title: Use of mouse hematopoietic stem and progenitor cells to treat acute kidney injury.
abstract: New and effective treatment for acute kidney injury remains a challenge. Here, we induced mouse hematopoietic stem and progenitor cells (HSPC) to differentiate into cells that partially resemble a renal cell phenotype and tested their therapeutic potential. We sequentially treated HSPC with a combination of protein factors for 1 wk to generate a large number of cells that expressed renal developmentally regulated genes and protein. Cell fate conversion was associated with increased histone acetylation on promoters of renal-related genes. Further treatment of the cells with a histone deacetylase inhibitor improved the efficiency of cell conversion by sixfold. Treated cells formed tubular structures in three-dimensional cultures and were integrated into tubules of embryonic kidney organ cultures. When injected under the renal capsule, they integrated into renal tubules of postischemic kidneys and expressed the epithelial marker E-cadherin. No teratoma formation was detected 2 and 6 mo after cell injection, supporting the safety of using these cells. Furthermore, intravenous injection of the cells into mice with renal ischemic injury improved kidney function and morphology by increasing endogenous renal repair and decreasing tubular cell death. The cells produced biologically effective concentrations of renotrophic factors including VEGF, IGF-1, and HGF to stimulate epithelial proliferation and tubular repair. Our study indicates that hematopoietic stem and progenitor cells can be converted to a large number of renal-like cells within a short period for potential treatment of acute kidney injury.
authors.affiliation: Dept. of Pediatrics, Columbia Univ. College of Physicians and Surgeons, 630 West 168th St., New York, NY 10032, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Rachel
authors.initials: R
authors.lastname: Black
authors.forename: Zhendong
authors.initials: Z
authors.lastname: Ma
authors.forename: Qiwen
authors.initials: Q
authors.lastname: Yang
authors.forename: Andrew
authors.initials: A
authors.lastname: Wang
authors.forename: Fangming
authors.initials: F
authors.lastname: Lin
mesh_terms: D000107:Acetylation; D058186:Acute Kidney Injury / Q000628:therapy*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D017228:Hepatocyte Growth Factor / Q000097:blood / Q000494:pharmacology; D006657:Histones / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007684:Kidney Tubules / Q000166:cytology / Q000502:physiology*; D008297:Male; D051379:Mice; D061251:Primary Cell Culture; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D006657:Histones; D006877:Hydroxamic Acids; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; C012589:trichostatin A; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor; D007334:Insulin-Like Growth Factor I