期刊
STEM CELLS AND DEVELOPMENT
卷 30, 期 5, 页码 247-264出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/scd.2020.0206
关键词
pancreas; mesenchymal stromal cells; extracellular vesicles; proteomics; regenerative medicine; transplantation
资金
- Canadian Institute of Health Research (CIHR MOP) [378189, 426890]
- Juvenile Diabetes Research Foundation [2-SRA-2015-60-Q-R]
- NSERC
- Canadian Foundation for Innovation
The study demonstrates that intrapancreatic injection of concentrated CM produced by MSCs can support islet regeneration and glycemic control. Using Panc-MSC as biofactories, the research shows potential applications for regenerative medicine by enriching tissue regenerative stimuli housed within the secretome.
The secretome of mesenchymal stromal cells (MSCs) is enriched for biotherapeutic effectors contained within and independent of extracellular vesicles (EVs) that may support tissue regeneration as an injectable agent. We have demonstrated that the intrapancreatic injection of concentrated conditioned media (CM) produced by bone marrow MSC supports islet regeneration and restored glycemic control in hyperglycemic mice, ultimately providing a platform to elucidate components of the MSC secretome. Herein, we extend these findings using human pancreas-derived MSC (Panc-MSC) as biofactories to enrich for tissue regenerative stimuli housed within distinct compartments of the secretome. Specifically, we utilized 100 kDa ultrafiltration as a simple method to debulk protein mass and to enrich for EVs while concentrating the MSC secretome into an injectable volume for preclinical assessments in murine models of blood vessel and islet regeneration. EV enrichment (EV+) was validated using nanoscale flow cytometry and atomic force microscopy, in addition to the detection of classical EV markers CD9, CD81, and CD63 using label-free mass spectrometry. EV+ CM was predominately enriched with mediators of wound healing and epithelial-to-mesenchymal transition that supported functional regeneration in mesenchymal and nonmesenchymal tissues. For example, EV+ CM supported human microvascular endothelial cell tubule formation in vitro and enhanced the recovery of blood perfusion following intramuscular injection in nonobese diabetic/severe combined immunodeficiency mice with unilateral hind limb ischemia. Furthermore, EV+ CM increased islet number and beta cell mass, elevated circulating insulin, and improved glycemic control following intrapancreatic injection in streptozotocin-treated mice. Collectively, this study provides foundational evidence that Panc-MSC, readily propagated from the subculture of human islets, may be utilized for regenerative medicine applications.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据