title: Microparticles from kidney-derived mesenchymal stem cells act as carriers of proangiogenic signals and contribute to recovery from acute kidney injury.
abstract: We recently demonstrated the use of in vitro expanded kidney-derived mesenchymal stem cells (KMSC) protected peritubular capillary endothelial cells in acute renal ischemia-reperfusion injury. Herein, we isolated and characterized microparticles (MPs) from KMSC. We investigated their in vitro biologic effects on human endothelial cells and in vivo renoprotective effects in acute ischemia-reperfusion renal injury. MPs were isolated from the supernatants of KMSC cultured in anoxic conditions in serum-deprived media for 24 hours. KMSC-derived MPs demonstrated the presence of several adhesion molecules normally expressed on KMSC membranes, such as CD29, CD44, CD73, α4, 5, and 6 integrins. Quantitative real time PCR confirmed the presence of 3 splicing variants of VEGF-A (120, 164, 188), bFGF and IGF-1 in isolated MPs. MPs labeled with PKH26 red fluorescence dye were incorporated by cultured human umbilical vein endothelial cells (HUVEC) via surface molecules such as CD44, CD29, and α4, 5, and 6 integrins. MP dose dependently improved in vitro HUVEC proliferation and promoted endothelial tube formation on growth factor reduced Matrigel. Moreover, apoptosis of human microvascular endothelial cell was inhibited by MPs. Administration of KMSC-derived MPs into mice with acute renal ischemia was followed by selective engraftment in ischemic kidneys and significant improvement in renal function. This was achieved by improving proliferation, of peritubular capillary endothelial cell and amelioration of peritubular microvascular rarefaction. Our results support the hypothesis that KMSC-derived MPs may act as a source of proangiogenic signals and confer renoprotective effects in ischemic kidneys.
authors: Division of Nephrology, Department of Internal Medicine, Gangnam Severance Hospital, Seoul, Korea ; Severance Institute for Vascular and Metabolic Research, Yonsei University College of Medicine, Seoul, Korea.
authors: Hoon Young
authors: HY
authors: Choi
authors: Department of Internal Medicine, Kwandong University College of Medicine, Gangneung, Korea.
authors: Sung Jin
authors: SJ
authors: Moon
authors: Departments of Medicine, Pharmacology and Physiology, New York Medical College, Valhalla, New York, United States of America.
authors: Brian B
authors: BB
authors: Ratliff
authors: Division of Nephrology, Department of Internal Medicine, Gangnam Severance Hospital, Seoul, Korea.
authors: Sun Hee
authors: SH
authors: Ahn
authors: Division of Nephrology, Department of Internal Medicine, Gangnam Severance Hospital, Seoul, Korea.
authors: Ara
authors: A
authors: Jung
authors: Division of Nephrology, Department of Internal Medicine, Gangnam Severance Hospital, Seoul, Korea.
authors: Mirae
authors: M
authors: Lee
authors: Division of Nephrology, Department of Internal Medicine, Gangnam Severance Hospital, Seoul, Korea.
authors: Seol
authors: S
authors: Lee
authors: Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
authors: Beom Jin
authors: BJ
authors: Lim
authors: Division of Nephrology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors: Beom Seok
authors: BS
authors: Kim
authors: Departments of Medicine, Pharmacology and Physiology, New York Medical College, Valhalla, New York, United States of America.
authors: Matthew D
authors: MD
authors: Plotkin
authors: Division of Nephrology, Department of Internal Medicine, Gangnam Severance Hospital, Seoul, Korea.
authors: Sung Kyu
authors: SK
authors: Ha
authors: Division of Nephrology, Department of Internal Medicine, Gangnam Severance Hospital, Seoul, Korea ; Severance Institute for Vascular and Metabolic Research, Yonsei University College of Medicine, Seoul, Korea.
authors: Hyeong Cheon
authors: HC
authors: Park
mesh_terms: D058186:Acute Kidney Injury / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D001692:Biological Transport; D049109:Cell Proliferation; D055252:Cell-Derived Microparticles / Q000378:metabolism* / Q000648:ultrastructure; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism*; D020869:Gene Expression Profiling; D022761:Gene Transfer, Horizontal; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D018919:Neovascularization, Physiologic; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction