Xenogeneic-free generation of vascular smooth muscle cells from human induced pluripotent stem cells for vascular tissue engineering.

Xenogeneic-free generation of vascular smooth muscle cells from human induced pluripotent stem cells for vascular tissue engineering.
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DOI:
10.1016/j.actbio.2020.10.042
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发表时间:
2021-01-01
期刊:
影响因子:
9.7
通讯作者:
Qyang Y
Qyang Y
中科院分区:
工程技术1区
文献类型:
--
作者:
Luo J;Lin Y;Shi X;Li G;Kural MH;Anderson CW;Ellis MW;Riaz M;Tellides G;Niklason LE;Qyang Y

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从人诱导多能干细胞(hiPSC)衍生的血管平滑肌细胞(hiPSC-VSMC)开发机械先进的组织工程化血管移植物(TEVG)提供了替代或绕过患病血管的创新方法。为了将目前的hiPSC-TEVG推向临床应用,必须在无异种条件下获得hiPSC-VSMC衍生的组织,这意味着不使用任何动物源性试剂。已经报道了hiPSC的VSMC分化的许多方法,尽管尚未建立用于产生适合于血管组织工程的hiPSC-VSMC的无异种的方法。基于我们先前建立的异种VSMC分化的标准方法,我们用人源的功能性对应物替换了所有动物源性试剂,并成功地衍生出功能性无异种hiPSC-VSMC(XF-hiPSC-VSMC)。接下来,我们的小组通过细胞自组装从XF-hiPSC-VSMC开发了组织环,其表现出与从异种hiPSC-VSMC开发的那些相当的机械强度。此外,通过将XF-hiPSC-VSMC接种到可生物降解的聚乙醇酸(PGA)支架上,我们产生了呈现有效胶原沉积的工程化血管组织,其适合植入免疫缺陷小鼠模型中。总之,我们用于产生hiPSC-VSMC的无异种条件产生具有与标准异种方案相当的血管组织工程能力的细胞,从而使hiPSC-TEVG技术更接近安全有效的临床转化。
Development of mechanically advanced tissue-engineered vascular grafts (TEVGs) from human induced pluripotent stem cell (hiPSC)-derived vascular smooth muscle cells (hiPSC-VSMCs) offers an innovative approach to replace or bypass diseased blood vessels. To move current hiPSC-TEVGs toward clinical application, it is essential to obtain hiPSC-VSMC-derived tissues under xenogeneic-free conditions, meaning without the use of any animal-derived reagents. Many approaches in VSMC differentiation of hiPSCs have been reported, although a xenogeneic-free method for generating hiPSC-VSMCs suitable for vascular tissue engineering has yet to be established. Based on our previously established standard method of xenogeneic VSMC differentiation, we have replaced all animal-derived reagents with functional counterparts of human origin and successfully derived functional xenogeneic-free hiPSC-VSMCs (XF-hiPSC-VSMCs). Next, our group developed tissue rings via cellular self-assembly from XF-hiPSC-VSMCs, which exhibited comparable mechanical strength to those developed from xenogeneic hiPSC-VSMCs. Moreover, by seeding XF-hiPSC-VSMCs onto biodegradable polyglycolic acid (PGA) scaffolds, we generated engineered vascular tissues presenting effective collagen deposition which were suitable for implantation into an immunodeficient mice model. In conclusion, our xenogeneic-free conditions for generating hiPSC-VSMCs produce cells with the comparable capacity for vascular tissue engineering as standard xenogeneic protocols, thereby moving the hiPSC-TEVG technology one step closer to safe and efficacious clinical translation.
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