Thrombospondin-1 promotes mesenchymal stromal cell functions via TGFβ and in cooperation with PDGF
Thrombospondin-1 promotes mesenchymal stromal cell functions via TGFβ and in cooperation with PDGF
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DOI：
10.1016/j.matbio.2016.03.003
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发表时间：
2016-09-01
期刊：
影响因子：
6.9
通讯作者：
Taraboletti, Giulia
中科院分区：
文献类型：
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作者：
Belotti, Dorina;Capelli, Chiara;Taraboletti, Giulia
间充质基质细胞（MSC）具有独特的创伤组织向性、高分化能力、诱导组织修复的能力以及抗炎和免疫调节活性。这引起了人们对它们在严重人类条件下的治疗用途以及再生医学和组织工程的兴趣。鉴定参与调节MSC增殖、迁移和分化的因子可以为MSC的病理生理调节提供见解，并可用于优化治疗用途的临床级扩增方案。TSP-1诱导MSC增殖。这种作用是由TSP-1诱导的内源性TGF β活化介导的，如抗TGF β抗体的抑制作用和不活化TGF β的TSP-2活性的缺乏所示。此外，TSP-1强烈增强PDGF在MSC上的增殖和迁移活性。TSP-1通过位于TSP-1 III型重复序列内的位点直接结合PDGF，并保护生长因子免受MSC衍生蛋白酶的降解，从而增加其稳定性和生物利用度。为进一步研究PDGF和TSP-1在MSC体外扩增中用于治疗应用的可能用途奠定了基础。(C)© 2016 Elsevier B. V.版权所有。
Mesenchymal stromal cells (MSC) are characterized by unique tropism for wounded tissues, high differentiating capacity, ability to induce tissue repair, and anti-inflammatory and immunoregulatory activities. This has generated interest in their therapeutic use in severe human conditions as well as in regenerative medicine and tissue engineering. Identification of factors involved in the regulation of MSC proliferation, migration and differentiation could provide insights into the pathophysiological regulation of MSC and be exploited to optimize clinical grade expansion protocols for therapeutic use.Here we identify thrombospondin-1 (TSP-1) as a major regulator of MSC. TSP-1 induced MSC proliferation. This effect was mediated by TSP-1-induced activation of endogenous TGF beta, as shown by the inhibitory effects of anti-TGF beta antibodies and by the lack of activity of TSP-2-that does not activate TGF beta. Moreover, TSP-1 strongly potentiated the proliferative and migratory activity of PDGF on MSC. TSP-1 directly bound to PDGF, through a site located within the TSP-1 type III repeats, and protected the growth factor from degradation by MSC-derived proteases, hence increasing its stability and bioavailability.The studies presented here identify a more comprehensive picture of the pleiotropic effect of TSP-1 on MSC behavior, setting the basis for further studies aimed at investigating the possible use of PDGF and TSP-1 in the in vitro expansion of MSC for therapeutic applications. (C) 2016 Elsevier B.V. All rights reserved.