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Immunomodulatory and osteogenic differentiation effects of mesenchymal stem cells by adenovirus‐mediated coexpression of CTLA4Ig and BMP2
Author(s) -
Zhang Xiaoling,
Zhang Chao,
Tang Tingting,
Qu Zhihu,
Lou Jueren,
Dai Kerong
Publication year - 2008
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.20489
Subject(s) - mesenchymal stem cell , bone morphogenetic protein 2 , genetic enhancement , biology , cancer research , microbiology and biotechnology , stem cell , immunology , cytotoxic t cell , in vitro , gene , genetics
Many reports have previously utilized a human bone morphogenetic protein 2 (BMP2)‐expressing recombinant adenoviral vector (AdBMP2) and mesenchymal stem cells (MSCs) for osteoinductive gene therapy. However, immunosuppression is essential for osteoinduction by AdBMP2, and this is one of the major impediments to its clinical use. In the present study, in vitro propagated MSCs were transduced using an adenoviral (Ad) vector to express the gene encoding cytotoxic T lymphocyte antigen 4‐immunoglobulin (CTLA4Ig). Lymphocyte response was induced by allogeneic‐irradiated MSCs as stimulators. We also examined the effects of cotransfection with a combination of the CTLA4Ig and the BMP2 gene on osteoblastic cell differentiation. The results showed that BMP2 gene transfected MSC elicited significant stimulatory responses, and one‐way MLR reactions were significantly blunted by CTLA4Ig. Further study demonstrates that cotransfection of MSCs with the combination of the CTLA4Ig and the BMP2 gene stimulates osteoblastic cell differentiation in vitro. The findings suggest that genetic engineering of MSCs to express an immunosuppressive molecule in combination with an osteogenic protein gene may have potential application in the treatment of several genetic diseases and in bone reconstruction. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:314–321, 2008