包围一个红细胞(E)的内皮细胞外表面典型地排列着周细胞,图片来自维基共享资源。
来自以色列理工学院拉巴波特医学院和瑞本医学中心(Technion-Israel Institute of Technology's Rappaport Faculty of Medicine and Rambam Medical Center)的研究人员利用胚胎干细胞和经过重编程的成体干细胞第一次产生称作周细胞(pericyte)的细胞,而且产生的周细胞能够发生增殖,并且在健康血管形成中发挥着关键性作用。这项研究突破可能最终有益于从心血管疾病或者因为诸如糖尿病之类的疾病导致的严重性循环系统损伤中竭力康复过来的病人。
以色列理工学院柏林家庭干细胞研究实验室(Berlin Family Laboratory for Stem Cell Research)主任Joseph Itskovitz-Eldor教授与Ayelet Dar-Oaknin博士领导的一个研究小组然后将这些周细胞注射进小鼠受损的并且血液流动几乎完全被阻断的腿部肌肉。
只需3周时间,这些周细胞重建功能性的血管系统而且甚至能够再生因为缺乏氧气供给而受损的肌肉。这些结果为治疗遭受心脏或血管疾病和一系列其他疾病折磨的病人身上发生的组织损伤提供极大的希望。
瑞本医学中心主任和拉巴波特医学院前主管Rafael Beyar说,这些研究发现存在着“巨大的医疗潜力”,“但是应用于病人身上的道路仍然漫长”,不过人们可能也“不用等待太长的时间”。
作为研究焦点的周细胞是利用胚胎干细胞(来自捐献的受精卵)生产的,而且也可利用经过基因重编程变得“多能性”的成体干细胞来进行生产。因为周细胞是利用病人自己的干细胞构建出来的,所以它们能够被移植并且治愈受损组织,同时不会产生排斥风险。
Itskovitz-Eldor 教授是瑞本医学中心妇产科主任和以色列理工学院干细胞实验室与福尔曼家庭卓越中心主任(Forman Families Center for Excellence),研究领域是干细胞和组织再生。
相关研究发现近期发表在美国心脏协会期刊Circulation上。(生物谷:towersimper编译)
doi:10.1161/CIRCULATIONAHA.111.048264
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Multipotent Vasculogenic Pericytes From Human Pluripotent Stem Cells Promote Recovery of Murine Ischemic Limb
Ayelet Dar, PhD; Hagit Domev, MSc; Oren Ben-Yosef, BSc; Maty Tzukerman, PhD; Naama Zeevi-Levin, PhD; Atara Novak, MSc; Igal Germanguz, MSc; Michal Amit, PhD; Joseph Itskovitz-Eldor, MD, DSc
Background—Pericytes represent a unique subtype of microvessel-residing perivascular cells with diverse angiogenic functions and multilineage developmental features of mesenchymal stem cells. Although various protocols for derivation of endothelial and/or smooth muscle cells from human pluripotent stem cells (hPSC, either embryonic or induced) have been described, the emergence of pericytes in the course of hPSC maturation has not yet been elucidated.
Methods and Results—We found that during hPSC development, spontaneously differentiating embryoid bodies give rise to CD105+CD90+CD73+CD31− multipotent clonogenic mesodermal precursors, which can be isolated and efficiently expanded. Isolated and propagated cells expressed characteristic pericytic markers, including CD146, NG2, and platelet-derived growth factor receptor β, but not the smooth muscle cell marker α-smooth muscle actin. Coimplantation of hPSC-derived endothelial cells with pericytes resulted in functional and rapid anastomosis to the murine vasculature. Administration of pericytes into immunodeficient mice with limb ischemia promoted significant vascular and muscle regeneration. At day 21 after transplantation, recruited hPSC pericytes were found incorporated into recovered muscle and vasculature.
Conclusions—Derivation of vasculogenic and multipotent pericytes from hPSC can be used for the development of vasculogenic models using multiple vasculogenic cell types for basic research and drug screening and can contribute to angiogenic regenerative medicine.