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Cell Journal، جلد ۱۵، شماره Suppl ۱، صفحات ۶-۶
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عنوان انگلیسی Is-13: Migration and Differentiation Capacity of Mesenchymal Stem Cells from Patients with Osteoarthritis Towards In Situ Joint Cartilage Tissue
چکیده انگلیسی مقاله Objective: Today, for the regenerative treatment of injured or early osteoarthritic (OA) cartilage, autologous chondrocyte implantation (ACI) or matrix assisted ACI (MACI) are clinically applied. Also mesenchymal stem cell (MSC) approaches have reached the clinic, combining microfracture with the implantation of a collagen membrane (AMIC) or PGA/hyaluronan scaffold (Chondrotissue). AMIC is a passive approach; endogenous MSC flow into the membrane. Chondrotissue, in whose development we were involved, is between passive and active; MSC flow into the scaffold is enhanced by the addition of MSC recruiting serum. Our aim is to develop an active in situ approach, wherein the implantation of scaffolds loaded with MSC recruiting chemokines (CK) and differentiation factors, combined with microfracture, allows the use of endogenous MSC for cartilage regeneration. In this lecture, we will present the international state of the art and our own results. Materials and Methods: Bone marrow MSC of normal donors (ND) and OA patients were characterized (growth kinetics, FACS CD marker profile, multilineage assays). Also their CK receptor profile (qPCR, antibodies), CK release profile (protein array) and CK dependent migration (chemotaxis assays) was elucidated. Moreover, expression profiles of CK stimulated ND and OA MSC were compared (microarrays). Selected CK were encapsulated in PLGA release particles, and in vitro and in vivo applied to attract superparamagnetic iron oxide nanoparticle (SPION) labeled MSC (rat model, MRI). Finally, comparative gene expression profiling was performed for ND and OA MSC fibrinogen/ PLGA implants after chondrogenic induction. Results: ND and OA MSC have a similar doubling time, differentiate to fat, bone and cartilage, are CD73, CD105 positive, and CD45 negative. Moreover, both express most CK receptors. Proteomics revealed similar CK release profiles. Based on 96-well chemotaxis assays, they also show a similar CK dependent migration potential. Promising CK like CCL25 (TECK) and CXCL12 (SDF1•) were analyzed in more detail. CCL25 recruited a high number of ND and OA MSC and represents a promising new candidate for in situ approaches. Expression profiling of CCL25 and CXCL12 induced ND and OA MSC gave us a deep insight into their mobilization. For example, 22 genes were differentially expressed in both ND and OA MSC. Most are involved in homing (PDE4B), movement (PTGS2) and cytoskeletal and membrane reorganization (IGFBP1). In an ongoing study, CCL25 loaded PLGA particles are tested in a rat model. Here, for in vivo MRI monitoring of MSC migration towards CK releasing particles, SPION labeled MSC are used. Finally, the regenerative potential of OA and ND MSC was studied in fibrinogen/PLGA transplants. Here, chondrogenesis resulted in fibro- and joint cartilage, and ND and OA expression profiles showed a similar expression of marker genes known in context of OA (COL10A1, MMP1 and -3). Conclusion: We have shown that end-stage OA MSC behave like ND MSC, and that we have established the key knowledge and tools for an active, MSC based in situ therapy of injured or OA joint cartilage. This will be presented in this keynote in context of the international state of the art.
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نشانی اینترنتی http://celljournal.org/journal/article/abstract/778
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