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J Cell Mol Med. 2017 Nov;21(11):2748-2758. doi: 10.1111/jcmm.13190. Epub 2017 May 3.

Peripheral blood aspirates overexpressing IGF-I via rAAV gene transfer undergo enhanced chondrogenic differentiation processes.

Author information

1
Center of Experimental Orthopaedics, Saarland University Medical Center, Homburg/Saar, Germany.
2
Department of Orthopaedic Surgery, Saarland University Medical Center, Homburg/Saar, Germany.

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.

KEYWORDS:

IGF-I; cartilage repair; gene therapy; peripheral blood; rAAV vectors

PMID:
28467017
PMCID:
PMC5661259
DOI:
10.1111/jcmm.13190
[Indexed for MEDLINE]
Free PMC Article

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