Nestin(+) kidney resident mesenchymal stem cells for the treatment of acute kidney ischemia injury.
Renal resident mesenchymal stem cells (MSCs) are important regulators of kidney homeostasis, repair or regeneration. However, natural distribution and the starting population properties of these cells remain elusive because of the lack of specific markers. Here, we identified post-natal kidney derived Nestin(+) cells that fulfilled all of the criteria as a mesenchymal stem cell. These isolated Nestin(+) cells expressed the typical cell-surface marker of MSC, including Sca-1, CD44, CD106, NG2 and PDGFR-α. They were capable of self-renewal, possessed high clonogenic potential and extensive proliferation for more than 30 passages. Under appropriate differentiation conditions, these cells could differentiate into adipocytes, osteocytes, chondrocytes and podocytes. After intravenous injection into acute kidney injury mice, Nestin(+) cells contributed to functional improvement by significantly decreasing the peak level of serum creatinine and BUN, and reducing the damaged cell apoptosis. Furthermore, conditioned medium from Nestin(+) cells could protect against ischemic acute renal failure partially through paracrine factor VEGF. Taken together, our findings indicate that renal resident Nestin(+) MSCs can be derived, propagated, differentiated, and repair the acute kidney injury, which may shed new light on understanding MSCs biology and developing cell replacement therapies for kidney disease.
Cell-gene Therapy Translational Medicine Research Center, The Third Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, China; Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Mei Hua
MH
Jiang
Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, China.
Guilan
G
Li
Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, China; Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Junfeng
J
Liu
Laboratory of General Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Longshan
L
Liu
Department of Cardiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Bingyuan
B
Wu
Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, China.
Weijun
W
Huang
Department of Geriatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Wen
W
He
Department of Urology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Chunhua
C
Deng
Department of Laboratory Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Dong
D
Wang
Institute of Hypertension & Kidney Research, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Chunling
C
Li
Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, China.
Bruce T
BT
Lahn
Department of Nephrology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. Electronic address: ericshi412@sina.com.
Chenggang
C
Shi
Cell-gene Therapy Translational Medicine Research Center, The Third Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, China; Department of Biochemistry, Zhongshan Medical School, Sun Yat-sen University, Guangzhou, China. Electronic address: xiangp@mail.sysu.edu.cn.
Andy Peng
AP
Xiang
D058186:Acute Kidney Injury / Q000150:complications / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D002999:Clone Cells; D003114:Colony-Forming Units Assay; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007511:Ischemia / Q000150:complications / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D007677:Kidney Function Tests; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D039902:Multipotent Stem Cells / Q000166:cytology / Q000187:drug effects; D064231:Nestin / Q000378:metabolism*; D020011:Protective Agents / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D017077:Culture Media, Conditioned; D064231:Nestin; D020011:Protective Agents; D042461:Vascular Endothelial Growth Factor A; D049452:Green Fluorescent Proteins
Acute kidney injury; MSCs; Nestin; Paracrine; VEGF