Effect of allogeneic cell-based tissue-engineered treatments in a sheep osteonecrosis model
CovenanteeUniversitat Autònoma de Barcelona; Vall d'Hebron Institut de Recerca; Hospital Universitari Vall d'Hebron; Universitat de Barcelona
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Osteonecrosis of the femoral head (ONFH) is defined as a tissue disorder and successive subchondral bone collapse resulting from an ischemic process, which may progress to hip osteoarthritis. Cell therapy with multipotent bone marrow mesenchymal stromal cells (BM-MSC) of autologous origin appears to be safe and has shown regenerative potential in previous preclinical and clinical studies. The use of allogeneic cells is far more challenging, but may be a promising alternative to use of autologous cells. Moreover, an optimized dosage of cells from an allogeneic source is needed to obtain off-the-shelf tissue engineering products (TEPs). The purpose of this study was to evaluate the efficacy of a TEP composed of undifferentiated ex vivo expanded BM-MSC of allogeneic origin, combined with bone matrix particles in variable doses. A comparative analysis of TEP's bone regenerative properties against its autologous counterpart was performed in an early-stage ONFH preclinical model in mature sheep. Allogeneic BM-MSC groups demonstrated bone regeneration capacity in osteonecrotic lesions equivalent to autologous BM-MSC groups 6 weeks after treatment. Likewise, stimulation of bone regeneration by a low cell dose of 0.5¿×¿106 BM-MSC/cm3 was equivalent to that of a high cell dose, 5¿×¿106 BM-MSC/cm3. Neither local nor systemic immunological reactions nor tumorigenesis were reported, strengthening the safety profile of allogeneic BM-MSC therapy in this model. Our results suggest that low-dose allogeneic BM-MSC is sufficient to promote bone regeneration in femoral head osteonecrotic lesions, and should be considered in translation of new allogeneic cell-based TEPs to human clinics.
CitationLópez, A. [et al.]. Effect of allogeneic cell-based tissue-engineered treatments in a sheep osteonecrosis model. "Tissue engineering. Part A, tissue engineering", 27 Març 2020, vol. 26, núm. 17-18, p. 1-12.
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