constantly, and desmin were negative in all cultural condition. Conclusion Our findings suggest that human ADSCs might have myogenic potentials. However, further studies are needed to express the secondary myogenic regulatory factors and proteins in myoblasts.

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Human Mesenchymal Stem Cells Derived from Bone Marrow in Traumatic Brain Injury of Rat Migrate to the Site of Injury.: Kang, Si Hyun , Chun, Min Ho , Kim, Sang Tae , Cho, Hee Jin; J Korean Acad Rehabil Med 2009;33(5):520-526.

Abstract
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Objective
To define the migration and differentiation of adult human mesenchymal stem cells (hMSCs) derived from bone marrow, and their effect on neurobehavioral and cognitive improvements, after traumatic brain injury (TBI) in rats. Method: Two days after TBI, 1×106 hMSCs were injected into the corpus callosum of fifteen rats, on the contralateral side of TBI. Eleven rats received sham-operation as a control group. Neurobehavioral and Barnes maze tests, and magnetic resonance spectroscopy (MRS) were performed on days 1 and 28 after TBI. Immunohistochemical staining was performed to evaluate distribution and differentiation of hMSCs on day 56. Results: After 28 days, scores on the neurobehavioral test, Barnes maze test, and magnetic resonance spectroscopy (MRS) were higher than on day 1 in both the stem-cell and control groups, but there were no between-group differences. On day 56, injected hMSCs stained positively with MAB- 1281 were distributed in ipsilateral corpus callosum, lesion boundary zone, parietal cortex, and thalamic area around the lateral ventricle. Conclusion: hMSCs injected to the contralateral side of TBI survive and migrate to various areas of the ipsilateral hemisphere. We observed no neurobehavioral or cognitive improvements in test animals, indicating the need to adjust experimental methodologies including the development of appropriate tests to evaluate neurobehavioral and cognitive functions of rats. (J Korean Acad Rehab Med 2009; 33: 520-526)

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Effects of Transplantation of Human Embryonic Stem Cellson Functional Recovery in Spinal Cord Injured Rats.: Jung, Kwang Ik , Park, Chang Il , Park, Eun Sook , Shin, Ji Cheol; J Korean Acad Rehabil Med 2008;32(5):491-500.

Abstract
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Objective: To investigate the functional recovery following the transplantation of human embryonic stem (hES) cells into an injured rat spinal cord. Method: Sprague-Dawley rats were subjected to the spinal cord injury (SCI) using the New York University impactor. The rats were randomly allocated into three groups of 12 rats each, one media-treated and two hES cell-transplanted groups (5×10³/5Ռl, 2×10⁴/5Ռl). The hES cells were transplanted 1 week after a SCI. Results: The hES cells transplanted into the rats were found to promote the hind limb performance 8 weeks after transplantation. In the electrophysiological study, the transplanted rats showed significantly shortened latencies and increased amplitudes of motor and somatosensory evoked potentials, compared to the media-treated rats. In the spinal cord of the hES cell-treated group, the pathological findings including the glial scar formation and degenerative changes were attenuated and the human Tau protein-positive cells were identified in the vicinity of the necrotic cavity and in the white matter. Conclusion: These results suggest that the transplantation of hES cells might play a role in promoting the functional recovery after a SCI. (J Korean Acad Rehab Med 2008; 32: 491-500)

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The Effects of Human Adipose Tissue Derived Mesenchymal Stem Cells on Degenerative Change of Disc in Rabbit Model.: Kim, Sang Beom , Kwak, Hyun , Yoon, Kisung , Lee, Kyeong Woo , Park, Ji Hoon , Kwon, Yong Seok , Han, Jin Yeong , Jeong, Jin Sook , Lee, Jong Hwa; J Korean Acad Rehabil Med 2007;31(3):269-277.

Abstract
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Objective
To determine whether transplanted human adipose tissue derived stem cells (hATSCs) can survive and increase the amount of proteoglycans in degenerated intervertebral disc. Method: Lumbar disc degeneration was induced in thirty New Zealand white rabbits by injection of chondroitinase ABC^Ⱂ. After 2 weeks, hATSCs were transplanted in degenerated disc in hATSCs group. Control group received phosphate buffered saline. The histologic grading and height of disc were measured at 2, 4, and 8 weeks after transplantation. The viability of donor cells was identified by using β-Actin gene polymerase chain reaction (PCR). Results: 4 and 8 weeks after hATSCs transplantation, the histologic grading showed significantly high score in hATSCs group (p＜0.05), but the amount of proteoglycans was not significantly different between the two groups. The change of disc height was not significantly increased in hATSCs group. In the β-Actin gene PCR analysis, positive signal in the hATSCs group was observed. Conclusion: hATSCs transplantation may be useful in decelerating disc degeneration in experimental models and provide new hopes for treatment of degenerative disc disease in humans. (J Korean Acad Rehab Med 2007; 31: 269-277)