2. Academic Validation
  3. A scalable platform for EPSC-Induced MSC extracellular vesicles with therapeutic potential

A scalable platform for EPSC-Induced MSC extracellular vesicles with therapeutic potential

  • Stem Cell Res Ther. 2025 Aug 5;16(1):426. doi: 10.1186/s13287-025-04507-y.
Shixin Gong 1,  Nan Li 2,  Qinqing Peng 2,  Feng Wang 2,  Rulong Du 2,  Boyang Zhang 2,  Jian Wang 2,  Le Han 2,  Yu Zhang 2,  Zemin Ning 3,  Shengjiang Tan 4 5 6,  Yuchun Gu 7 8,  Lida Wu 9
Affiliations

Affiliations

  • 1 Allife Medicine Co., Ltd, No. 22, Jinyuan Road, Economic Development Zone, Daxing District, Beijing, 100053, China. gongshixin@allifetech.com.
  • 2 Allife Medicine Co., Ltd, No. 22, Jinyuan Road, Economic Development Zone, Daxing District, Beijing, 100053, China.
  • 3 The Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
  • 4 Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Keith Peters Building, Hills Rd, Cambridge, CB2 0XY, UK.
  • 5 Department of Haematology, Jeffrey Cheah Biomedical Centre, University of Cambridge School of Clinical Medicine, Puddicombe Way, Cambridge Biomedical Campus, Cambridge, CB2 0AW, UK.
  • 6 Jeffrey Cheah Biomedical Centre, Wellcome Trust-Medical Research Council Stem Cell Institute, Puddicombe Way, Cambridge Biomedical Campus, Cambridge, CB2 0AW, UK.
  • 7 Allife Medicine Co., Ltd, No. 22, Jinyuan Road, Economic Development Zone, Daxing District, Beijing, 100053, China. ycgu@pku.edu.cn.
  • 8 Molecular Pharmacology Laboratory, Institute of Molecular Medicine, Peking University, Beijing, 100091, China. ycgu@pku.edu.cn.
  • 9 Allife Medicine Co., Ltd, No. 22, Jinyuan Road, Economic Development Zone, Daxing District, Beijing, 100053, China. wldpaper@pku.edu.cn.
PMID: 40765003 DOI: 10.1186/s13287-025-04507-y
Abstract

Background: Extracellular Vesicles (EVs) derived from mesenchymal stem cells (MSCs) have gained recognition as promising therapeutic and drug delivery agents in regenerative medicine. However, their clinical application is limited by donor variability, low scalability, and inconsistent therapeutic quality. To overcome these challenges, a robust and standardized production platform is urgently needed.

Methods: We developed a scalable biomanufacturing strategy by generating and expanding MSCs from extended pluripotent stem cells (EPSC) using a suspension bioreactor culture system. A fixed-bed bioreactor was integrated for automated, continuous expansion of iMSCs and downstream EV harvesting. EVs were isolated through a streamlined protocol and characterized for size, morphology, surface markers, and bioactivity. Therapeutic efficacy was assessed in a bleomycin-induced pulmonary fibrosis mouse model.

Results: iMSC-derived EVs (iMSC-EVs) exhibited comparable characteristics to primary MSC-EVs, including a size distribution of 70-80 nm, cup-shaped morphology, and expression of canonical EV markers (CD63, CD81, TSG101). iMSCs were expanded for up to 20 days in 3D culture, yielding > 5 × 10⁸ cells per batch using a suspension bioreactor culture system and producing ~ 1.2 × 10¹³ EV particles/day in a fixed-bed bioreactor. In vivo, iMSC-EVs significantly reduced Ashcroft fibrosis scores and bronchoalveolar lavage fluid protein levels in bleomycin-injured lungs, with therapeutic efficacy comparable to primary MSC-EVs.

Conclusions: This study establishes a scalable and standardized platform for producing high-quality iMSC-EVs using bioreactor-based systems. Our approach addresses key limitations in traditional EV production and sets the stage for AI-integrated, fully automated, GMP-compliant manufacturing of therapeutic EVs suitable for clinical translation.

Keywords

Extended pluripotent stem cells; Extracellular vesicles; Induced mesenchymal stem cells; Pulmonary fibrosis therapy; Regenerative medicine; Scalable biomanufacturing.

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