Abstract
Implantation of peripheral blood aspirates induced towards chondrogenic differentiation upon genetic modification in sites of articular cartilage injury may represent a powerful strategy to enhance cartilage repair. Such a single‐step approach may be less invasive than procedures based on the use of isolated or concentrated MSCs, simplifying translational protocols in patients. In this study, we provide evidence showing the feasibility of overexpressing the mitogenic and pro‐anabolic insulin‐like growth factor I (IGF‐I) in human peripheral blood aspirates via rAAV‐mediated gene transfer, leading to enhanced proliferative and chondrogenic differentiation (proteoglycans, type‐II collagen, SOX9) activities in the samples relative to control (reporter rAAV‐lacZ) treatment over extended periods of time (at least 21 days, the longest time‐point evaluated). Interestingly, IGF‐I gene transfer also triggered hypertrophic, osteo‐ and adipogenic differentiation processes in the aspirates, suggesting that careful regulation of IGF‐I expression may be necessary to contain these events in vivo. Still, the current results demonstrate the potential of targeting human peripheral blood aspirates via therapeutic rAAV transduction as a novel, convenient tool to treat articular cartilage injuries.
Highlights
Damaged adult hyaline articular cartilage, the tissue that is essential for weight absorption and smooth gliding of the articulating surfaces in diarthroidal joints, does not naturally undergo competent repair processes in the absence of blood vessels and lymphatic drainage that may provide regenerative progenitor cells in sites of injury [1]
Human peripheral blood aspirates were transduced with rAAVhIGF-I to test the potential effects of insulin-like growth factor I (IGF-I) overexpression on the a 2017 The Authors
Direct modification of peripheral blood aspirates using the clinically relevant, highly effective recombinant AAV (rAAV) gene vectors is a promising strategy to enhance the chondrogenic differentiation of PB-MSCs for further convenient therapeutic application in articular cartilage lesions [1]
Summary
Damaged adult hyaline articular cartilage, the tissue that is essential for weight absorption and smooth gliding of the articulating surfaces in diarthroidal joints, does not naturally undergo competent repair processes in the absence of blood vessels and lymphatic drainage that may provide regenerative progenitor cells in sites of injury [1]. Lesions such as traumatic focal defects or occurring in osteoarthritis (OA) are infiltrated by cells migrating from the synovial membrane that fail to produce high-quality repair tissue, leading to progression of the injury over time [2]. Transplantation of bone marrow aspirates or concentrates has been attempted to further enhance the processes of cartilage repair [5,6,7,8,9,10] compared with the more a 2017 The Authors.
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