Microparticles from kidney-derived mesenchymal stem cells act as carriers of proangiogenic signals and contribute to recovery from acute kidney injury.
Microparticles from kidney-derived mesenchymal stem cells act as carriers of proangiogenic signals and contribute to recovery from acute kidney injury.
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DOI：
10.1371/journal.pone.0087853
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Park HC
中科院分区：
文献类型：
--
作者：
Choi HY;Moon SJ;Ratliff BB;Ahn SH;Jung A;Lee M;Lee S;Lim BJ;Kim BS;Plotkin MD;Ha SK;Park HC
我们最近证明了体外扩增的肾间充质干细胞（KMSC）在急性肾缺血再灌注损伤中保护肾小管周围毛细血管内皮细胞的作用。在此，我们从KMSC中分离和表征微粒（MP）。我们研究了它们对人内皮细胞的体外生物学作用和在急性缺血再灌注肾损伤中的体内肾保护作用。从在缺氧条件下在无血清培养基中培养24小时的KMSC的上清液中分离MP。KMSC衍生的MP证明存在通常在KMSC膜上表达的几种粘附分子，如CD 29、CD 44、CD 73、α4、5和6整合素。定量真实的时间PCR证实在分离的MP中存在VEGF-A（120，164，188）、bFGF和IGF-1的3种剪接变体。用PKH 26红色荧光染料标记的MP通过表面分子如CD 44、CD 29和α4、5和6整合素被培养的人脐静脉内皮细胞（HUVEC）掺入。MP剂量依赖性地改善体外HUVEC增殖，并促进生长因子减少的Matrigel上的内皮管形成。MPs还能抑制人微血管内皮细胞的凋亡。将KMSC衍生的MP给予急性肾缺血的小鼠，然后在缺血的肾脏中选择性植入并显着改善肾功能。这是通过促进肾小管周围毛细血管内皮细胞的增殖和改善肾小管周围微血管稀疏来实现的。我们的研究结果支持这一假设，即KMSC衍生的MP可能作为促血管生成信号的来源，并赋予缺血肾脏的肾保护作用。
We recently demonstrated the use of in vitro expanded kidney-derived mesenchymal stem cells (KMSC) protected peritubular capillary endothelial cells in acute renal ischemia-reperfusion injury. Herein, we isolated and characterized microparticles (MPs) from KMSC. We investigated their in vitro biologic effects on human endothelial cells and in vivo renoprotective effects in acute ischemia-reperfusion renal injury. MPs were isolated from the supernatants of KMSC cultured in anoxic conditions in serum-deprived media for 24 hours. KMSC-derived MPs demonstrated the presence of several adhesion molecules normally expressed on KMSC membranes, such as CD29, CD44, CD73, α4, 5, and 6 integrins. Quantitative real time PCR confirmed the presence of 3 splicing variants of VEGF-A (120, 164, 188), bFGF and IGF-1 in isolated MPs. MPs labeled with PKH26 red fluorescence dye were incorporated by cultured human umbilical vein endothelial cells (HUVEC) via surface molecules such as CD44, CD29, and α4, 5, and 6 integrins. MP dose dependently improved in vitro HUVEC proliferation and promoted endothelial tube formation on growth factor reduced Matrigel. Moreover, apoptosis of human microvascular endothelial cell was inhibited by MPs. Administration of KMSC-derived MPs into mice with acute renal ischemia was followed by selective engraftment in ischemic kidneys and significant improvement in renal function. This was achieved by improving proliferation, of peritubular capillary endothelial cell and amelioration of peritubular microvascular rarefaction. Our results support the hypothesis that KMSC-derived MPs may act as a source of proangiogenic signals and confer renoprotective effects in ischemic kidneys.
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影响因子：
19.6
作者：
Chen, Jun;Park, Hyeong-Cheon;Addabbo, Francesco;Ni, Jie;Pelger, Edward;Li, Houwei;Plotkin, Matthew;Goligorsky, Michael S.
通讯作者：
Goligorsky, Michael S.
影响因子：
3.7
作者：
Bruno S;Grange C;Collino F;Deregibus MC;Cantaluppi V;Biancone L;Tetta C;Camussi G
通讯作者：
Camussi G
影响因子：
20.3
作者：
Deregibus, Maria Chiara;Cantaluppi, Vincenzo;Camussi, Giovanni
通讯作者：
Camussi, Giovanni
影响因子：
6.1
作者：
Gatti, Stefano;Bruno, Stefania;Camussi, Giovanni
通讯作者：
Camussi, Giovanni
DOI：
10.1196/annals.1354.062
发表时间：
2006-01-01
期刊：
UNDERSTANDING AND MODULATING AGING
影响因子：
--
作者：
Kassem, Moustapha
通讯作者：
Kassem, Moustapha