One-step cell biomanufacturing platform: porous gelatin microcarrier beads promote human embryonic stem cell-derived midbrain dopaminergic progenitor cell differentiation in vitro and survival after transplantation in vivo

一步式细胞生物制造平台:多孔明胶微载体珠促进人胚胎干细胞来源的中脑多巴胺能祖细胞在体外分化,并提高其在体内移植后的存活率

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作者:Lin Feng ,Da Li ,Yao Tian ,Chengshun Zhao ,Yun Sun ,Xiaolong Kou ,Jun Wu ,Liu Wang ,Qi Gu ,Wei Li ,Jie Hao ,Baoyang Hu ,Yukai Wang

Abstract

Numerous studies have shown that cell replacement therapy can replenish lost cells and rebuild neural circuitry in animal models of Parkinson's disease. Transplantation of midbrain dopaminergic progenitor cells is a promising treatment for Parkinson's disease. However, transplanted cells can be injured by mechanical damage during handling and by changes in the transplantation niche. Here, we developed a one-step biomanufacturing platform that uses small-aperture gelatin microcarriers to produce beads carrying midbrain dopaminergic progenitor cells. These beads allow midbrain dopaminergic progenitor cell differentiation and cryopreservation without digestion, effectively maintaining axonal integrity in vitro. Importantly, midbrain dopaminergic progenitor cell bead grafts showed increased survival and only mild immunoreactivity in vivo compared with suspended midbrain dopaminergic progenitor cell grafts. Overall, our findings show that these midbrain dopaminergic progenitor cell beads enhance the effectiveness of neuronal cell transplantation.

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