Stem cell recruitment factors secreted from cord blood-derived stem cells that are not secreted from mature endothelial cells enhance wound healing
Stem cell recruitment factors secreted from cord blood-derived stem cells that are not secreted from mature endothelial cells enhance wound healing
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DOI：
10.1007/s11626-013-9687-0
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发表时间：
2014-02-01
影响因子：
2.1
通讯作者：
Chae, Jung-Il
中科院分区：
文献类型：
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作者：
Kim, Jumi;Lee, Ji Hye;Chae, Jung-Il
伤口是最常见的医疗并发症之一。干细胞作为一种治疗创面的新方法最近受到重视，但也观察到了异基因干细胞移植的一些负面因素，如细胞来源的限制和体内未知的副作用。为了解决和消除这些副作用，我们在皮肤切除创面模型上检测了人脐血源干细胞(HCB-SCs)和人脐血管内皮细胞(HUVECs)释放的分泌因子对伤口的修复作用。HcB-SCs保留了内皮祖细胞的特性，并表达CD73、CD105和CD44等MSC标志。对HCB-SC条件培养液(CM)的分析表明，HCB-SC分泌独特的细胞因子和趋化因子，如转化生长因子β、PDGF、碱性成纤维细胞生长因子、表皮生长因子、KGF和血管内皮生长因子，这些细胞因子和趋化因子在正常的血管生成和伤口愈合中起重要作用。此外，HCB-SCs还能分泌G-CSF和GM-CSF等干细胞募集因子，而HUVECs则不能。在创面应用CB-SC-CM时，与HUVEC-CM组和对照组相比，HCB-SC-CM组创面愈合速度加快。此外，HCB-SC-CM治疗后创面肉芽组织和再上皮化速度加快，提示HCB-SC-CM的治疗作用源于干细胞分泌的干细胞募集因子，而不仅仅是内皮祖细胞。综上所述，这些结果表明，干细胞释放的分泌因子，而不仅仅是内皮细胞，可能是干细胞治疗缺血性组织疾病的重要媒介。
Wounds are one of the most frequently occurring medical complication. Stem cells were recently highlighted as a novel therapeutic approach to treating wounds, although some negative aspects of allogenic stem cell transplantation were observed, such as cellular source limitations and unknown side effects in vivo. To address and eliminate these side effects, we examined the wound healing effect of secretory factors released from human cord blood-derived stem cells (hCB-SCs) and human umbilical vascular endothelial cells (HUVECs) on cutaneous excisional wound models. The hCB-SCs retained endothelial progenitor cell characteristics and expressed MSC markers such as CD73, CD105, and CD44. Analysis of hCB-SC-conditioned medium (CM) indicated that hCB-SCs secrete distinctly unique cytokines and chemokines such as TGF-beta, PDGF, bFGF, EGF, KGF, and VEGF, which are well known to be important in normal angiogenesis and wound healing. Furthermore, hCB-SCs also secreted stem cell-recruiting factors such as G-CSF and GM-CSF, whereas HUVECs did not. When CB-SC-CM was applied to wound sites, hCB-SC-CM accelerated the wound healing rate compared with HUVEC-CM- and control medium-treated groups. In addition, hCB-SC-CM treatment caused a more rapid re-formation of granulation tissue and re-epithelialization of wounds, which indicates that the therapeutic effect of hCB-SC-CM is due to secreted stem cell-recruiting factors from stem cells, not just from endothelial lineage cells. Taken together, these results suggest that secretory factors released from stem cells, not just from endothelial cells, could be an important mediator of stem cell therapy in ischemic tissue diseases.