Vascular smooth muscle cells derived from inbred swine induced pluripotent stem cells for vascular tissue engineering.
Vascular smooth muscle cells derived from inbred swine induced pluripotent stem cells for vascular tissue engineering.
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DOI：
10.1016/j.biomaterials.2017.09.019
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发表时间：
2017-12
期刊：
影响因子：
14
通讯作者：
Qyang Y
中科院分区：
文献类型：
--
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
使用源自人诱导多能干细胞（iPSC）的血管平滑肌细胞（VSMC）开发自体组织工程化血管构建物在治疗患有血管疾病的患者方面具有巨大潜力。然而，在临床应用之前，需要基于iPSC的大型动物细胞和组织模型来评估安全性和有效性。在本文中，通过将多西环素诱导的重编程因子引入来自近交系马萨诸塞州综合医院小型猪的胎儿成纤维细胞中来建立猪iPSC（siPSC）系，所述小型猪接受组织和器官移植而在系内没有免疫抑制。高度富集的功能性VSMC来源于siPSC，其基于添加抗坏血酸和通过多西环素撤回使重编程因子失活。此外，siPSC-VSMC接种到可生物降解的聚乙醇酸（PGA）支架上容易形成血管组织，将其皮下植入免疫缺陷小鼠，并显示出进一步成熟的成熟VSMC标志物，平滑肌肌球蛋白重链的表达。最后，使用一种强大的细胞自组装方法，我们从siPSC-VSMCs开发了3D无支架组织环，其显示出与从猪原代VSMCs开发的那些相当的机械性能和收缩功能。这些由多西环素诱导的近交siPSC制备的工程化血管构建体为临床前研究用于患者治疗的基于自体人iPSC的血管组织提供了新的机会。
Development of autologous tissue-engineered vascular constructs using vascular smooth muscle cells (VSMCs) derived from human induced pluripotent stem cells (iPSCs) holds great potential in treating patients with vascular disease. However, preclinical, large animal iPSC-based cellular and tissue models are required to evaluate safety and efficacy prior to clinical application. Herein, swine iPSC (siPSC) lines were established by introducing doxycycline-inducible reprogramming factors into fetal fibroblasts from a line of inbred Massachusetts General Hospital miniature swine that accept tissue and organ transplants without immunosuppression within the line. Highly enriched, functional VSMCs were derived from siPSCs based on addition of ascorbic acid and inactivation of reprogramming factor via doxycycline withdrawal. Moreover, siPSC-VSMCs seeded onto biodegradable polyglycolic acid (PGA) scaffolds readily formed vascular tissues, which were implanted subcutaneously into immunodeficient mice and showed further maturation revealed by expression of the mature VSMC marker, smooth muscle myosin heavy chain. Finally, using a robust cellular self-assembly approach, we developed 3D scaffold-free tissue rings from siPSC-VSMCs that showed comparable mechanical properties and contractile function to those developed from swine primary VSMCs. These engineered vascular constructs, prepared from doxycycline-inducible inbred siPSCs, offer new opportunities for preclinical investigation of autologous human iPSC-based vascular tissues for patient treatment.
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影响因子：
37.8
作者：
Go AS;Mozaffarian D;Roger VL;Benjamin EJ;Berry JD;Blaha MJ;Dai S;Ford ES;Fox CS;Franco S;Fullerton HJ;Gillespie C;Hailpern SM;Heit JA;Howard VJ;Huffman MD;Judd SE;Kissela BM;Kittner SJ;Lackland DT;Lichtman JH;Lisabeth LD;Mackey RH;Magid DJ;Marcus GM;Marelli A;Matchar DB;McGuire DK;Mohler ER 3rd;Moy CS;Mussolino ME;Neumar RW;Nichol G;Pandey DK;Paynter NP;Reeves MJ;Sorlie PD;Stein J;Towfighi A;Turan TN;Virani SS;Wong ND;Woo D;Turner MB;American Heart Association Statistics Committee and Stroke Statistics Subcommittee
通讯作者：
American Heart Association Statistics Committee and Stroke Statistics Subcommittee
影响因子：
4.8
作者：
Esteban, Miguel A.;Xu, Jianyong;Pei, Duanqing
通讯作者：
Pei, Duanqing
影响因子：
44.1
作者：
Moon, Jai-Hee;Heo, June Seok;You, Seungkwon
通讯作者：
You, Seungkwon
影响因子：
6.2
作者：
Mezrich, JD;Haller, GW;Sachs, DH
通讯作者：
Sachs, DH
影响因子：
20.1
作者：
Gu M;Nguyen PK;Lee AS;Xu D;Hu S;Plews JR;Han L;Huber BC;Lee WH;Gong Y;de Almeida PE;Lyons J;Ikeno F;Pacharinsak C;Connolly AJ;Gambhir SS;Robbins RC;Longaker MT;Wu JC
通讯作者：
Wu JC