Human very Small Embryonic-like Cells Support Vascular Maturation and Therapeutic Revascularization Induced by Endothelial Progenitor Cells
Human very Small Embryonic-like Cells Support Vascular Maturation and Therapeutic Revascularization Induced by Endothelial Progenitor Cells
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DOI：
10.1007/s12015-017-9731-7
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发表时间：
2017-08-01
影响因子：
4.8
通讯作者：
Smadja, David M.
中科院分区：
文献类型：
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作者：
Guerin, Coralie L.;Rossi, Elisa;Smadja, David M.
非常小的胚胎样干细胞(VSEL)是主要的多能干细胞，定义为小细胞系阴性，CD133阳性，CD45阴性。我们之前描述了人骨髓VSEL能够分化为内皮细胞，并在手术诱导的严重肢体缺血小鼠中促进缺血后的血管重建。在目前的工作中，我们从严重肢体缺血患者中分离出骨髓VSEL，并研究其支持内皮祖细胞治疗能力和血管重建潜力的能力。在血管生成介质中培养的分选骨髓VSEL与内皮祖细胞共注射，已被证明在免疫缺陷小鼠中触发缺血后血管重建，并在Matrigel植入物中比人骨髓间充质干细胞更好地支持体内血管形成。总之，VSEL是一种潜在的治疗细胞的新来源，可能会在人类中产生血管内皮细胞和血管周围细胞。VSEL是目前描述的第一个能够在成人血管内皮细胞和血管周围细胞中分化的真正的血管生成干细胞。因此，由于VSEL存在于成人组织中，我们认为VSEL是一种CD45阴性的干细胞，能够在人体组织和血管中诱导血管再生。
Very small embryonic-like stem cells (VSELs) are major pluripotent stem cells defined as cells of small size being Lineage- negative, CD133-positive, and CD45-negative. We previously described that human bone marrow VSELs were able to differentiate into endothelial cells and promoted post-ischemic revascularization in mice with surgically induced critical limb ischemia. In the present work, we isolated bone marrow VSELs from patients with critical limb ischemia and studied their ability to support endothelial progenitor cells therapeutic capacity and revascularization potential. Sorted bone marrow VSELs cultured in angiogenic media were co-injected with endothelial progenitor cells and have been show to trigger post-ischemic revascularization in immunodeficient mice, and support vessel formation in vivo in Matrigel implants better than human bone marrow mesenchymal stem cells. In conclusion, VSELs are a potential new source of therapeutic cells that may give rise to cells of the endothelial and perivascular lineage in humans. VSELs are the first real vasculogenic stem cells able to differentiate in endothelial and perivascular lineage in human adult described from now. Thus, because VSELs presence have been proposed in adult tissues, we think that VSELs are CD45 negative stem cells able to give rise to vascular regeneration in human tissues and vessels.