Recently, the team of Jianping Zhou/Yang Ding/Huaqing Zhang from the School of Pharmacy of the University of China published the latest research results entitled Serum-tolerant polymeric complex for stem-cell transfection and neural differentiation in the authoritative journal Nature Communications. The latest research results. Professor Zhou Jianping, Professor Ding Yang and Associate Researcher Zhang Huaqing are the co-corresponding authors of the paper, while Jin Yi, a PhD student of the class of 2021, and Han Guochen, a postdoctoral fellow and a PhD graduate of the class of 2024, are the co-first authors, and China Pharmaceutical University (CPU) is the first corresponding institution of the paper.
In recent years, the irreversible nerve damage/loss challenges surrounding central diseases can be used for the treatment of many neurodegenerative diseases, including Alzheimer's disease (AD), through neural directed differentiation and cell network reconstruction. However, its efficacy is still limited by bottlenecks such as insufficient stem cell transfection efficiency, low cell survival, and difficult neural differentiation. To address the above scientific issues, the present results propose for the first time a serum-resistant stem cell transfection technique based on endogenous apolipoproteins (APOs), combined with a heterodrug dual-loading strategy, which successfully achieves efficient neural differentiation of stem cells.
By resolving the functional components of protein crowns and introducing APOs modifications, the research team developed a stem cell transfection nanosystem (APOs@BP) with both serum tolerance and membrane affinity, successfully realising safe and efficient stem cell transfection under serum-containing culture conditions. Based on this, to meet the demand of neural differentiation time-sequence regulation of stem cells, we co-loaded all-trans retinoic acid derivatives and endogenous neurogenic key factor miR-124, and activated the differentiation potential and neurogenic pathway of MSCs sequentially by using the pH/ROS-responsive time-sequence release mechanism, to provide new ideas and new solutions for the treatment of central system diseases, such as AD. This provides new ideas and solutions for the treatment of AD and other central system diseases.
The team has long been committed to innovative stem cell preparations and natural active particles for the multi-dimensional prevention and treatment of AD, and has published three authoritative and several top papers in PNAS, Nat Commun, Adv Mater, Nano Lett, Adv Sci. and J Control Release journals, and has obtained five relevant invention patents, looking forward to more research cooperation and translation. We are looking forward to more research collaborations and translations.
The above work has been supported by the National High-level Young Talents Support Programme, the National Natural Science Foundation of China, the Outstanding Youth Fund of Jiangsu Province, the Natural Science Foundation of Jiangsu Province, the Basic Operating Expenses of China Pharmaceutical University, and the ‘Double First-class’ Construction Plan.
Original Link：https://www.nature.com/articles/s41467-025-57278-8
Diagram of Engineered stem cell construction and AD therapy based on stem cell serum-resistant transfection technology
