Paracrine factors of mesenchymal stem cells recruit macrophages and endothelial lineage cells and enhance wound healing.
Paracrine factors of mesenchymal stem cells recruit macrophages and endothelial lineage cells and enhance wound healing.
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间充质干细胞的旁分泌因子招募巨噬细胞和内皮谱系细胞并增强伤口愈合
DOI：
10.1371/journal.pone.0001886
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发表时间：
2008-04-02
期刊：
影响因子：
3.7
通讯作者：
Wu Y
中科院分区：
文献类型：
--
作者：
Chen L;Tredget EE;Wu PY;Wu Y
骨髓间充质干细胞（BM-MSCs）已被证明可以促进伤口愈合;然而，所涉及的机制几乎不清楚。在这项研究中，我们研究了BM-MSCs释放的旁分泌因子及其对参与伤口愈合的细胞的影响，并与真皮成纤维细胞释放的因子进行了比较。通过Real-Time PCR和基于抗体的蛋白质阵列和ELISA对BM-MSC条件培养基的分析表明，BM-MSC分泌明显不同的细胞因子和趋化因子，例如与真皮成纤维细胞相比，更大量的VEGF-α、IGF-1、EGF、角质形成细胞生长因子、血管生成素-1、基质衍生因子-1、巨噬细胞炎性蛋白-1 α和β以及促红细胞生成素。已知这些分子在正常伤口愈合中是重要的。与成纤维细胞条件培养基相比，BM-MSC条件培养基显著增强巨噬细胞、角质形成细胞和内皮细胞的迁移以及角质形成细胞和内皮细胞的增殖。此外，在切除伤口愈合的小鼠模型中，其中应用浓缩的BM-MSC条件培养基，与施用预条件培养基或成纤维细胞条件培养基相比，发生加速的伤口愈合。通过流式细胞术对来自伤口的细胞悬液的分析表明，与用预条件培养基或成纤维细胞条件培养基处理的伤口相比，用BM-MSC条件培养基处理的伤口具有增加的CD 4/80阳性巨噬细胞和Flk-1-、CD 34-或c-kit阳性内皮（祖）细胞的比例。与上述发现一致，伤口切片的免疫组织化学分析显示，用BM-MSC条件培养基处理的伤口具有增加的巨噬细胞丰度。我们的研究结果表明，BM-MSCs释放的因子招募巨噬细胞和内皮细胞进入伤口，从而促进伤口愈合。
Bone marrow derived mesenchymal stem cells (BM-MSCs) have been shown to enhance wound healing; however, the mechanisms involved are barely understood. In this study, we examined paracrine factors released by BM-MSCs and their effects on the cells participating in wound healing compared to those released by dermal fibroblasts. Analyses of BM-MSCs with Real-Time PCR and of BM-MSC-conditioned medium by antibody-based protein array and ELISA indicated that BM-MSCs secreted distinctively different cytokines and chemokines, such as greater amounts of VEGF-α, IGF-1, EGF, keratinocyte growth factor, angiopoietin-1, stromal derived factor-1, macrophage inflammatory protein-1alpha and beta and erythropoietin, compared to dermal fibroblasts. These molecules are known to be important in normal wound healing. BM-MSC-conditioned medium significantly enhanced migration of macrophages, keratinocytes and endothelial cells and proliferation of keratinocytes and endothelial cells compared to fibroblast-conditioned medium. Moreover, in a mouse model of excisional wound healing, where concentrated BM-MSC-conditioned medium was applied, accelerated wound healing occurred compared to administration of pre-conditioned or fibroblast-conditioned medium. Analysis of cell suspensions derived from the wound by FACS showed that wounds treated with BM-MSC-conditioned medium had increased proportions of CD4/80-postive macrophages and Flk-1-, CD34- or c-kit-positive endothelial (progenitor) cells compared to wounds treated with pre-conditioned medium or fibroblast-conditioned medium. Consistent with the above findings, immunohistochemical analysis of wound sections showed that wounds treated with BM-MSC-conditioned medium had increased abundance of macrophages. Our results suggest that factors released by BM-MSCs recruit macrophages and endothelial lineage cells into the wound thus enhancing wound healing.
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DOI：
10.1083/jcb.153.3.465
发表时间：
2001-04-30
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hintermann E;Bilban M;Sharabi A;Quaranta V
通讯作者：
Quaranta V
DOI：
10.1073/pnas.86.6.2018
发表时间：
1989-03-01
影响因子：
11.1
作者：
DANON, D;KOWATCH, MA;ROTH, GS
通讯作者：
ROTH, GS
影响因子：
2.9
作者：
Lamme, EN;Van Leeuwen, RTJ;Middelkoop, E
通讯作者：
Middelkoop, E
影响因子：
6.5
作者：
Ghahary, A;Marcoux, Y;Weinfeld, M
通讯作者：
Weinfeld, M
DOI：
10.1073/pnas.86.7.2229
发表时间：
1989-04-01
影响因子：
11.1
作者：
PIERCE, GF;MUSTOE, TA;DEUEL, TF
通讯作者：
DEUEL, TF