Inability of human induced pluripotent stem cell-hematopoietic derivatives to downregulate microRNAs in vivo reveals a block in xenograft hematopoietic regeneration
Autor: | Ruth M. Risueño, Seok-Ho Hong, Jung Bok Lee, Mickie Bhatia, Eleftherios Sachlos, Jong-Hee Lee, Eva Szabo |
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Rok vydání: | 2011 |
Předmět: |
Induced Pluripotent Stem Cells
Transplantation Heterologous Down-Regulation Stem cell factor Bone Marrow Cells Mice SCID Biology Mice Bone Marrow Mice Inbred NOD medicine Animals Humans Regeneration Induced pluripotent stem cell Cells Cultured Embryonic Stem Cells Stem cell transplantation for articular cartilage repair Cell Proliferation Gene Expression Profiling Hematopoietic Stem Cell Transplantation Cell Differentiation Cell Biology Hematopoietic Stem Cells Embryonic stem cell Antigens Differentiation Cell biology Hematopoiesis Endothelial stem cell MicroRNAs medicine.anatomical_structure Immunology Molecular Medicine Bone marrow Stem cell Developmental Biology Adult stem cell |
Zdroj: | Stem cells (Dayton, Ohio). 30(2) |
ISSN: | 1549-4918 |
Popis: | Hematopoietic stem cells (HSCs) can regenerate the entire hematopoietic system in vivo, providing the most relevant criteria to measure candidate HSCs derived from human embryonic stem cell (hESC) or induced pluripotent stem cell (hiPSC) sources. Here we show that, unlike primitive hematopoietic cells derived from hESCs, phenotypically identical cells derived from hiPSC are more permissive to graft the bone marrow of xenotransplantation recipients. Despite establishment of bone marrow graft, hiPSC-derived cells fail to demonstrate hematopoietic differentiation in vivo. However, once removed from recipient bone marrow, hiPSC-derived grafts were capable of in vitro multilineage hematopoietic differentiation, indicating that xenograft imparts a restriction to in vivo hematopoietic progression. This failure to regenerate multilineage hematopoiesis in vivo was attributed to the inability to downregulate key microRNAs involved in hematopoiesis. Based on these analyses, our study indicates that hiPSCs provide a beneficial source of pluripotent stem cell-derived hematopoietic cells for transplantation compared with hESCs. Since use of the human–mouse xenograft models prevents detection of putative hiPSC-derived HSCs, we suggest that new preclinical models should be explored to fully evaluate cells generated from hiPSC sources. Disclosure of potential conflicts of interest is found at the end of this article. |
Databáze: | OpenAIRE |
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