title: In Vivo Differentiation of Therapeutic Insulin-Producing Cells from Bone Marrow Cells via Extracellular Vesicle-Mimetic Nanovesicles.
abstract: The current diabetes mellitus pandemic constitutes an important global health problem. Reductions in the mass and function of β-cells contribute to most of the pathophysiology underlying diabetes. Thus, physiological control of blood glucose levels can be adequately restored by replacing functioning β-cell mass. Sources of functional islets for transplantation are limited, resulting in great interest in the development of alternate sources, and recent progress regarding cell fate change via utilization of extracellular vesicles, also known as exosomes and microvesicles, is notable. Thus, this study investigated the therapeutic capacity of extracellular vesicle-mimetic nanovesicles (NVs) derived from a murine pancreatic β-cell line. To differentiate insulin-producing cells effectively, a three-dimensional in vivo microenvironment was constructed in which extracellular vesicle-mimetic NVs were applied to subcutaneous Matrigel platforms containing bone marrow (BM) cells in diabetic immunocompromised mice. Long-term control of glucose levels was achieved over 60 days, and differentiation of donor BM cells into insulin-producing cells in the subcutaneous Matrigel platforms, which were composed of islet-like cell clusters with extensive capillary networks, was confirmed along with the expression of key pancreatic β-cell markers. The resectioning of the subcutaneous Matrigel platforms caused a rebound in blood glucose levels and confirmed the source of functioning β-cells. Thus, efficient differentiation of therapeutic insulin-producing cells was attained in vivo through the use of extracellular vesicle-mimetic NVs, which maintained physiological glucose levels.
authors.forename: Keunhee
authors.initials: K
authors.lastname: Oh
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology , Pohang, Gyeongbuk 37673, Korea.
authors.forename: Sae Rom
authors.initials: SR
authors.lastname: Kim
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology , Pohang, Gyeongbuk 37673, Korea.
authors.forename: Dae-Kyum
authors.initials: DK
authors.lastname: Kim
authors.forename: Myung Won
authors.initials: MW
authors.lastname: Seo
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology , Pohang, Gyeongbuk 37673, Korea.
authors.forename: Changjin
authors.initials: C
authors.lastname: Lee
authors.affiliation: Biomedical Research Institute, Seoul National University Hospital , Seoul 110-744, Korea.
authors.forename: Hak Mo
authors.initials: HM
authors.lastname: Lee
authors.affiliation: Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University , Seoul 110-799, Korea.
authors.forename: Ju-Eun
authors.initials: JE
authors.lastname: Oh
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Choi
authors.forename: Dong-Sup
authors.initials: DS
authors.lastname: Lee
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology , Pohang, Gyeongbuk 37673, Korea.
authors.forename: Yong Song
authors.initials: YS
authors.lastname: Gho
authors.affiliation: Biomedical Research Institute, Seoul National University Hospital , Seoul 110-744, Korea.|Department of Internal Medicine, Seoul National University College of Medicine , Seoul 110-799, Korea.|Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University , Seoul 110-799, Korea.
authors.forename: Kyong Soo
authors.initials: KS
authors.lastname: Park
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D040761:Biomimetic Materials / Q000737:chemistry / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D055354:Exosomes / Q000737:chemistry*; D005947:Glucose / Q000032:analysis / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D041681:NIH 3T3 Cells; D049329:Nanostructures / Q000737:chemistry*
chemical_list: D007328:Insulin; D005947:Glucose
keywords: diabetes; exosome; exosome-mimetic; mesenchymal stem cell; regenerative medicine; β-cell differentiation