Transplantation of human fetal mesenchymal stem cells improves glomerulopathy in a collagen type I alpha 2-deficient mouse.
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 I alpha 2-deficient mouse has a deletion in the alpha2 chain of the procollagen type I gene, resulting in the synthesis of abnormal alpha1(I)(3) homotrimers, which replace normal alpha 1(I)2 alpha 2(I)1 heterotrimers and a glomerulopathy. We first confirmed that col1 alpha 2-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 col1 alpha 2-deficient mice. Using bioluminescence imaging, in situ hybridization and immunohistochemistry in transplanted col1 alpha 2-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.
Guillot
P V
PV
Experimental Fetal Medicine Group, Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, London, UK. Pascale.Guillot@imperial.ac.uk
Cook
H T
HT
Pusey
C D
CD
Fisk
N M
NM
Harten
S
S
Moss
J
J
Shore
I
I
Bou-Gharios
G
G
D000818:Animals; D024042:Collagen Type I / Q000096:biosynthesis / Q000172:deficiency* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005315:Fetal Diseases / Q000628:therapy*; D053686:Fetal Stem Cells / Q000637:transplantation*; D046128:Fetal Therapies / Q000379:methods; D006085:Graft Survival; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D007678:Kidney Glomerulus / Q000378:metabolism / Q000648:ultrastructure*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D051379:Mice; D008854:Microscopy, Electron
D024042:Collagen Type I