Efficient Differentiation of Human Induced Pluripotent Stem Cells into Endothelial Cells under Xenogeneic-free Conditions for Vascular Tissue Engineering.
Efficient Differentiation of Human Induced Pluripotent Stem Cells into Endothelial Cells under Xenogeneic-free Conditions for Vascular Tissue Engineering.
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DOI：
10.1016/j.actbio.2020.11.007
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发表时间：
2021-01-01
影响因子：
9.7
通讯作者：
Qyang Y
中科院分区：
文献类型：
--
作者：
Luo J;Shi X;Lin Y;Yuan Y;Kural MH;Wang J;Ellis MW;Anderson CW;Zhang SM;Riaz M;Niklason LE;Qyang Y
组织工程血管移植物(TEVGs)为急诊血管介入治疗提供了一种很有前途的治疗选择。尽管体外内皮化所需的较长过程阻碍了使用患者特定的原代内皮细胞(ECs)的小直径TEVGs在植入前预防血栓形成和闭塞的应用，但人诱导多能干细胞(HiPSCs)提供了一个强大的来源来获得免疫相容的ECs(hiPSC-ECs)，用于即刻TEVG内皮化。为了实现临床应用，hPSC-ECs应该在培养条件下获得，而不使用动物衍生的试剂(无异种试剂)，以避免异种试剂产生不必要的宿主免疫反应。然而，以前还没有建立起一种完全无异物的HiPSC-EC产生方法。在此，我们用人类来源的功能试剂取代了异种HIPSC-EC分化的标准方法中使用的动物衍生试剂。因此，我们获得了与人类原代内皮细胞具有相似标记表达和功能的无异种HiPSC-ECs(XF-hiPSC-ECs)。此外，XF-hiPSC-ECs在功能上以典型的细胞排列和基因表达响应剪切力。最后，在动态生物反应器系统中，我们成功地将XF-hiPSC-ECs内皮化脱细胞的人血管。综上所述，我们建立了适合血管组织工程的无异种培养条件，以获得具有功能性的HiPSC-ECs，这将进一步推动TEVG治疗走向临床应用。
Tissue engineered vascular grafts (TEVGs) represent a promising therapeutic option for emergency vascular intervention. Although the application of small-diameter TEVGs using patient-specific primary endothelial cells (ECs) to prevent thrombosis and occlusion prior to implantation could be hindered by the long time course required for in vitro endothelialization, human induced pluripotent stem cells (hiPSCs) provide a robust source to derive immunocompatible ECs (hiPSC-ECs) for immediate TEVG endothelialization. To achieve clinical application, hiPSC-ECs should be derived under culture conditions without the use of animal-derived reagents (xenogeneic-free conditions), to avoid unwanted host immune responses from xenogeneic reagents. However, a completely xenogeneic-free method of hiPSC-EC generation has not previously been established. Herein, we substituted animal-derived reagents used in a standard method of xenogeneic hiPSC-EC differentiation with functional counterparts of human origin. As a result, we generated xenogeneic-free hiPSC-ECs (XF-hiPSC-ECs) with similar marker expression and function to those of human primary ECs. Furthermore, XF-hiPSC-ECs functionally responded to shear stress with typical cell alignment and gene expression. Finally, we successfully endothelialized decellularized human vessels with XF-hiPSC-ECs in a dynamic bioreactor system. In conclusion, we developed xenogeneic-free conditions for generating functional hiPSC-ECs suitable for vascular tissue engineering, which will further move TEVG therapy toward clinical application.
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DOI：
10.1083/jcb.201408103
发表时间：
2015-03-30
期刊：
The Journal of cell biology
影响因子：
--
作者：
Coon BG;Baeyens N;Han J;Budatha M;Ross TD;Fang JS;Yun S;Thomas JL;Schwartz MA
通讯作者：
Schwartz MA
影响因子：
23.9
作者：
Luo, Jiesi;Qin, Lingfeng;Qyang, Yibing
通讯作者：
Qyang, Yibing
影响因子：
9.7
作者：
Park, Jinkyu;Anderson, Christopher W.;Qyang, Yibing
通讯作者：
Qyang, Yibing
影响因子：
46.9
作者：
Gornalusse GG;Hirata RK;Funk SE;Riolobos L;Lopes VS;Manske G;Prunkard D;Colunga AG;Hanafi LA;Clegg DO;Turtle C;Russell DW
通讯作者：
Russell DW
影响因子：
14
作者：
Luo J;Qin L;Kural MH;Schwan J;Li X;Bartulos O;Cong XQ;Ren Y;Gui L;Li G;Ellis MW;Li P;Kotton DN;Dardik A;Pober JS;Tellides G;Rolle M;Campbell S;Hawley RJ;Sachs DH;Niklason LE;Qyang Y
通讯作者：
Qyang Y