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TISSUE-SPECIFIC STEM CELLS

Widespread Nonhematopoietic Tissue Distribution by Transplanted Human Progenitor Cells with High Aldehyde Dehydrogenase Activity

^aHematopoietic Development and Malignancy Group, Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA;
^bDepartment of Pathology and Laboratory Medicine, St. Louis University School of Medicine, Cardinal Glennon Hospital Cord Blood Banking Facility, St. Louis, Missouri, USA

Key Words. Transplantation • NOD/SCID model • Umbilical cord blood • Aldehyde dehydrogenase • CD133

Correspondence: David A. Hess, Ph.D., Krembil Centre for Stem Cell Biology, Robarts Research Institute, Room E4-18, 100 Perth Drive, London, Ontario N6A 5K8, Canada. Telephone: 519-663-4777, ext. 34152; Fax: 519-663-3789; e-mail: dhess{at}robarts.ca

Received June 1, 2007; accepted for publication November 19, 2007.
First published online in STEM CELLS EXPRESS   November 29, 2007.



Transplanted adult progenitor cells distribute to peripheral organs and can promote endogenous cellular repair in damaged tissues. However, development of cell-based regenerative therapies has been hindered by the lack of preclinical models to efficiently assess multiple organ distribution and difficulty defining human cells with regenerative function. After transplantation into β-glucuronidase (GUSB)-deficient NOD/SCID/mucopolysaccharidosis type VII mice, we characterized the distribution of lineage-depleted human umbilical cord blood-derived cells purified by selection using high aldehyde dehydrogenase (ALDH) activity with CD133 coexpression. ALDH^hi or ALDH^hiCD133⁺ cells produced robust hematopoietic reconstitution and variable levels of tissue distribution in multiple organs. GUSB⁺ donor cells that coexpressed human leukocyte antigen (HLA-A,B,C) and hematopoietic (CD45⁺) cell surface markers were the primary cell phenotype found adjacent to the vascular beds of several tissues, including islet and ductal regions of mouse pancreata. In contrast, variable phenotypes were detected in the chimeric liver, with HLA⁺/CD45⁺ cells demonstrating robust GUSB expression adjacent to blood vessels and CD45^–/HLA^– cells with diluted GUSB expression predominant in the liver parenchyma. However, true nonhematopoietic human (HLA⁺/CD45^–) cells were rarely detected in other peripheral tissues, suggesting that these GUSB⁺/HLA^–/CD45^– cells in the liver were a result of downregulated human surface marker expression in vivo, not widespread seeding of nonhematopoietic cells. However, relying solely on continued expression of cell surface markers, as used in traditional xenotransplantation models, may underestimate true tissue distribution. ALDH-expressing progenitor cells demonstrated widespread and tissue-specific distribution of variable cellular phenotypes, indicating that these adult progenitor cells should be explored in transplantation models of tissue damage.

Disclosure of potential conflicts of interest is found at the end of this article.