Transplantation of human CD34⁺CD133⁺ hematopoietic stem cells into ischemic and growing kidneys suggests role in vasculogenesis but not tubulogenesis

¹ Department of Immunology, Weizmann Institute of Science, Rehovot, Israel
² Division of Hematology, Sheba Medical Center, Tel Hashomer, Israel

^* To whom correspondence should be addressed. E-mail: yair.reisner{at}weizmann.ac.il.

	Abstract

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 while 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. Up-regulation of SDF-1 and HIF-1 transcript levels in the ischemic kidneys might explain the diffuse engraftment of CD45⁺ cells following injury. Similarly, when embryonic kidneys rudiments were cotransplanted with human CD34⁺ cells in mice, we found both human CD45⁺ and CD31⁺ cells in the periphery of the developing renal grafts, while 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 lineage. Efforts should be made to identify additional stem cell sources applicable for kidney growth and regeneration.

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