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脂肪来源间充质基质细胞(ADSCs)衬里假体移植促进猴和猪的血管再生。

Implantation of Adipose-Derived Mesenchymal Stromal Cells (ADSCs)-Lining Prosthetic Graft Promotes Vascular Regeneration in Monkeys and Pigs.

机构信息

Regenerative Medicine Research Center, Sichuan University West China Hospital, Chengdu, 610093, China.

Sichuan 3D Bioprinting Institute, Chengdu, China.

出版信息

Tissue Eng Regen Med. 2024 Jun;21(4):641-651. doi: 10.1007/s13770-023-00615-z. Epub 2024 Jan 8.

Abstract

BACKGROUND

Current replacement procedures for stenosis or occluded arteries using prosthetic grafts have serious limitations in clinical applications, particularly, endothelialization of the luminal surface is a long-standing unresolved problem.

METHOD

We produced a cell-based hybrid vascular graft using a bioink engulfing adipose-derived mesenchymal stromal cells (ADSCs) and a 3D bioprinting process lining the ADSCs on the luminal surface of GORE-Tex grafts. The hybrid graft was implanted as an interposition conduit to replace a 3-cm-long segment of the infrarenal abdominal aorta in Rhesus monkeys.

RESULTS

Complete endothelium layer and smooth muscle layer were fully developed within 21 days post-implantation, along with normalized collagen deposition and crosslinking in the regenerated vasculature in all monkeys. The regenerated blood vessels showed normal functionality for the longest observation of more than 1650 days. The same procedure was also conducted in miniature pigs for the interposition replacement of a 10-cm-long right iliac artery and showed the same long-term effective and safe outcome.

CONCLUSION

This cell-based vascular graft is ready to undergo clinical trials for human patients.

摘要

背景

目前使用人工移植物来治疗狭窄或闭塞的动脉存在严重的临床应用局限性,特别是腔内表面的内皮化仍然是一个长期未解决的问题。

方法

我们使用一种生物墨水包裹脂肪间充质基质细胞(ADSCs)并通过 3D 生物打印技术将 ADSCs 排列在 GORE-TEX 移植物的腔面,制备了一种基于细胞的杂交血管移植物。将杂交移植物作为间置导管,植入恒河猴的肾下腹部主动脉 3cm 长的节段以进行替换。

结果

所有猴子在移植后 21 天内完全形成了完整的内皮细胞层和平滑肌层,同时在新生血管中也有正常的胶原沉积和交联。在最长超过 1650 天的观察中,再生血管显示出正常的功能。同样的程序也在小型猪中进行了 10cm 长右侧髂动脉的间置替换,也显示出同样的长期有效和安全的结果。

结论

这种基于细胞的血管移植物已经准备好进行人体临床试验。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/659b/11087433/b17b679f21ba/13770_2023_615_Fig1_HTML.jpg

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