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Microparticles from Kidney-Derived Mesenchymal Stem Cells Act as Carriers of Proangiogenic Signals and Contribute to Recovery from Acute Kidney Injury

Authors
 Hoon Young Choi  ;  Sung Jin Moon  ;  Brian B. Ratliff  ;  Sun Hee Ahn  ;  Ara Jung  ;  Mirae Lee  ;  Seol Lee  ;  Beom Jin Lim  ;  Beom Seok Kim  ;  Matthew D. Plotkin  ;  Sung Kyu Ha  ;  Hyeong Cheon Park  ;  Hoon Young Choi  ;  Sung Jin Moon  ;  Brian B. Ratliff  ;  Sun Hee Ahn  ;  Ara Jung  ;  Mirae Lee  ;  Seol Lee  ;  Beom Jin Lim  ;  Beom Seok Kim  ;  Matthew D. Plotkin  ;  Sung Kyu Ha  ;  Hyeong Cheon Park 
Citation
 PLOS ONE, Vol.9(2) : e87853, 2014 
Journal Title
 PLOS ONE 
Issue Date
2014
MeSH
Acute Kidney Injury/genetics ; Acute Kidney Injury/metabolism* ; Acute Kidney Injury/pathology ; Animals ; Apoptosis ; Biological Transport ; Cell Proliferation ; Cell-Derived Microparticles/metabolism* ; Cell-Derived Microparticles/ultrastructure ; Disease Models, Animal ; Endothelial Cells/metabolism* ; Gene Expression Profiling ; Gene Transfer, Horizontal ; Human Umbilical Vein Endothelial Cells ; Humans ; Male ; Mesenchymal Stromal Cells/metabolism* ; Mice ; Neovascularization, Physiologic ; Reperfusion Injury/genetics ; Reperfusion Injury/metabolism ; Reperfusion Injury/pathology ; Signal Transduction*
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.
Files in This Item:
T201400266.pdf Download
DOI
10.1371/journal.pone.0087853
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Beom Seok(김범석) ORCID logo https://orcid.org/0000-0002-5732-2583
Park, Hyeong Cheon(박형천) ORCID logo https://orcid.org/0000-0002-1550-0812
Lim, Beom Jin(임범진) ORCID logo https://orcid.org/0000-0003-2856-0133
Choi, Hoon Young(최훈영) ORCID logo https://orcid.org/0000-0002-4245-0339
Ha, Sung Kyu(하성규)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/98094
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