Transplantation of human fetal mesenchymal stem cells improves glomerulopathy in a collagen type I(alpha)2-deficient mouse

Guillot, P, Cook, H, Pusey, C, Fisk, N, Harten, S, Moss, J, Shore, I and Bou-Gharios, G (2008) Transplantation of human fetal mesenchymal stem cells improves glomerulopathy in a collagen type I(alpha)2-deficient mouse. The Journal of Pathology, 214 5: 627-636.


Author Guillot, P
Cook, H
Pusey, C
Fisk, N
Harten, S
Moss, J
Shore, I
Bou-Gharios, G
Title Transplantation of human fetal mesenchymal stem cells improves glomerulopathy in a collagen type I(alpha)2-deficient mouse
Formatted title Transplantation of human fetal mesenchymal stem cells improves glomerulopathy in a collagen type Iα2-deficient mouse
Journal name The Journal of Pathology  (ERA 2012 Listed)    (ERA 2010 Rank A*)   Check publisher's open access policy
Publication date 2008-04
Sub-type Article
DOI 10.1002/path.2325
Volume number 214
Issue number 5
ISSN 0022-3417
Start page 627
End page 636
Total pages 10
Place of publication London, U.K.
Publisher John Wiley & Sons in association with the Pathological Society of Great Britain and Ireland.
Language eng
Subject 1103 Clinical Sciences
1108 Medical Microbiology
Formatted abstract Fetal mesenchymal stem cell (fetal MSC) therapy has potential to treat genetic diseases with early onset, including those affecting the kidney and urinary tract. A collagen type Iα2-deficient mouse has a deletion in the α2 chain of the procollagen type I gene, resulting in the synthesis of abnormal α1(I)3 homotrimers, which replace normal α1(I)2α2(I)1 heterotrimers and a glomerulopathy. We first confirmed that col1α2-deficient homozygous mice show abnormal collagen deposition in the glomeruli, which increases in frequency and severity with postnatal age. Intrauterine transplantation of human MSCs from first trimester fetal blood led postnatally to a reduction of abnormal homotrimeric collagen type I deposition in the glomeruli of 4-12 week-old col1α2-deficient mice. Using bioluminescence imaging, in situ hybridization and immunohistochemistry in transplanted col1α2-deficient mice, we showed that the damaged kidneys preferentially recruited donor cells in glomeruli, around mesangial cells. Real-time RT-PCR demonstrated that this effect was seen at an engraftment level of 1% of total cells in the kidney, albeit higher in glomeruli. We conclude that intrauterine transplantation of human fetal MSCs improves renal glomerulopathy in a collagen type I-deficient mouse model. These data support the feasibility of prenatal treatment for hereditary renal diseases.
Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Keyword Collagen type I
Fetal stem cells
Glomerulopathy
Intrauterine transplantation
Kidney
Mesenchymal stem cells
Mouse model
Q-Index Code C1

 
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