Kidney preservation by bone marrow cell transplantation in hereditary nephropathy.
The prospect of cell-based therapy for kidney disease remains controversial despite its immense promise. We had previously shown that transplanting bone marrow and hematopoietic stem cells could generate renal cells and lead to the preservation of kidney function in a mouse model for cystinosis (Ctns(-/-)) that develops chronic kidney injury, 4 months post transplantation. Here, we determined the long-term effects of bone marrow stem cell transplantation on the kidney disease of Ctns(-/-) mice 7 to 15 months post transplantation. Transfer of bone marrow stem cells expressing a functional Ctns gene provided long-term protection to the kidney. Effective therapy, however, depended on achieving a relatively high level of donor-derived blood cell engraftment of Ctns-expressing cells, which was directly linked to the quantity of these cells within the kidney. In contrast, kidney preservation was dependent neither on renal cystine content nor on the age of the mice at the time of transplant. Most of the bone marrow-derived cells within the kidney were interstitial and not epithelial, suggesting that the mechanism involved an indirect protection of the tubules. Thus, our model may help in developing strategies to enhance the potential success of cell-based therapy for kidney injury and in understanding some of the discrepancies currently existing in the field.
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA.
Brian A
BA
Yeagy
Frank
F
Harrison
Marie-Claire
MC
Gubler
James A
JA
Koziol
Daniel R
DR
Salomon
Stephanie
S
Cherqui
D000469:Alkaline Phosphatase / Q000097:blood; D026921:Amino Acid Transport Systems, Neutral / Q000172:deficiency / Q000235:genetics; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D002478:Cells, Cultured; D002908:Chronic Disease; D003404:Creatinine / Q000097:blood; D003545:Cysteine / Q000378:metabolism; D003554:Cystinosis / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation; D007668:Kidney / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D007674:Kidney Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D016014:Linear Models; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010710:Phosphates / Q000097:blood / Q000652:urine; D011507:Proteinuria / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D013997:Time Factors; D018183:Transplantation Chimera; D014508:Urea / Q000097:blood
D026921:Amino Acid Transport Systems, Neutral; D015415:Biomarkers; D010710:Phosphates; C534463:cystinosin protein, mouse; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D014508:Urea; D003404:Creatinine; D000469:Alkaline Phosphatase; D003545:Cysteine