Priming with ligands secreted by human stromal progenitor cells promotes grafts of cardiac stem/progenitor cells after myocardial infarction.
Priming with ligands secreted by human stromal progenitor cells promotes grafts of cardiac stem/progenitor cells after myocardial infarction.
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DOI：
10.1002/stem.1546
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发表时间：
2014-03
期刊：
影响因子：
5.2
通讯作者：
Spees, Jeffrey L.
中科院分区：
文献类型：
--
作者：
Iso, Yoshitaka;Rao, Krithika S.;Poole, Charla N.;Zaman, A. K. M. Tarikuz;Curril, Ingrid;Sobel, Burton E.;Kajstura, Jan;Anversa, Piero;Spees, Jeffrey L.
培养扩增的成体干细胞/祖细胞的移植通常会导致细胞植入、存活和迁移到组织损伤部位的情况较差。包括成纤维细胞和基质细胞在内的间充质细胞分泌的因子可保护受损组织、促进组织修复并支持培养中多种类型的干/祖细胞。我们假设，来自成人骨髓源性多能基质细胞（MSC）的条件培养基（CdM）中的分泌因子可用于激发成人心脏干/祖细胞（CSC/CPC）并提高心肌梗死（MI）后的移植成功率。将成年大鼠 CPC 在通过塑料粘附或通过针对 CD271（又名 p75 低亲和力神经生长因子受体；p75MSC）的磁性分选分离的人 MSC 中分离的 CdM 中进行培养，诱导 CPC 中 STAT3 和 Akt 的磷酸化，支持其在常氧条件下的增殖和在缺氧条件（1% 氧气）下的存活。在 MI 后 1 天移植到心外膜下组织之前，用 30x p75MSC CdM 启动 CSC 30 分钟，与载体启动相比，显着增加了植入。使用中和/阻断抗体筛选 CdM，确定结缔组织生长因子 (CTGF) 和胰岛素是 p75MSC CdM 中保护 CPC 的关键因素。人 CTGF 肽 (CTGF-D4) 和胰岛素在培养物缺氧期间协同促进 CPC 存活。与 CdM 引发类似，移植前用 CTGF-D4 和胰岛素引发 CSC 30 分钟，可促进 MI 后 1 周和 1 个月时 CSC 衍生物的稳健植入、存活和迁移。我们的结果表明，用 CTGF-D4 和胰岛素短期启动人类 CSC 可以改善 MI 患者的移植成功率和心脏再生。
Transplantation of culture-expanded adult stem/progenitor cells often results in poor cellular engraftment, survival, and migration into sites of tissue injury. Mesenchymal cells including fibroblasts and stromal cells secrete factors that protect injured tissues, promote tissue repair, and support many types of stem/progenitor cells in culture. We hypothesized that secreted factors in conditioned medium (CdM) from adult bone marrow-derived multipotent stromal cells (MSCs) could be used to prime adult cardiac stem/progenitor cells (CSCs/CPCs) and improve graft success after myocardial infarction (MI). Incubation of adult rat CPCs in CdM from human MSCs isolated by plastic adherence or by magnetic sorting against CD271 (a.k.a., p75 low-affinity nerve growth factor receptor; p75MSCs) induced phosphorylation of STAT3 and Akt in CPCs, supporting their proliferation under normoxic conditions and survival under hypoxic conditions (1% oxygen). Priming CSCs with 30x p75MSC CdM for 30 min prior to transplantation into sub-epicardial tissue 1 day after MI markedly increased engraftment compared with vehicle priming. Screening CdM with neutralizing/blocking antibodies identified Connective Tissue Growth Factor (CTGF) and Insulin as key factors in p75MSC CdM that protected CPCs. Human CTGF peptide (CTGF-D4) and Insulin synergistically promoted CPC survival during hypoxia in culture. Similar to CdM priming, priming of CSCs with CTGF-D4 and Insulin for 30 min prior to transplantation promoted robust engraftment, survival and migration of CSC derivatives at 1 week and 1 month after MI. Our results indicate that short-term priming of human CSCs with CTGF-D4 and Insulin may improve graft success and cardiac regeneration in patients with MI.
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影响因子：
20.1
作者：
Hatzistergos KE;Quevedo H;Oskouei BN;Hu Q;Feigenbaum GS;Margitich IS;Mazhari R;Boyle AJ;Zambrano JP;Rodriguez JE;Dulce R;Pattany PM;Valdes D;Revilla C;Heldman AW;McNiece I;Hare JM
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5.2
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影响因子：
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