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

Authors

  • David A. Hess Ph.D.,

    Corresponding author
    1. Hematopoietic Development and Malignancy Group, Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA
    • 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
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  • Timothy P. Craft,

    1. Hematopoietic Development and Malignancy Group, Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA
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  • Louisa Wirthlin,

    1. Hematopoietic Development and Malignancy Group, Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA
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  • Sarah Hohm,

    1. Hematopoietic Development and Malignancy Group, Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA
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  • Ping Zhou,

    1. Hematopoietic Development and Malignancy Group, Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA
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  • William C. Eades,

    1. Hematopoietic Development and Malignancy Group, Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA
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  • Michael H. Creer,

    1. Department of Pathology and Laboratory Medicine, St. Louis University School of Medicine, Cardinal Glennon Hospital Cord Blood Banking Facility, St. Louis, Missouri, USA
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  • Mark S. Sands,

    1. Hematopoietic Development and Malignancy Group, Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA
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  • Jan A. Nolta

    1. Hematopoietic Development and Malignancy Group, Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA
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Abstract

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. ALDHhi or ALDHhiCD133+ 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.

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