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Serum-tolerant polymeric complex for stem-cell transfection and neural differentiation

Author

Listed:
  • Yi Jin

    (China Pharmaceutical University)

  • Guochen Han

    (China Pharmaceutical University)

  • Yuemei Gao

    (China Pharmaceutical University)

  • Hao Cheng

    (China Pharmaceutical University)

  • Chenhua Sun

    (China Pharmaceutical University)

  • Jiang Ni

    (Affiliated Hospital of Jiangnan University)

  • Jianping Zhou

    (China Pharmaceutical University)

  • Huaqing Zhang

    (China Pharmaceutical University)

  • Yang Ding

    (China Pharmaceutical University)

Abstract

Mesenchymal stem cell (MSC) therapy holds promise in biomedical applications but faces challenges in efficient transfection without compromising cell viability. Here, we show a serum-tolerant MSC transfection nanotool, APOs@BP, composed of an apolipoprotein (APO) corona and a boronated polyethyleneimine (BP) core. The APOs corona’s serum-protein resistance and cytomembrane affinity enable APOs@BP to achieve 10.4-fold higher transfection efficiency and improved cytocompatibility in serum-containing medium compared to high-molecular-weight polycationic transfectants. For MSC neural differentiation, miRNA-124 and all-trans retinoic acid derivative (atRAN) are further loaded into APOs@BP, forming a polymeric complex for sequential drug release triggered by lysosomal acid and cytosolic reactive oxygen species post-transplantation. Transcriptomic analysis confirms that this system enhances MSC neural differentiation through sequential activation of atRAN-induced differentiation potential and miRNA-124-directed neurogenesis via cGMP-PKG, MAPK, and PI3K-Akt pathways. Transplantation of engineered MSCs reconstructs neural circuits and alleviates cognitive impairment in Alzheimer’s disease model mice. Collectively, this system provides a robust and convenient method for MSC-based regenerative medicine.

Suggested Citation

  • Yi Jin & Guochen Han & Yuemei Gao & Hao Cheng & Chenhua Sun & Jiang Ni & Jianping Zhou & Huaqing Zhang & Yang Ding, 2025. "Serum-tolerant polymeric complex for stem-cell transfection and neural differentiation," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57278-8
    DOI: 10.1038/s41467-025-57278-8
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    References listed on IDEAS

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    1. Raquel Ferreira & Joseph Napoli & Tariq Enver & Liliana Bernardino & Lino Ferreira, 2020. "Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    2. Mingyang Li & Xinyang Jin & Tao Liu & Feng Fan & Feng Gao & Shuang Chai & Lihua Yang, 2022. "Nanoparticle elasticity affects systemic circulation lifetime by modulating adsorption of apolipoprotein A-I in corona formation," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Martin P. Stewart & Armon Sharei & Xiaoyun Ding & Gaurav Sahay & Robert Langer & Klavs F. Jensen, 2016. "In vitro and ex vivo strategies for intracellular delivery," Nature, Nature, vol. 538(7624), pages 183-192, October.
    4. Yunqiu Miao & Lijun Li & Ying Wang & Jiangyue Wang & Yihan Zhou & Linmiao Guo & Yanqi Zhao & Di Nie & Yang Zhang & Xinxin Zhang & Yong Gan, 2024. "Regulating protein corona on nanovesicles by glycosylated polyhydroxy polymer modification for efficient drug delivery," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
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