Nakayama Karina H, Joshi Prajakta A, Lai Edwina S, Gujar Prachi, Joubert Lydia-M, Chen Bertha, Huang Ngan F
Stanford Cardiovascular Institute, Stanford University, Stanford, CA 94305, USA.
Department of Cardiothoracic Surgery, Stanford University, 300 Pasteur Drive, Stanford, CA 94305-5407, USA.
Regen Med. 2015;10(6):745-55. doi: 10.2217/rme.15.45. Epub 2015 Oct 6.
We developed an aligned bi-layered vascular graft derived from human induced pluripotent stem cells (iPSCs) that recapitulates the cellular composition, orientation, and anti-inflammatory function of blood vessels.
MATERIALS & METHODS: The luminal layer consisted of longitudinal-aligned nanofibrillar collagen containing primary endothelial cells (ECs) or iPSC-derived ECs (iPSC-ECs). The outer layer contained circumferentially oriented nanofibrillar collagen with primary smooth muscle cells (SMCs) or iPSC-derived SMCs(iPSC-SMCs).
On the aligned scaffolds, cells organized F-actin assembly within 8º from the direction of nanofibrils. When compared to randomly-oriented scaffolds, EC-seeded aligned scaffolds had significant reduced inflammatory response, based on adhesivity to monocytes.
This study highlights the importance of anisotropic scaffolds in directing cell form and function, and has therapeutic significance as physiologically relevant blood vessels.
我们研发了一种源自人诱导多能干细胞(iPSC)的对齐双层血管移植物,该移植物重现了血管的细胞组成、取向和抗炎功能。
管腔层由含有原代内皮细胞(EC)或iPSC衍生的内皮细胞(iPSC-EC)的纵向对齐的纳米纤维胶原组成。外层包含具有原代平滑肌细胞(SMC)或iPSC衍生的平滑肌细胞(iPSC-SMC)的周向取向纳米纤维胶原。
在对齐的支架上,细胞在距纳米纤维方向8°范围内组织F-肌动蛋白组装。与随机取向的支架相比,基于对单核细胞的粘附性,接种EC的对齐支架的炎症反应显著降低。
本研究强调了各向异性支架在指导细胞形态和功能方面的重要性,并且作为生理相关血管具有治疗意义。