Comparison of multipotency and molecular profile of MSCs between CKD and healthy rats.
We previously showed that mesenchymal stem cells (MSCs) can differentiate into a functional miniature kidney, suggesting that MSCs may be a cell source for kidney regeneration. However, MSCs from long-term dialysis patients, which have been exposed to uremic toxin, can exhibit reduced viability. Therefore, the aim of this study was to examine the gene expression profiles and differentiation capabilities of bone marrow- and adipose-derived MSCs from chronic kidney disease (CKD) model rats. CKD was induced in rats by adenine feeding, and then MSCs were isolated from bone marrow (BMSCs) and adipose tissue (ASCs). After confirming MSC surface marker expression, comprehensive gene expression profiles were obtained by RT-PCR array. MSCs were differentiated into adipocytes, osteoblasts, and chondrocytes, and histological and/or functional assays were performed. Tgfb3 expression was up-regulated, while Bmp6, Gdf15, Mmp2, and Vegfa were down-regulated in CKD-ASCs compared with Control-ASCs. There were no significant differences in the gene expression of stemness markers, and the morphology of cells that underwent adipogenesis, osteogenesis, and chondrogenesis, or GPDH activity between CKD and control groups. Comparing BMSCs with ASCs, gene expression of Bglap, Bmp4, Igf1, Itgax, Pparg, Ptprc, and Tnf were up-regulated, while Col1a1, Mmp2, Sox9, and Vegfa were down-regulated in both CKD and control groups. Uremic toxin in CKD rats had a small effect on the gene expression and differentiation of MSCs. However, long-term exposure to uremic toxin and the differences in gene expression of MSCs derived from bone marrow or adipose tissue may affect renal regeneration.
Project Laboratory for Kidney Regeneration, Institute of DNA Medicine, The Jikei University School of Medicine, Tokyo, Japan.
Akifumi
A
Yamada
Takashi
T
Yokoo
Shinya
S
Yokote
Shuichiro
S
Yamanaka
Luna
L
Izuhara
Yuichi
Y
Katsuoka
Yohta
Y
Shimada
Akinori
A
Shukuya
Hirotaka James
HJ
Okano
Toya
T
Ohashi
Hiroyuki
H
Ida
D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D055418:Bone Morphogenetic Protein 6 / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015536:Down-Regulation; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D055436:Growth Differentiation Factor 15 / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000502:physiology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D012038:Regeneration / Q000235:genetics; D051436:Renal Insufficiency, Chronic / Q000473:pathology* / Q000503:physiopathology; D053782:Transforming Growth Factor beta3 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
C525818:Bmp6 protein, rat; D055418:Bone Morphogenetic Protein 6; C526142:Gdf15 protein, rat; D055436:Growth Differentiation Factor 15; D053782:Transforming Growth Factor beta3; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat