Endothelial differentiation of adipose-derived stem cells: effects of endothelial cell growth supplement and shear force.
Endothelial differentiation of adipose-derived stem cells: effects of endothelial cell growth supplement and shear force.
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DOI：
10.1016/j.jss.2008.06.029
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发表时间：
2009-03
影响因子：
2.2
通讯作者：
DiMuzio, Paul J.
中科院分区：
文献类型：
--
作者：
Fischer, Lauren J.;McIlhenny, Stephen;Tulenko, Thomas;Tulenko, Thomas;Golesorkhi, Negar;Zhang, Ping;Larson, Robert;Lombardi, Joseph;Shapiro, Irving;DiMuzio, Paul J.
关键词：
脂肪组织是用于组织工程/再生医学的多能成体干细胞的容易获得的来源。各种生长因子已被用于刺激脂肪源性干细胞（ASC）获得内皮特征。本文研究了内皮细胞生长因子（ECGS）和生理剪切力对ASC向内皮细胞分化的影响。从脐周脂肪中分离人ASC（CD13 + 29 + 90 + 31 − 45 −），在ECGS培养基中培养（长达3周），并在体外暴露于生理剪切力（12达因，长达8天）。通过基质胶上的索形成、乙酰化低密度脂蛋白（acLDL）摄取以及一氧化氮合酶（eNOS）、血管性血友病因子（vWF）和CD 31（PECAM）的表达来定义内皮表型。此外，通过将犬自体ASC接种到植入犬动脉循环内的血管移植物上两周来评价细胞促凝性。我们发现，未分化的ASC没有显示任何的内皮特征。在ECGS中培养后，ASC在Matrigel中形成条索，但不能摄取acLDL或表达分子标记。随后暴露于剪切导致干细胞重新排列，acLDL摄取和CD31表达; eNOS和vWF表达仍未观察到。在ECGS（±剪切）中生长的细胞接种的移植物在2周时保持通畅（7个中的6个），但沿管腔表面有一层薄的纤维蛋白沿着。这项研究表明：1）ECGS和剪切促进人脂肪源性干细胞中几种内皮特征的表达，但不促进eNOS或vWF的表达，2）它们的联合作用似乎是协同的，3）在ECGS中分化的干细胞在体内出现轻度血栓形成，可能部分与eNOS表达不足有关。因此，虽然通过源自脂肪组织的成体干细胞获得几种内皮特征表明这些细胞是用于心血管再生的自体细胞的可行来源，但在将它们用作真正的内皮细胞替代物之前，需要进一步的刺激/修饰。
Adipose tissue is a readily available source of multipotent adult stem cells for use in tissue engineering/regenerative medicine. Various growth factors have been used to stimulate acquisition of endothelial characteristics by adipose-derived stem cells (ASC). Herein we study the effects of endothelial cell growth supplement (ECGS) and physiologic shear force on the differentiation of ASC into endothelial cells. Human ASC (CD13+29+90+31−45−) were isolated from peri-umbilical fat, cultured in ECGS media (for up to three weeks) and exposed to physiological shear force (12 dynes for up to eight days) in vitro. Endothelial phenotype was defined by cord formation on Matrigel, acetylated-LDL (acLDL) uptake, and expression of nitric oxide synthase (eNOS), von Willebrand factor (vWF), and CD31 (PECAM). Additionally, cell thrombogenicity was evaluated by seeding canine autologous ASC onto vascular grafts implanted within the canine arterial circulation for two weeks. We found that undifferentiated ASC did not display any of the noted endothelial characteristics. After culture in ECGS, ASC formed cords in Matrigel, but failed to take up acLDL or express the molecular markers. Subsequent exposure to shear resulted in stem cell realignment, acLDL uptake and expression of CD31; eNOS and vWF expression was still not observed. Grafts seeded with cells grown in ECGS (±shear) remained patent (six of seven) at two weeks but had a thin coat of fibrin along the luminal surfaces. This study suggests that: 1) ECGS and shear promote the expression of several endothelial characteristics in human adipose-derived stem cells, but not eNOS or vWF, 2) their combined effects appear synergistic, and 3) stem cells differentiated in ECGS appear mildly thrombogenic in vivo, possibly related, in part, to insufficient eNOS expression. Thus, while the acquisition of several endothelial characteristics by adult stem cells derived from adipose tissue suggests these cells are a viable source of autologous cells for cardiovascular regeneration, further stimulation/modifications are necessary prior to using them as a true endothelial cell replacement.
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影响因子：
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作者：
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