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

Author:

Feng Lin1234,Li Da125,Tian Yao1234,Zhao Chengshun1234,Sun Yun125,Kou Xiaolong256,Wu Jun1235,Wang Liu1245,Gu Qi256,Li Wei1235,Hao Jie1235,Hu Baoyang1235ORCID,Wang Yukai1235ORCID

Affiliation:

1. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China

2. Institute for Stem Cell and Regenerative Medicine, Chinese Academy of Sciences, Beijing, China

3. National Stem Cell Resource Center, Chinese Academy of Sciences, Beijing, China

4. Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China

5. Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China

6. State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China

Abstract

Abstract JOURNAL/nrgr/04.03/01300535-202402000-00041/inline-graphic1/v/2023-07-19T141749Z/r/image-tiff 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.

Publisher

Medknow

Subject

Developmental Neuroscience

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