Intravenous cell therapy for acute renal failure with serum amyloid A protein-reprogrammed cells.
Serum amyloid A protein (SAA), a prominent component of the acute-phase response, is strongly expressed in developing and repairing kidneys and promotes tubulogenesis. Accordingly, we reprogrammed relatively undifferentiated NRK52E cells with the mouse SAA1.1 gene and transplanted SAA-positive and -negative cells into rats with acute renal failure. We found that SAA-positive cells accelerated renal recovery in three models of acute renal failure: gentamicin nephrotoxicity, cisplatin-mediated renal injury, and ischemia-reperfusion renal injury. The dramatic improvement of renal failure was demonstrable within 2 days, consistent with an early paracrine effect. However, abundant donor cells were also found integrated in the healing tubular architecture after 7 days. We conclude that infusions of SAA-positive cells promote renal recovery after acute renal failure and offer a potentially powerful and novel therapy of renal failure.
Kelly
Katherine J
KJ
Departments of Medicine, Indiana University, Indianapolis, USA.
Kluve-Beckerman
Barbara
B
Zhang
Jizhong
J
Dominguez
Jesus H
JH
D058186:Acute Kidney Injury / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D049109:Cell Proliferation; D017690:Cell Transplantation; D002945:Cisplatin; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D005838:Genotype; D005839:Gentamicins; D007668:Kidney / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D027362:Organic Anion Transport Protein 1 / Q000378:metabolism; D010641:Phenotype; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D000685:Serum Amyloid A Protein / Q000096:biosynthesis* / Q000235:genetics; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
D005839:Gentamicins; D027362:Organic Anion Transport Protein 1; D018809:Proliferating Cell Nuclear Antigen; C489995:Saa2 protein, mouse; D000685:Serum Amyloid A Protein; C421043:Slc22a6 protein, rat; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D002945:Cisplatin