Neutralisation of TGF beta or binding of VLA-4 to fibronectin prevents rat tendon adhesion following transection.
ABSTRACT Following tendon injury, severe loss of function often occurs either as a result of obliteration of the synovial canal with fibrous scar tissue or from rupture of the repaired tendon. The role of cell engineering in tendon repair is to promote strong and rapid healing of tendon whilst at the same time facilitating rapid reconstitution of the synovial canal. Modification of the immediate inflammatory response around healing tendon has been found to be of value. Experimentally this has been achieved by neutralisation of transforming growth factor-beta over the first 3 days following injury, or by blockade of inflammatory cell binding to the CS-1 locus on fibronectin with an anti-VLA-4 antibody, or with the synthetic VLA-4 inhibitor, CS-1 peptide, in a rat model of tendon transection. It is concluded from this pilot study that the treatments described hold promise in improving outcomes of the common clinical problem of tendon injury in man.
- SourceAvailable from: Alireza Moshaverinia[Show abstract] [Hide abstract]
ABSTRACT: Tendon injuries are often associated with significant dysfunction and disability due to tendinous tissue's very limited self-repair capacity and propensity for scar formation. Dental-derived mesenchymal stem cells (MSCs) in combination with appropriate scaffold material present an alternative therapeutic option for tendon repair/regeneration that may be advantageous compared to other current treatment modalities. The MSC delivery vehicle is the principal determinant for successful implementation of MSC-mediated regenerative therapies. In the current study, a co-delivery system based on TGF-β3-loaded RGD-coupled alginate microspheres was developed for encapsulating periodontal ligament stem cells (PDLSCs) or gingival mesenchymal stem cells (GMSCs). The capacity of encapsulated dental MSCs to differentiate into tendon tissue was investigated in vitro and in vivo. Encapsulated dental-derived MSCs were transplanted subcutaneously into immunocompromised mice. Our results revealed that after 4 weeks of differentiation in vitro, PDLSCs and GMSCs as well as the positive control human bone marrow mesenchymal stem cells (hBMMSCs) exhibited high levels of mRNA expression for gene markers related to tendon regeneration (Scx, DCn, Tnmd, and Bgy) via qPCR measurement. In a corresponding in vivo animal model, ectopic neo-tendon regeneration was observed in subcutaneous transplanted MSC-alginate constructs, as confirmed by histological and immunohistochemical staining for protein markers specific for tendons. Interestingly, in our quantitative PCR and in vivo histomorphometric analyses, PDLSCs showed significantly greater capacity for tendon regeneration than GMSCs or hBMMSCs (P < 0.05). Altogether, these findings indicate that periodontal ligament and gingival tissues can be considered as suitable stem cell sources for tendon engineering. PDLSCs and GMSCs encapsulated in TGF-β3-loaded RGD-modified alginate microspheres are promising candidates for tendon regeneration.Biomaterials 01/2014; · 8.31 Impact Factor
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ABSTRACT: Peritendinous fibrotic adhesions after tendon surgery are still a problem up-to-date. Approaches to overcome or at least minimize adhesion formation include implantation of barrier materials, application of lubricants or combinations of materials and functionalized drugs that are controllably released and support the healing tendon to glide and achieve the full range of motion after regeneration. Although a huge amount of different materials have been experimentally tested, the optimal strategy with respect to material and method has not yet been determined. In this review, we present a historical overview of physical barriers as well as liquid agents that have been used in order to prevent peritendinous adhesion formation. The materials are divided according to their first publication into two time frames; before and after 1980. There is no claim to include all materials tested neither will the “best” material be chosen; however, we present several materials that were experimentally tested in different animal trials as well as in clinical trials in contrast to other materials that were only tested once and disappeared from the assortment of anti-adhesives; which as such is a valuable information about its applicability for this purpose. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2014.Journal of Biomedical Materials Research Part B Applied Biomaterials 05/2014; · 2.31 Impact Factor
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ABSTRACT: Integrins are cell surface receptors that connect extracellular matrix (ECM) components to the actin cytoskeleton and transmit chemical and mechanical signals into the cells through adhesion complexes. Integrin-activated downstream pathways have been implicated in the regulation of various cellular functions, including proliferation, survival, migration, and differentiation. Integrin-based attachment to the matrix plays a central role in development, tissue morphogenesis, adult tissue homeostasis, remodeling and repair, and disturbance of the ECM-integrin-cytoskeleton signaling axis often results in diseases and tissue dysfunction. Increasing amount of in vitro and in vivo evidences suggest that integrins are pivotal for proper development, function, and regeneration of skeletal tissues. In this paper, we will summarize and discuss the role of integrins in skeletogenesis and their influence on the physiology and pathophysiology of cartilage, bone, and tendon. Birth Defects Research (Part C) 102:13-36, 2014. © 2014 Wiley Periodicals, Inc.Birth Defects Research Part C Embryo Today Reviews 03/2014; 102(1):13-36. · 4.44 Impact Factor