Influence of insulin-like growth factor I overexpression via recombinant adeno-associated vector gene transfer upon the biological activities and differentiation potential of human bone marrow-derived mesenchymal stem cells.
Influence of insulin-like growth factor I overexpression via recombinant adeno-associated vector gene transfer upon the biological activities and differentiation potential of human bone marrow-derived mesenchymal stem cells.
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DOI：
10.1186/scrt491
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发表时间：
2014-08-27
影响因子：
7.5
通讯作者：
Cucchiarini M
中科院分区：
文献类型：
--
作者：
Frisch J;Venkatesan JK;Rey-Rico A;Schmitt G;Madry H;Cucchiarini M
骨髓间充质干细胞（MSCs）等基因修饰的祖细胞的移植是一种有吸引力的策略，以提高关节软骨缺损的自然愈合。在本研究中，我们研究了通过基因转移持续过表达促有丝分裂和促合成代谢胰岛素样生长因子I（IGF-I）对人骨髓间充质干细胞（hMSCs）生物学活性的潜在益处。重组腺相关载体（rAAV）用于在未分化的和软骨诱导的原代hMSC中递送人IGF-I编码序列，以确定转基因表达的功效和持续时间，以及在体外21天后相对于对照（lacZ）处理，遗传修饰对细胞的软骨形成与成骨分化谱的后续影响。IGF-I的显著和延长的表达在未分化的hMSC中得到证实，并且最重要的是在用候选rAAV-hIGF-I载体转导长达21天的软骨形成诱导的hMSC中得到证实，导致与rAAV-lacZ处理相比增强的增殖、生物合成和软骨形成活性。在本文应用的条件下实现的IGF-I的过表达也增加了经处理的细胞中肥大和成骨标志物的表达。这些结果表明，rAAV表达的严格调节可能是必要的进一步翻译的方法在临床相关的动物模型在体内。然而，目前的研究结果支持使用这种类型的载体作为一种有效的工具，通过基因和干细胞为基础的程序来治疗关节软骨缺损的概念。
The transplantation of genetically modified progenitor cells such as bone marrow-derived mesenchymal stem cells (MSCs) is an attractive strategy to improve the natural healing of articular cartilage defects. In the present study, we examined the potential benefits of sustained overexpression of the mitogenic and pro-anabolic insulin-like growth factor I (IGF-I) via gene transfer upon the biological activities of human MSCs (hMSCs). Recombinant adeno-associated vectors (rAAV) were used to deliver a human IGF-I coding sequence in undifferentiated and chondrogenically-induced primary hMSCs in order to determine the efficacy and duration of transgene expression and the subsequent effects of the genetic modification upon the chondrogenic versus osteogenic differentiation profiles of the cells relative to control (lacZ) treatment after 21 days in vitro. Significant and prolonged expression of IGF-I was evidenced in undifferentiated and most importantly in chondrogenically-induced hMSCs transduced with the candidate rAAV-hIGF-I vector for up to 21 days, leading to enhanced proliferative, biosynthetic, and chondrogenic activities compared with rAAV-lacZ treatment. Overexpression of IGF-I as achieved in the conditions applied here also increased the expression of hypertrophic and osteogenic markers in the treated cells. These results suggest that a tight regulation of rAAV expression may be necessary for further translation of the approach in clinically relevant animal models in vivo. However, the current findings support the concept of using this type of vector as an effective tool to treat articular cartilage defects via gene- and stem cell-based procedures.
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DOI：
10.1302/0301-620x.85b2.13543
发表时间：
2003-03-01
影响因子：
--
作者：
Bentley, G;Biant, LC;Pringle, J
通讯作者：
Pringle, J
影响因子：
--
作者：
Ikeda, T;Kamekura, S;Chung, UI
通讯作者：
Chung, UI
影响因子：
--
作者：
Mendes, SC;Tibbe, JM;Van Blitterswijk, CA
通讯作者：
Van Blitterswijk, CA
影响因子：
2.6
作者：
Kawamura, K;Chu, CR;Niyibizi, C
通讯作者：
Niyibizi, C
DOI：
10.1111/j.1582-4934.2008.00474.x
发表时间：
2009-08-01
影响因子：
5.3
作者：
Cucchiarini, Magali;Terwilliger, Ernest F.;Madry, Henning
通讯作者：
Madry, Henning