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基于透明质酸甲基丙烯酰的脂多糖处理间充质干细胞来源的外泌体的微流控包封以恢复小鼠的卵巢功能。

Microfluidic Encapsulation of Exosomes Derived from Lipopolysaccharide-Treated Mesenchymal Stem Cells in Hyaluronic Acid Methacryloyl to Restore Ovarian Function in Mice.

机构信息

Center for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China.

Center for Molecular Reproductive Medicine, Nanjing University, Nanjing, 210008, China.

出版信息

Adv Healthc Mater. 2024 Mar;13(6):e2303068. doi: 10.1002/adhm.202303068. Epub 2023 Nov 16.

DOI:10.1002/adhm.202303068
PMID:37972286
Abstract

Premature ovarian failure (POF) features an upward incidence nowadays, and the human umbilical cord mesenchymal stem cells (hUC-MSCs)-derived exosomes (MSC-Exos) have shown applied values in the recovery of ovarian function. Here, a novel exosome-encapsulated microcarrier prepared by microfluidic technology for ovarian repair after chemotherapy damage is presented. The exosomes derived from lipopolysaccharide (LPS)-preconditioned hUC-MSCs are encapsulated with hyaluronic acid methacryloyl (HAMA) via microfluidic electrospray, which is named HAMA/MSC-Exos. Attributing to the biocompatibility and semipermeable property of HAMA, the encapsulated exosomes show great viability and controllable release behavior from HAMA. It is demonstrated that in situ transplantation of HAMA/MSC-Exos can rescue ovarian functions of cyclophosphamide-induced ovarian failure in mice by increasing ovarian volume, improving the number of antral follicles and restoring fertility. It is believed that the transplantation of HAMA/MSC-Exos will provide a new concept for the treatment of POF in clinical practice.

摘要

卵巢早衰(POF)的发病率呈上升趋势,人脐带间充质干细胞(hUC-MSCs)来源的外泌体(MSC-Exos)在卵巢功能恢复方面显示出了应用价值。本研究采用微流控技术,制备了一种新型的外泌体包裹的微载体,用于化疗损伤后的卵巢修复。通过微流控电喷雾,将脂多糖(LPS)预处理的 hUC-MSCs 来源的外泌体包裹在透明质酸甲基丙烯酰(HAMA)中,命名为 HAMA/MSC-Exos。由于 HAMA 的生物相容性和半透性,包裹的外泌体显示出良好的活力和从 HAMA 中的可控释放行为。研究表明,原位移植 HAMA/MSC-Exos 可以通过增加卵巢体积、增加窦卵泡数量和恢复生育能力来挽救环磷酰胺诱导的卵巢衰竭小鼠的卵巢功能。相信 HAMA/MSC-Exos 的移植将为临床治疗 POF 提供新的概念。

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