Neural Regeneration Research ›› 2024, Vol. 19 ›› Issue (2): 458-464.doi: 10.4103/1673-5374.377412

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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

Lin Feng1, 2, 3, 4, #, Da Li1, 2, 5, #, Yao Tian1, 2, 3, 4, Chengshun Zhao1, 2, 3, 4, Yun Sun1, 2, 5, Xiaolong Kou2, 5, 6, Jun Wu1, 2, 3, 5, Liu Wang1, 2, 4, 5, Qi Gu2, 5, 6, Wei Li1, 2, 3, 5, Jie Hao1, 2, 3, 5, Baoyang Hu1, 2, 3, 5, *, Yukai Wang1, 2, 3, 5, *   

  1. 1State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China; 2Institute for Stem Cell and Regenerative Medicine, Chinese Academy of Sciences, Beijing, China; 3National Stem Cell Resource Center, Chinese Academy of Sciences, Beijing, China; 4Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China; 5Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China; 6State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
  • Online:2024-02-15 Published:2023-08-30
  • Contact: Baoyang Hu, PhD, byhu@ioz.ac.cn; Yukai Wang, PhD, wangyukai@ioz.ac.cn.
  • Supported by:
    This study was supported by the National Key Research and Development Program of China, Nos. 2017YFE0122900 (to BH), 2019YFA0110800 (to WL), 2019YFA0903802 (to YW), 2021YFA1101604 (to LW), 2018YFA0108502 (to LF), and 2020YFA0804003 (to JW); the National Natural Science Foundation of China, Nos. 31621004 (to WL, BH) and 31970821 (to YW); CAS Project for Young Scientists in Basic Research, No. YSBR-041 (to YW); and Joint Funds of the National Natural Science Foundation of China, No. U21A20396 (to BH).

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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.

Key words: axonal integrity, cell cryopreservation, cellular environment, cellular niche, cell replacement therapy, dopaminergic progenitors, human pluripotent stem cell, mechanical damage, neuronal cell delivery, Parkinson’s disease, small-aperture gelatin microcarriers