Harnessing 3D cultured MSC exosomes through tangential flow filtration for enhanced diabetic wound healing

作者：Yanmei Chen, Yang Xu, Yali Zheng, Yingda Yan, Jiawei Cai, Chu Hua, Jiang Li, Cheng Zhang, Marianne Lauwers, Ying Rao, Zhenyu Zhong, Dai Fei Elmer Ker, Rocky S. Tuan, Xiao Yang, Dan Wang, Zhiyong Zhang · 发表于：Stem Cells Translational Medicine · 年份：2025 · DOI：10.1093/stcltm/szaf064 · 被引用次数：6 · 研究领域：Extracellular vesicles in disease、Wound Healing and Treatments、Tissue Engineering and Regenerative Medicine

INTRODUCTION: Mesenchymal stem cell-derived exosomes have garnered considerable attention in regenerative medicine due to their non-immunogenicity, low infusion toxicity, easy accessibility, straightforward preservation, and minimal ethical concerns. While ultracentrifugation is the prevailing method for high-purity exosome isolation, it is limited by low throughput and the need for specialized infrastructure. This study investigates tangential flow filtration (TFF) as a promising alternative for exosome isolation. This technique offers simpler operation, higher yields, and improved recovery rates compared to ultracentrifugation. METHODS: Human umbilical cord mesenchymal stem cells (hUCMSCs) were cultured in a 3D microcarrier-bioreactor system, and exosomes were extracted from the conditioned medium using either ultracentrifugation or an automated and enclosed TFF system. Subsequently, we compared the quantity, quality and therapeutic efficacy of the exosomes isolated via both approaches, evaluating their effects in vitro and in a mouse model of diabetic wound healing. RESULTS: Our findings demonstrate that the TFF method effectively isolates high-quality exosomes that meet the standards set by the Minimum Information for Studies of Extracellular Vesicles (MISEV) 2023 guidelines, while achieving a significantly higher extraction yield compared to the traditional ultracentrifugation. Furthermore, both TFF and ultracentrifugation-derived exosomes demonstrate comparable biologic...