包圍一個紅細胞(E)的內(nèi)皮細胞外表面典型地排列著周細胞,,圖片來自維基共享資源。
來自以色列理工學院拉巴波特醫(yī)學院和瑞本醫(yī)學中心(Technion-Israel Institute of Technology's Rappaport Faculty of Medicine and Rambam Medical Center)的研究人員利用胚胎干細胞和經(jīng)過重編程的成體干細胞第一次產(chǎn)生稱作周細胞(pericyte)的細胞,,而且產(chǎn)生的周細胞能夠發(fā)生增殖,,并且在健康血管形成中發(fā)揮著關(guān)鍵性作用。這項研究突破可能最終有益于從心血管疾病或者因為諸如糖尿病之類的疾病導(dǎo)致的嚴重性循環(huán)系統(tǒng)損傷中竭力康復(fù)過來的病人,。
以色列理工學院柏林家庭干細胞研究實驗室(Berlin Family Laboratory for Stem Cell Research)主任Joseph Itskovitz-Eldor教授與Ayelet Dar-Oaknin博士領(lǐng)導(dǎo)的一個研究小組然后將這些周細胞注射進小鼠受損的并且血液流動幾乎完全被阻斷的腿部肌肉,。
只需3周時間,這些周細胞重建功能性的血管系統(tǒng)而且甚至能夠再生因為缺乏氧氣供給而受損的肌肉,。這些結(jié)果為治療遭受心臟或血管疾病和一系列其他疾病折磨的病人身上發(fā)生的組織損傷提供極大的希望,。
瑞本醫(yī)學中心主任和拉巴波特醫(yī)學院前主管Rafael Beyar說,這些研究發(fā)現(xiàn)存在著“巨大的醫(yī)療潛力”,,“但是應(yīng)用于病人身上的道路仍然漫長”,,不過人們可能也“不用等待太長的時間”。
作為研究焦點的周細胞是利用胚胎干細胞(來自捐獻的受精卵)生產(chǎn)的,,而且也可利用經(jīng)過基因重編程變得“多能性”的成體干細胞來進行生產(chǎn),。因為周細胞是利用病人自己的干細胞構(gòu)建出來的,所以它們能夠被移植并且治愈受損組織,,同時不會產(chǎn)生排斥風險,。
Itskovitz-Eldor 教授是瑞本醫(yī)學中心婦產(chǎn)科主任和以色列理工學院干細胞實驗室與福爾曼家庭卓越中心主任(Forman Families Center for Excellence),研究領(lǐng)域是干細胞和組織再生,。
相關(guān)研究發(fā)現(xiàn)近期發(fā)表在美國心臟協(xié)會期刊Circulation上,。(生物谷:towersimper編譯)
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.