title: Transformation of human mesenchymal cells and skin fibroblasts into hematopoietic cells.
abstract: Patients with prolonged myelosuppression require frequent platelet and occasional granulocyte transfusions. Multi-donor transfusions induce alloimmunization, thereby increasing morbidity and mortality. Therefore, an autologous or HLA-matched allogeneic source of platelets and granulocytes is needed. To determine whether nonhematopoietic cells can be reprogrammed into hematopoietic cells, human mesenchymal stromal cells (MSCs) and skin fibroblasts were incubated with the demethylating agent 5-azacytidine (Aza) and the growth factors (GF) granulocyte-macrophage colony-stimulating factor and stem cell factor. This treatment transformed MSCs to round, non-adherent cells expressing T-, B-, myeloid-, or stem/progenitor-cell markers. The transformed cells engrafted as hematopoietic cells in bone marrow of immunodeficient mice. DNA methylation and mRNA array analysis suggested that Aza and GF treatment demethylated and activated HOXB genes. Indeed, transfection of MSCs or skin fibroblasts with HOXB4, HOXB5, and HOXB2 genes transformed them into hematopoietic cells. Further studies are needed to determine whether transformed MSCs or skin fibroblasts are suitable for therapy.
authors: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors: David M
authors: DM
authors: Harris
authors: Inbal
authors: I
authors: Hazan-Haley
authors: Kevin
authors: K
authors: Coombes
authors: Carlos
authors: C
authors: Bueso-Ramos
authors: Jie
authors: J
authors: Liu
authors: Zhiming
authors: Z
authors: Liu
authors: Ping
authors: P
authors: Li
authors: Murali
authors: M
authors: Ravoori
authors: Lynne
authors: L
authors: Abruzzo
authors: Lin
authors: L
authors: Han
authors: Sheela
authors: S
authors: Singh
authors: Michael
authors: M
authors: Sun
authors: Vikas
authors: V
authors: Kundra
authors: Razelle
authors: R
authors: Kurzrock
authors: Zeev
authors: Z
authors: Estrov
mesh_terms: D000818:Animals; D001374:Azacitidine / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D002460:Cell Line; D054338:Cell Transdifferentiation / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D016513:Mice, SCID; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000166:cytology*; D019089:Stem Cell Factor / Q000494:pharmacology; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014162:Transfection
chemical_list: D015415:Biomarkers; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D019089:Stem Cell Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D001374:Azacitidine