Library - Sport injury

Expert Opin Biol Ther. 2015;15(9):1285-92. doi: 10.1517/14712598.2015.1053867. Epub 2015 Jun 3.

Adipose-derived stem cells for wound repair and regeneration.

Shingyochi Y1Orbay HMizuno H.

Author information

1Juntendo University School of Medicine, Department of Plastic and Reconstructive Surgery , 2-1-1 Hongo Bunkyo-ku, Tokyo 1138421 , Japan.

Abstract

INTRODUCTION:

The use of undifferentiated cells for cell-based tissue repair and regeneration strategies represents a promising approach for chronic wound healing. Multipotent adult stem cells isolated from adipose tissue, termed adipose-derived stem cells (ASCs), appear to be an ideal population of stem cells because they are autologous, non-immunogenic, plentiful, and easily obtained. Both preclinical and clinical studies have revealed that ASCs have potential for wound healing due to the mechanisms described below.

AREAS COVERED:

Both in vitro and in vivo studies demonstrated that ASCs not only differentiate into keratinocytes, fibroblasts, and endothelial cells, as evidenced by their morphology, expression of cell surface markers, and gene expression, but also secrete several soluble factors, which positively contribute to wound healing in a paracrine manner. Clinical trials have been conducted using autologous ASCs with great success.

EXPERT OPINION:

There remain many concerns regarding the use of ASCs, including how these cells act as precursors of keratinocytes, fibroblasts, and endothelial cells, or as a secretion vehicle of soluble factors. Further studies are necessary to establish the optimal strategy for the treatment of chronic wounds in patients with different disease backgrounds.

KEYWORDS:

adipose-derived stem cells; clinical trials; growth factors; regeneration; wound healing

Ann Plast Surg. 2011 Feb;66(2):210-5. doi: 10.1097/SAP.0b013e3181e6d06c.

Adipose-derived stem cells for wound healing applications.

Cherubino M1Rubin JPMiljkovic NKelmendi-Doko AMarra KG.

Author information

1Division of Plastic Surgery, Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA.

Abstract

Nonhealing wounds remain a significant challenge for plastic surgeons. More than 600,000 people suffer from venous ulcers and 1.5 to 3 million people are being treated for pressure sores every year in the United States. The use of tissue engineering techniques such as stem-cell therapy and gene therapy to improve wound healing is a promising strategy. Adipose tissue represents a source of cells that may be able to enhance wound healing. Adipose-derived stem cells (ASCs) are adult stem cells that are easily harvested and of great interest for plastic surgeons. Specifically, ASCs secrete angiogenic growth factors that can induce tissue regeneration. This review describes innovative research strategies using ASCs therapies for treatment of chronic, nonhealing wounds.

Expert Opin Biol Ther. 2015;15(9):1285-92. doi: 10.1517/14712598.2015.1053867. Epub 2015 Jun 3.

Adipose-derived stem cells for wound repair and regeneration.

Shingyochi Y1Orbay HMizuno H.

Author information

1Juntendo University School of Medicine, Department of Plastic and Reconstructive Surgery , 2-1-1 Hongo Bunkyo-ku, Tokyo 1138421 , Japan.

Abstract

INTRODUCTION:

The use of undifferentiated cells for cell-based tissue repair and regeneration strategies represents a promising approach for chronic wound healing. Multipotent adult stem cells isolated from adipose tissue, termed adipose-derived stem cells (ASCs), appear to be an ideal population of stem cells because they are autologous, non-immunogenic, plentiful, and easily obtained. Both preclinical and clinical studies have revealed that ASCs have potential for wound healing due to the mechanisms described below.

AREAS COVERED:

Both in vitro and in vivo studies demonstrated that ASCs not only differentiate into keratinocytes, fibroblasts, and endothelial cells, as evidenced by their morphology, expression of cell surface markers, and gene expression, but also secrete several soluble factors, which positively contribute to wound healing in a paracrine manner. Clinical trials have been conducted using autologous ASCs with great success.

EXPERT OPINION:

There remain many concerns regarding the use of ASCs, including how these cells act as precursors of keratinocytes, fibroblasts, and endothelial cells, or as a secretion vehicle of soluble factors. Further studies are necessary to establish the optimal strategy for the treatment of chronic wounds in patients with different disease backgrounds.

KEYWORDS:

adipose-derived stem cells; clinical trials; growth factors; regeneration; wound healing

Orthopaedic Journal of Sports Medicine. 2016 Jul 18. doi: 10.1177/2325967116S00128

Treatment of Achilles Tendinopathy with Autologous Adipose-derived Stromal Vascular Fraction: Results of a Randomized Prospective Clinical Trial

de Girolamo L1, Grassi M, Vigano M, Orfei CP, Montrasio UA, Usuelli F.

Author information

1Galeazzi Orthopaedic Institute, Milan, Italy.

Abstract

Objectives: Achilles tendinopathy commonly occurs in both active and inactive persons. It consists in the development of pain and inflammation in the early phases, with progression to the development of fibrotic tissue and degeneration of tendon matrix. Current conservative treatment approaches do not provide sustained satisfactory results, particularly in active patients, although platelet rich plasma (PRP) injection have shown to be effective in many cases. The therapeutic effect of adipose-derived mesenchymal stem cells (ASCs), either expanded or used directly within the stromal vascular fraction (SVF), have demonstrated to possess significant antiinflammatory and immunomodulatory effects, mediated by the release of active factors, and thus potentially useful in the treatment of tendinopathy.

Methods: Patients affected by non-insertional Achilles tendinopathy (range 18-55 y/o) were prospectively enrolled in this controlled study, and randomly assigned either to single PRP injection group (GPSIII kit, Biomet, USA) (n=28 tendons) or single adipose tissue SVF (FastKit, Corios, Italy) (n=28 tendons) injection group. All patients were assessed clinically pre-operatively and at 15, 30, 60, 120 and 180 days from treatment, using VAS Pain, VISA-A, AOFAS and SF-36 forms. Patients also underwent to US and MRI before treatment and then at 4 and 6 monthfollow-ups. An aliquot of SVF of each patient was analyzed in vitro for mesenchymal stem cells (MSC) content, viability, proliferation rate, differentiation potential and immunomodulatory ability. Sample size of the study was calculated with a power analysis based on VISA-A score. All the results are expressed as mean ± standard deviation. A Wilcoxon test for paired data was performed to compare variables before and after surgery.

Results: Population background data and pre-operative scores were similar in the two groups (p>0.05). At final follow up both patients group showed significantly improvements in all the scores in comparison to baseline (p<0.05). In SVF patients these improvements were faster, with significantly better scores with respect to preinjection level already starting 15 days after treatment. Indeed at this time point a significant difference between groups in term of VAS, AOFAS and VISA-A score was observed (p<0.05), with better results in the SVF group. After 6 months MR and ultrasounds showed an improvement of clinical signs in both groups, without relevant differences. No side effects were observed in neither groups. In vitro analysis showed a modest content of MSCs in the SVF samples; however these cells were able to efficiently proliferate and differentiate, and to exert good immunomodulatory effect in an in vitro inflammatory model.

Conclusion: Both PRP and SVF are safe and effective treatments for Achilles tendinopathy. However, SVF allowed to obtain faster results, thus allowing to consider this treatment particularly suitable for patients requiring to come back to physical activities sooner.

Sports Med. 2016 Sep 28. doi: 10.1007/s40279-016-0620-z

Biological Therapies in Regenerative Sports Medicine

Andia I1, Maffulli N2,3.

Author information

1Regenerative Medicine Laboratory, BioCruces Health Research Institute, Cruces University Hospital, Pza Cruces 12, 48903 Barakaldo, Spain

2Department of Musculoskeletal Disorders, University of Salerno School of Medicine and Dentistry, Salerno, Italy

3Queen Mary University of London, Barts and the London School of Medicine and Dentistry Centre for Sports and Exercise Medicine, Mile End Hospital, 275 Bancroft Road, London E1 4DG, England

Abstract

Regenerative medicine seeks to harness the potential of cell biology for tissue replacement therapies, which will restore lost tissue functionality. Controlling and enhancing tissue healing is not just a matter of cells, but also of molecules and mechanical forces. We first describe the main biological technologies to boost musculoskeletal healing, including bone marrow and subcutaneous fatderived regenerative products, as well as platelet-rich plasma and conditioned media. We provide some information describing possible mechanisms of action. We performed a literature search up to January 2016 searching for clinical outcomes following the use of cell therapies for sports conditions, tendons, and joints. The safety and effi- cacy of cell therapies for tendon conditions was examined in nine studies involving undifferentiated and differentiated (skin fibroblasts, tenocytes) cells. A total of 54 studies investigated the effects of mesenchymal stem-cell (MSC) products for joint conditions including anterior cruciate ligament, meniscus, and chondral lesions as well as osteoarthritis. In 22 studies, cellular products were injected intra-articularly, whereas in 32 studies MSC products were implanted during surgical/arthroscopic procedures. The heterogeneity of clinical conditions, cellular products, and approaches for delivery/implantation make comparability difficult. MSC products appear safe in the short- and midterm, but studies with a long follow-up are scarce. Although the current number of randomized clinical studies is low, stem-cell products may have therapeutic potential. However, these regenerative technologies still need to be optimized.