Torn Ligaments and Sports Injuries Stem Cell Treatments


Stem Cells For Torn LigamentsStem Cells for Torn Ligaments and Sports Injuries


Stem cells for tendon tissue engineering and regeneration.

Expert Opin Biol Ther. 2010 May;10(5):689-700

Authors: Yin Z, Chen X, Chen JL, Ouyang HW

Tendon injuries are common especially in sports activities, but tendon is a unique connective tissue with poor self-repair capability. With advances in stem cell biology, tissue engineering is becoming increasingly powerful for tissue regeneration.

Stem cells with capacity of multipotency and self-renewal are an ideal cell source for tissue engineering.

PMID: 20367125 [PubMed - indexed for MEDLINE]


Repair of chronic osteochondral defects using predifferentiated mesenchymal stem cells in an ovine model.

Am J Sports Med. 2010 Sep;38(9):1857-69

Authors: Zscharnack M, Hepp P, Richter R, Aigner T, Schulz R, Somerson J, Josten C, Bader A, Marquass B

The use of mesenchymal stem cells (MSCs) to treat osteochondral defects caused by sports injuries or disease is of particular interest. However, there is a lack of studies in large-animal models examining the benefits of chondrogenic predifferentiation in vitro for repair of chronic osteochondral defects.

Stem Cell Therapy for Sports Injuries

                           Sports Injuries and Stem Cell Therapy


Innovative strategies for treatment

of soft tissue injuries in human and animal athletes.

Med Sport Sci. 2009;54:150-65

Authors: Hoffmann A, Gross G

Our aim is to review the recent progress in the management of musculoskeletal disorders. We will cover novel therapeutic approaches based on growth factors, gene therapy and cells, including stem cells, which may be combined with each other as appropriate.

We focus mainly on the treatment of soft tissue injuries - muscle, cartilage, and tendon/ligament for both human and animal athletes.

The need for innovative strategies results from the fact that despite all efforts, the current strategies for cartilage and tendon/ligament still result in the formation of functionally and biomechanically inferior tissues after injury (a phenomenon called 'repair' as opposed to proper 'regeneration'), whereas the outcome for muscle is more favorable.

Innovative approaches are urgently needed not only to enhance the outcome of conservative or surgical procedures but also to speed up the healing process from the very long disabling periods, which is of special relevance for athletes.


The roles of TGF-beta1 gene transfer on collagen formation during Achilles tendon healing.

Biochem Biophys Res Commun. 2009 May 29;383(2):235-9

Authors: Hou Y, Mao Z, Wei X, Lin L, Chen L, Wang H, Fu X, Zhang J, Yu C

Collagen content and cross-linking are believed to be major determinants of tendon structural integrity and function. The current study aimed to investigate the effects of transforming growth factor (TGF)-beta1 on the collagen content and cross-linking of Achilles tendons, and on the histological and biomechanical changes occurring during Achilles tendon healing in rabbits.

Bone marrow-derived mesenchymal stem cells (BMSCs) transfected with the TGF-beta1 gene were surgically implanted into experimentally injured Achilles tendons. Collagen proteins were identified by immunohistochemical staining and fiber bundle accumulation was revealed by Sirius red staining.

Achilles tendons treated with TGF-beta1-transfected BMSCs showed higher concentrations of collagen I protein, more rapid matrix remodeling, and larger fiber bundles.

Thus TGF-beta1 can promote mechanical strength in healing Achilles tendons by regulating collagen synthesis, cross-link formation, and matrix remodeling.


Mesenchymal stem cell-based therapy for cartilage repair: a review.

Knee Surg Sports Traumatol Arthrosc. 2009 Nov;17(11):1289-97

Authors: Koga H, Engebretsen L, Brinchmann JE, Muneta T, Sekiya I

Articular cartilage injury remains one of the major concerns in orthopaedic surgery. Mesenchymal stem cell (MSC) transplantation has been introduced to avoid some of the side effects and complications of current techniques. The purpose of this paper is to review the literature on MSC-based cell therapy for articular cartilage repair to determine if it can be an alternative treatment for cartilage injury.

MSCs retain both high proliferative potential and multipotentiality, including chondrogenic differentiation potential, and a number of successful results in transplantation of MSCs into cartilage defects have been reported in animal studies. However, the use of MSCs for cartilage repair is still at the stage of preclinical and phase I studies, and no comparative clinical studies have been reported. Therefore, it is difficult to make conclusions in human studies.

This requires randomized clinical trials to evaluate the effectiveness of cell-based cell therapy for cartilage repair.

Related Articles Human Subacromial Bursal Cells Display Superior Engraftment Versus Bone Marrow Stromal Cells in Murine Tendon Repair. Am J Sports Med. 2018 12;46(14):3511-3520 Authors: Dyrna F, Zakko P, Pauzenberger L, McCarthy MB, Mazzocca AD, Dyment NA Abstract BACKGROUND: Bone marrow aspirate is a primary source for cell-based therapies with increasing value in the world of orthopaedic surgery, especially in revision cases of tendon and ligament repairs. However, cells within peritendinous structures, such as the paratenon and surrounding bursa, contribute to the native tendon-healing response and offer promising cell populations for cell-based repair strategies. Therefore, the purpose of this study is to investigate the efficacy of cells derived from human subacromial bursa as compared with the current gold standard, bone marrow stromal cells (BMSCs), for tendon repairs in an established in vivo immunodeficient murine patellar tendon defect model. HYPOTHESIS: Subacromial bursal cells will show superior survival and engraftment into the host tissue as compared with BMSCs. STUDY DESIGN: Controlled laboratory study. METHODS: Human subacromial bursal and bone marrow aspirate were harvested from the same donor undergoing rotator cuff repair. Cells were transfected with a fluorescent lentiviral vector to permanently label the cells, encapsulated into fibrin gel, and implanted into bilateral full-length central-width patellar tendon defects of immunodeficient mice. Additional surgery was performed on control mice comparing fibrin without cells and natural healing. At the time of sacrifice, all limbs were scanned on a multiphoton microscope to monitor the engraftment of the human donor cells. Afterward, limbs were assigned to either immunohistochemical or biomechanical analysis. RESULTS: As compared with BMSCs, implanted subacromial bursal cells displayed superior tissue engraftment and survival. The main healing response in this defect model was the creation of new healing tissue over the anterior surface of the defect space. The implantation of cells significantly increased the thickness of the anterior healing tissue as compared with control limbs that did not receive cells. Cell proliferation was also increased in limbs that received implanted cells, suggesting that the donor cells stimulated a more robust healing response. Finally, these changes in the healing response did not lead to significant changes in mechanical properties. CONCLUSION: The subacromial bursa, while often removed during rotator cuff repair, may harbor a more suitable cell source for tendon repair than BMSCs, as bursal cells display superior engraftment and survival in tendon tissue. In addition, the subacromial bursa may be a more accessible cell source than bone marrow aspirate. CLINICAL RELEVANCE: The subacromial bursa contains a cell population that responds to tendon injury and may provide a more optimal cell source for tendon repair and regeneration strategies. Therefore, cells could be harvested from this tissue in the future, as opposed to the current practice of bursectomy and debridement. PMID: 30419176 [PubMed - indexed for MEDLINE]
Related Articles Bone Marrow-Harvesting Technique Influences Functional Heterogeneity of Mesenchymal Stem/Stromal Cells and Cartilage Regeneration. Am J Sports Med. 2018 12;46(14):3521-3531 Authors: Sivasubramaniyan K, Ilas DC, Harichandan A, Bos PK, Santos DL, de Zwart P, Koevoet WJLM, Owston H, Bühring HJ, Jones E, van Osch GJVM Abstract BACKGROUND: Connective tissue progenitors (CTPs) from native bone marrow (BM) or their culture-expanded progeny, often referred to as mesenchymal stem/stromal cells, represents a promising strategy for treatment of cartilage injuries. But the cartilage regeneration capacity of these cells remains unpredictable because of cell heterogeneity. HYPOTHESIS: The harvest technique of BM may highly influence stem cell heterogeneity and, thus, cartilage formation because these cells have distinct spatial localization within BM from the same bone. STUDY DESIGN: Controlled laboratory study. METHODS: CTPs obtained from the femur of patients undergoing total hip replacement by 2 harvest techniques-BM aspiration and BM collection-after bone rasping were immunophenotyped by flow cytometry and evaluated for chondrogenic ability. The spatial localization of different CTP subsets in BM was verified by immunohistochemistry. RESULTS: Cells from the BM after rasping were significantly more chondrogenic than the donor-matched aspirate, whereas no notable difference in their osteogenic or adipogenic potential was observed. The authors then assessed whether distinct immunophenotypically defined CTP subsets were responsible for the different chondrogenic capacity. Cells directly isolated from BM after rasping contained a higher percentage (mean, 7.2-fold) of CD45-CD271+CD56+ CTPs as compared with BM aspirates. The presence of this subset in the harvested BM strongly correlated with chondrogenic ability, showing that CD271+CD56+ cells are enriched in chondroprogenitors. Furthermore, evaluation of these CTP subsets in BM revealed that CD271+CD56+ cells were localized in the bone-lining regions whereas CD271+CD56- cells were found in the perivascular regions. Since the iliac crest remains a frequent site of BM harvest for musculoskeletal regeneration, the authors also compared the spatial distribution of these subsets in trabeculae of femoral head and iliac crest and found CD271+CD56+ bone-lining cells in both tissues. CONCLUSION: Chondrogenically distinct CTP subsets have distinct spatial localization in BM; hence, the harvest technique of BM determines the efficiency of cartilage formation. CLINICAL RELEVANCE: The harvest technique of BM may be of major importance in determining the clinical success of BM mesenchymal stem/stromal cells in cartilage repair. PMID: 30419181 [PubMed - indexed for MEDLINE]

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