Use of stem cells and growth factors in rotator cuff tendon repair

Tsekes, Dimitrios; Κωνσταντόπουλος, Γεώργιος; Khan, Wasim; Rossouw, D. J.; Elvey, Mike; Singh, Jagwant

doi:10.1007/s00590-019-02366-x

Cited by 21 publications

(20 citation statements)

References 68 publications

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“…Some authors proposed bone marrow stimulation by drilling of holes into the proximal humerus at the footprint of arthroscopic rotator cuff repair [58][59][60]. However, the real benefit of these procedures in which mesenchymal stem cells (MSCs) may serve to augment arthroscopic rotator cuff repair rather than the only therapy has yet to be demonstrated (c.f [23].). The latter also applies to isolation of MSCs from the subacromial bursa, rotator cuff tendon, biceps tendon, or synovial fluid, respectively, as proposed by some authors (reviewed in [23]).…”

Section: Efficacy Of Treating Symptomatic Partial-thickness Rotator mentioning

confidence: 99%

“…Over the past decade, stem cell injection therapy has emerged as a promising treatment for many musculoskeletal conditions. In animal models, injections of adult stem cells isolated from adipose tissue into pathologic rotator cuff tissues has been shown to produce a number of beneficial effects, including decreased number of inflammatory cells, improved regeneration of tendons with less scarred healing, improved collagen fiber arrangement, higher load-to-failure, and higher tensile strength of the treated tendons [19][20][21][22][23]. However, corresponding clinical studies have not yet been reported.…”

Section: Introductionmentioning

confidence: 99%

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Safety and efficacy of treating symptomatic, partial-thickness rotator cuff tears with fresh, uncultured, unmodified, autologous adipose-derived regenerative cells (UA-ADRCs) isolated at the point of care: a prospective, randomized, controlled first-in-human pilot study

et al. 2020

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Background: This study tested the hypothesis that treatment of symptomatic, partial-thickness rotator cuff tears (sPTRCT) with fresh, uncultured, unmodified, autologous adipose-derived regenerative cells (UA-ADRCs) isolated from lipoaspirate at the point of care is safe and more effective than corticosteroid injection. Methods: Subjects aged between 30 and 75 years with sPTRCT who did not respond to physical therapy treatments for at least 6 weeks were randomly assigned to receive a single injection of an average 11.4 × 10 6 UA-ADRCs (in 5 mL liquid; mean cell viability: 88%) (n = 11; modified intention-to-treat (mITT) population) or a single injection of 80 mg of methylprednisolone (40 mg/mL; 2 mL) plus 3 mL of 0.25% bupivacaine (n = 5; mITT population), respectively. Safety and efficacy were assessed using the American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES), RAND Short Form-36 Health Survey, and pain visual analogue scale (VAS) at baseline (BL) as well as 3 weeks (W3), W6, W9, W12, W24, W32, W40, and W52 post treatment. Fat-saturated T2-weighted magnetic resonance imaging of the shoulder was performed at BL as well as at W24 and W52 post treatment.

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Section: Efficacy Of Treating Symptomatic Partial-thickness Rotator mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Safety and efficacy of treating symptomatic, partial-thickness rotator cuff tears with fresh, uncultured, unmodified, autologous adipose-derived regenerative cells (UA-ADRCs) isolated at the point of care: a prospective, randomized, controlled first-in-human pilot study

et al. 2020

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“…However, the real benefit of these procedures in which mesenchymal stem cells (MSCs) may serve to augment arthroscopic rotator cuff repair rather than the only therapy has yet to be demonstrated (c.f. [17]). The latter also applies to isolation of MSCs from the subacromial bursa, rotator cuff tendon, biceps tendon or synovial fluid, respectively, as proposed by some authors (reviewed in [17]).…”

Section: Efficacy Of Treating Symptomatic Partial-thickness Rotator mentioning

confidence: 99%

“…[17]). The latter also applies to isolation of MSCs from the subacromial bursa, rotator cuff tendon, biceps tendon or synovial fluid, respectively, as proposed by some authors (reviewed in [17]). To our knowledge, application of such MSCs in the management of PTRCT have not yet been reported.…”

Section: Efficacy Of Treating Symptomatic Partial-thickness Rotator mentioning

confidence: 99%

“…In animal models, injections of adult stem cells isolated from adipose tissue into pathologic rotator cuff tissues has been shown to produce a positive biological response. The reported beneficial effects included decreased number of inflammatory cells, improved regeneration of tendons with less scarred healing, improved collagen fiber arrangement, higher load-tofailure and higher tensile strength of the treated tendons [13][14][15][16][17]. However, corresponding clinical studies have not yet been reported.…”

Section: Introductionmentioning

confidence: 99%

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Safety and Efficacy of Treating Symptomatic, Partial-Thickness Rotator Cuff Tear with Fresh, Uncultured, Unmodified, Autologous Adipose Derived Regenerative Cells (UA-ADRCs) Isolated at Point of Care: A Prospective, Randomized, Controlled First-in-Human Pilot Study

Hurd¹,

Facile²,

Weiss³

et al. 2019

Preprint

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Background: This study tested the hypothesis that treatment of symptomatic, partial-thickness rotator cuff tear (sPTRCT) with fresh, uncultured, unmodified, autologous adipose derived regenerative cells (UA-ADRCs) isolated from lipoaspirate at point of care is safe and more effective than corticosteroid injection. Methods: Subjects aged between 30 and 75 years with sPTRCT who did not respond to traditional nonoperative care for at least six weeks were randomly assigned to receive a single injection of an average 11.4×106 UA-ADRCs (in 5 ml liquid; mean cell viability: 88%) (n=11; modified intention-to-treat (mITT) population) or a single injection of 80 mg of methylprednisolone (40 mg/ml; 2 ml) plus 3 ml of 0.25% bupivacaine (n=5; mITT population), respectively. Safety and efficacy were assessed using the American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES), RAND Short Form-36 Health Survey and pain visual analogue scale (VAS) at baseline (BL) as well as 3 weeks (W3), W6, W9, W12, W24, W32, W40 and W52 post treatment. Fat-saturated T2 weighted magnetic resonance imaging of the shoulder was performed at BL as well as at W24 and W52 post treatment. Results: No severe adverse events related to the injection of UA-ADRCs were observed in the twelve months post treatment. The risks connected with treatment of sPTRCT with UA-ADRCs were not greater than those connected with treatment of sPTRCT with corticosteroid injection. Subjects in the UA-ADRCs group showed statistically significantly higher mean ASES total scores at W24 and W52 post treatment than subjects in the corticosteroid group (p < 0.05). Discussion: Injection of fresh, uncultured, unmodified, autologous adipose derived regenerative cells is a safe and effective treatment of sPTRCT. Larger trials are needed to verify this result. Trial registration: Clinicaltrials.gov ID NCT02918136. Registered September 28, 2016. Level of evidence: Level I; prospective, randomized, controlled trial.

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Inhibition of Smad3 promotes the healing of rotator cuff injury in a rat model

Wang

Zhou

Liu

et al. 2020

Journal Orthopaedic Research

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To investigate the effect of inhibiting transforming growth factor-β (TGF-β1)/ Smad2/3 signaling on rotator cuff (RC) healing. A bilateral supraspinatus tendon detachment-repair model of Sprague-Dawley (SD) rats was utilized. A total of 120 SD rats were randomly assigned to six groups and each group received the subacromial injection of normal saline, empty vectors, or lentiviral vectors containing small interfering RNA against TGF-β1, Smad2, Smad3 at the bone-tendon junction. Biomechanical and histological analyses were performed to evaluate bone-tendon junction healing quality at 8 weeks after repair. Histologically, scar healing was found in all surgical groups. Animals with inhibited Smad3 exhibited better bonetendon junction structures with higher density, parallel orientation, and collagen fiber continuity than other surgical group animals. Immunohistochemistry revealed that the protein expression level of collagen I in animals with inhibited Smad3 was more prominent compared with all other surgical groups. Biomechanically, Animals with inhibited Smad3 showed better results in the maximum load at 4, 6, and 8 weeks after surgery compared with other surgical groups. Besides, C3H10T1/2 (Smad3−) cells increased TT-D6 cell migration and tendon-associated genes expression (scleraxis, tenascin C, collagen I) in coculture system. We conclude that inhibition of Smad3 promotes RC tendon healing in the rat supraspinatus model.

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Use of stem cells and growth factors in rotator cuff tendon repair

Cited by 21 publications

References 68 publications

Safety and efficacy of treating symptomatic, partial-thickness rotator cuff tears with fresh, uncultured, unmodified, autologous adipose-derived regenerative cells (UA-ADRCs) isolated at the point of care: a prospective, randomized, controlled first-in-human pilot study

Safety and efficacy of treating symptomatic, partial-thickness rotator cuff tears with fresh, uncultured, unmodified, autologous adipose-derived regenerative cells (UA-ADRCs) isolated at the point of care: a prospective, randomized, controlled first-in-human pilot study

Safety and Efficacy of Treating Symptomatic, Partial-Thickness Rotator Cuff Tear with Fresh, Uncultured, Unmodified, Autologous Adipose Derived Regenerative Cells (UA-ADRCs) Isolated at Point of Care: A Prospective, Randomized, Controlled First-in-Human Pilot Study

Inhibition of Smad3 promotes the healing of rotator cuff injury in a rat model

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