title: Microvesicles enhance the mobility of human diabetic adipose tissue-derived mesenchymal stem cells in vitro and improve wound healing in vivo.
abstract: Microvesicles (MVs) derived from mesenchymal stem cells showed the ability to alter the cell phenotype and function. We previously demonstrated that type 2 diabetic adipose tissue-derived mesenchymal stem cells (dAT-MSCs) increase in cell aggregation and adhesion in vitro and impair wound healing in vivo. However, the characterization and function of MVs derived from human non-diabetic AT-MSCs (nAT-MSCs) remain unknown. In this study, we characterized nAT-MSC-derived MVs and their function after the transfection of dAT-MSCs with MVs using the scratch assay and a flap mouse model. We found that human nAT-MSC-derived MVs expressed MSC-surface markers and improved dAT-MSC functions by altering the expression of genes associated with cell migration, survival, inflammation, and angiogenesis as well as miR29c and miR150. Remarkably, the transfection of dAT-MSCs with nAT-MSC-derived MVs improved their migration ability in vitro and wound healing ability in a flap mouse model. These results demonstrate a promising opportunity to modify the function of dAT-MSCs for therapeutic stem cell application in diabetic patients.
authors.affiliation: Graduate School of Comprehensive Human Science, Laboratory of Regenerative Medicine and Stem Cell Biology, University of Tsukuba, Tsukuba 305-8575, Japan.
authors.forename: Nhu Thuy
authors.initials: NT
authors.lastname: Trinh
authors.affiliation: Graduate School of Comprehensive Human Science, Laboratory of Regenerative Medicine and Stem Cell Biology, University of Tsukuba, Tsukuba 305-8575, Japan.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Yamashita
authors.affiliation: Graduate School of Comprehensive Human Science, Laboratory of Regenerative Medicine and Stem Cell Biology, University of Tsukuba, Tsukuba 305-8575, Japan.
authors.forename: Tran Cam
authors.initials: TC
authors.lastname: Tu
authors.affiliation: Graduate School of Comprehensive Human Science, Laboratory of Regenerative Medicine and Stem Cell Biology, University of Tsukuba, Tsukuba 305-8575, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Kato
authors.affiliation: Laboratory of Molecular Pathophysiology, Faculty of Pharmacy, Takasaki University of Health and Welfare, Takasaki 370-0033, Japan.
authors.forename: Kinuko
authors.initials: K
authors.lastname: Ohneda
authors.affiliation: Graduate School of Comprehensive Human Science, Department of Cardiovascular Surgery, University of Tsukuba, Tsukuba 305-8575, Japan.
authors.forename: Fujio
authors.initials: F
authors.lastname: Sato
authors.affiliation: Graduate School of Comprehensive Human Science, Laboratory of Regenerative Medicine and Stem Cell Biology, University of Tsukuba, Tsukuba 305-8575, Japan. Electronic address: oohneda@md.tsukuba.ac.jp.
authors.forename: Osamu
authors.initials: O
authors.lastname: Ohneda
mesh_terms: D017667:Adipocytes / Q000166:cytology*; D000818:Animals; D002465:Cell Movement; D055252:Cell-Derived Microparticles / Q000473:pathology / Q000502:physiology / Q000637:transplantation*; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology*; D005260:Female; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000473:pathology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016896:Treatment Outcome; D014945:Wound Healing / Q000502:physiology*
keywords: Diabetes; Flap mouse model; Mesenchymal stem cells; Microvesicles; Wound healing