Transplantation of human hematopoietic stem cells into ischemic and growing kidneys suggests a role in vasculogenesis but not tubulogenesis.
Transplantation of murine bone marrow-derived stem cells has been reported recently to promote regeneration of the injured kidney. We investigated the potential of human adult CD34(+) progenitor cells to undergo renal differentiation once xenotransplanted into ischemic and developing kidneys. Immunostaining with human-specific antibodies for tubular cells (broad-spectrum cytokeratin), endothelial cells (CD31, PECAM), stromal cells (vimentin), and hematopoietic cells (pan-leukocyte CD45) demonstrated that although kidney ischemia enhanced engraftment of human cells, they were mostly hematopoietic cells (CD45(+)) residing in the interstitial spaces. Few other engrafted cells demonstrated an endothelial phenotype (human CD31(+)in morphologically appearing peritubular capillaries), but no evidence of tubular or stromal cells of human origin was found. Upregulation of SDF1 and HIF1 transcript levels in the ischemic kidneys might explain the diffuse engraftment of CD45(+)cells following injury. Similarly, when embryonic kidneys rudiments were co-transplanted with human CD34(+)cells in mice, we found both human CD45(+)and CD31(+)cells in the periphery of the developing renal grafts, whereas parenchymal elements failed to stain. In addition, human CD34(+)cells had no effect on kidney growth and differentiation. This first demonstration of human CD34(+)stem cell transplantation into injured and developing kidneys indicates that these cells do not readily acquire a tubular phenotype and are restricted mainly to hematopoietic and, to a lesser extent, to endothelial lineages. Efforts should be made to identify additional stem cell sources applicable for kidney growth and regeneration.
Dekel
Benjamin
B
Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Shezen
Elias
E
Even-Tov-Friedman
Smadar
S
Katchman
Helena
H
Margalit
Raanan
R
Nagler
Arnon
A
Reisner
Yair
Y
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D002454:Cell Differentiation; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology*; D005786:Gene Expression Regulation; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007511:Ischemia; D007668:Kidney / Q000098:blood supply* / Q000166:cytology / Q000196:embryology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D006899:Mixed Function Oxygenases; D018919:Neovascularization, Physiologic / Q000502:physiology*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D013552:Swine; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014183:Transplantation, Heterologous; D015854:Up-Regulation
D018952:Antigens, CD34; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; D006899:Mixed Function Oxygenases; C439790:HIF1AN protein, human