Adipose-Derived Stem Cells Inhibit the Contractile Myofibroblast in Dupuytrenʼs Disease

Verhoekx, Jennifer S N; Mudera, Vivek; Walbeehm, Erik T.; Hovius, Steven E.R.

doi:10.1097/prs.0b013e3182a3bf2b

Cited by 47 publications

(36 citation statements)

References 42 publications

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“…SVFC transplantation has been associated with a reduction in fibrosis and improved regeneration in other tissue injury and disease models, such as liver injury [13], Peyronie's disease [14], myocardial infarctions [15], and Dupuytren's disease [16], and supports our finding of reduced fibrosis after rotator cuff tear. The mechanism behind the reduction in fibrosis following SVFC treatment in various tissues is unclear.…”

Section: Discussionsupporting

confidence: 78%

“…The mechanism behind the reduction in fibrosis following SVFC treatment in various tissues is unclear. SVFCs may act by inhibiting collagen synthesis and reducing the proliferation of fibroblasts either directly [16] or indirectly through the regulation of macrophages [17]. Combined with data from Oh and colleagues [18] that found SVFCs augment tendon to bone healing following rotator cuff repair, SVFC treatment in chronically torn rotator cuff muscles of patients may improve muscle quality, reduce fibrosis, and lead to a more stable repair.…”

Section: Discussionmentioning

confidence: 99%

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Stromal vascular stem cell treatment decreases muscle fibrosis following chronic rotator cuff tear

Gumucio

Flood

Roche

et al. 2015

International Orthopaedics (SICOT)

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PURPOSE Rotator cuff injuries are associated with atrophy and fat infiltration into the muscle, commonly referred to as "fatty degeneration." As the poor function of chronically torn muscles may limit recovery after surgical repair, there is considerable interest in finding therapies to enhance muscle regeneration. Stromal vascular stem cells (SVFCs) can improve muscle regeneration in other chronic injury states, and our objective was to evaluate the ability of SVFCs to reduce fibrosis and fat accumulation, and enhance muscle fiber specific force production after chronic rotator cuff tear. METHODS Chronic supraspinatus tears were induced in adult immunodeficient rats, and repaired one month following tear. Rats received vehicle control, or injections of 3×105 or 3×106 human SVFCs into supraspinatus muscles. RESULTS Two weeks following repair, we detected donor human DNA and protein in SVFC treated muscles. There was a 40% reduction in fibrosis in the treated groups compared to controls (p=0.03 for 3×105, p=0.04 for 3×106), and no differences between groups for lipid content or force production were observed. CONCLUSIONS As there has been much interest in the use of stem cell-based therapies in musculoskeletal regenerative medicine, the reduction in fibrosis and trend towards an improvement in single fiber contractility suggest that SVFCs may be beneficial to enhance the treatment and recovery of patients with chronic rotator cuff tears.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Stromal vascular stem cell treatment decreases muscle fibrosis following chronic rotator cuff tear

Gumucio

Flood

Roche

et al. 2015

International Orthopaedics (SICOT)

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“…By contrast, this matrix-modifying MSC activity may help to attenuate disease severity and ultimately contribute to useful muscle mass [137]. Harmful proliferation and contraction of myofibroblasts, as occurs in Dupuytren's contracture, may be attenuated in the presence of the CM of both AD-MSCs or BM-MSCs as well as the physical presence of AD-MSCs (but not BM-MSCs) [138]. BM-MSCs appear to contribute to pathological myofibroblast proliferation while AD-MSCs appear to inhibit the activity slightly [138].…”

Section: Muscles and Miscellanymentioning

confidence: 99%

Secreted trophic factors of mesenchymal stem cells support neurovascular and musculoskeletal therapies

2016

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Adult mesenchymal stem cells (MSCs) represent a subject of intense experimental and biomedical interest. Recently, trophic activities of MSCs have become the topic of a number of revealing studies that span both basic and clinical fields. In this review, we focus on recent investigations that have elucidated trophic mechanisms and shed light on MSC clinical efficacy relevant to musculoskeletal applications. Innate differences due to MSC sourcing may play a role in the clinical utility of isolated MSCs. Pain management, osteochondral, nerve, or blood vessel support by MSCs derived from both autologous and allogeneic sources have been examined. Recent mechanistic insights into the trophic activities of these cells point to ultimate regulation by nitric oxide, nuclear factor-kB, and indoleamine, among other signaling pathways. Classic growth factors and cytokines—such as VEGF, CNTF, GDNF, TGF-β, interleukins (IL-1β, IL-6, and IL-8), and C-C ligands (CCL-2, CCL-5, and CCL-23)—serve as paracrine control molecules secreted or packaged into extracellular vesicles, or exosomes, by MSCs. Recent studies have also implicated signaling by microRNAs contained in MSC-derived exosomes. The response of target cells is further regulated by their microenvironment, involving the extracellular matrix, which may be modified by MSC-produced matrix metalloproteinases (MMPs) and tissue inhibitor of MMPs. Trophic activities of MSCs, either resident or introduced exogenously, are thus intricately controlled, and may be further fine-tuned via implant material modifications. MSCs are actively being investigated for the repair and regeneration of both osteochondral and other musculoskeletal tissues, such as tendon/ligament and meniscus. Future rational and effective MSC-based musculoskeletal therapies will benefit from better mechanistic understanding of MSC trophic activities, for example using analytical “-omics” profiling approaches.

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“…A role for fat grafting in Dupuytren's disease is supported by the finding that the contractile function of the myofibroblast is inhibited by adipose derived stem cells. 29 Longer term data on this technique are awaited.…”

Section: Long Answermentioning

confidence: 99%

A hand flexion contracture with progression

McInerney

O’Shaughnessy

Clover

2014

BMJ

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Adipose-Derived Stem Cells Inhibit the Contractile Myofibroblast in Dupuytrenʼs Disease

Abstract: Adipose-derived stem cells inhibit the contractile myofibroblast in Dupuytren's disease, and these findings lend support to the potential benefit of lipografting in conjunction with aponeurotomy as a novel strategy for the treatment of Dupuytren's disease.

Cited by 47 publications

References 42 publications

Stromal vascular stem cell treatment decreases muscle fibrosis following chronic rotator cuff tear

Stromal vascular stem cell treatment decreases muscle fibrosis following chronic rotator cuff tear

Secreted trophic factors of mesenchymal stem cells support neurovascular and musculoskeletal therapies

A hand flexion contracture with progression

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