Paracrine proangiopoietic effects of human umbilical cord blood-derived purified CD133+ cells--implications for stem cell therapies in regenerative medicine.
Paracrine proangiopoietic effects of human umbilical cord blood-derived purified CD133+ cells--implications for stem cell therapies in regenerative medicine.
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DOI：
10.1089/scd.2012.0268
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发表时间：
2013-02
影响因子：
4
通讯作者：
J. Ratajczak;M. Kucia;Kasia Mierzejewska;W. Marlicz;Z. Pietrzkowski;W. Wojakowski;N. Greco;M. Tendera;M. Ratajczak
中科院分区：
文献类型：
--
作者：
J. Ratajczak;M. Kucia;Kasia Mierzejewska;W. Marlicz;Z. Pietrzkowski;W. Wojakowski;N. Greco;M. Tendera;M. Ratajczak
从造血组织纯化的CD 133+细胞主要富集造血干/祖细胞，但也含有一些内皮祖细胞和非常小的胚胎样干细胞。CD 133+细胞类似于CD 34+细胞，是再生医学中干细胞的潜在来源。然而，在用这些细胞治疗的患者的受损器官中缺乏令人信服的供体来源的嵌合体，这表明功能的改善涉及除了对受损组织的直接贡献之外的机制。我们假设CD 133+细胞分泌几种旁分泌因子，这些因子在治疗后观察到的积极作用中起主要作用，并检测了这些细胞的上清液中是否存在这些因子。我们观察到，CD 133+细胞和CD 133+细胞衍生的微泡（MV）表达几种抗凋亡和促血管生成因子的mRNA，包括kit配体、胰岛素生长因子-1、血管内皮生长因子、碱性成纤维细胞生长因子和白细胞介素-8。这些因子也在CD 133+细胞衍生的条件培养基（CM）中检测到。更重要的是，CD 133+细胞衍生的CM和MV化学吸引内皮细胞，并在体外和体内试验中显示促血管生成活性。在评估再生医学中纯化CD 133+细胞疗法的临床结果时，应考虑这一观察结果。
CD133+ cells purified from hematopoietic tissues are enriched mostly for hematopoietic stem/progenitor cells, but also contain some endothelial progenitor cells and very small embryonic-like stem cells. CD133+ cells, which are akin to CD34+ cells, are a potential source of stem cells in regenerative medicine. However, the lack of convincing donor-derived chimerism in the damaged organs of patients treated with these cells suggests that the improvement in function involves mechanisms other than a direct contribution to the damaged tissues. We hypothesized that CD133+ cells secrete several paracrine factors that play a major role in the positive effects observed after treatment and tested supernatants derived from these cells for the presence of such factors. We observed that CD133+ cells and CD133+ cell-derived microvesicles (MVs) express mRNAs for several antiapoptotic and proangiopoietic factors, including kit ligand, insulin growth factor-1, vascular endothelial growth factor, basic fibroblast growth factor, and interleukin-8. These factors were also detected in a CD133+ cell-derived conditioned medium (CM). More important, the CD133+ cell-derived CM and MVs chemoattracted endothelial cells and display proangiopoietic activity both in vitro and in vivo assays. This observation should be taken into consideration when evaluating clinical outcomes from purified CD133+ cell therapies in regenerative medicine.