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

Yi Jin, Guochen Han, Yuemei Gao, Hao Cheng, Chenhua Sun, Jiang Ni, Jianping Zhou (), Huaqing Zhang () and Yang Ding ()
Additional contact information
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

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: 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.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-57278-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57278-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-57278-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().