Transformation of human mesenchymal cells and skin fibroblasts into hematopoietic cells. PLoS One 2011;6(6):e21250
Date
07/07/2011Pubmed ID
21731684Pubmed Central ID
PMC3120836DOI
10.1371/journal.pone.0021250Scopus ID
2-s2.0-79959469517 (requires institutional sign-in at Scopus site) 30 CitationsAbstract
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.
Author List
Harris DM, Hazan-Haley I, Coombes K, Bueso-Ramos C, Liu J, Liu Z, Li P, Ravoori M, Abruzzo L, Han L, Singh S, Sun M, Kundra V, Kurzrock R, Estrov ZAuthor
Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAzacitidine
Biomarkers
Bone Marrow Cells
Cell Line
Cell Transdifferentiation
DNA Methylation
Fibroblasts
Granulocyte-Macrophage Colony-Stimulating Factor
Hematopoiesis
Hematopoietic Stem Cells
Homeodomain Proteins
Humans
Intercellular Signaling Peptides and Proteins
Mesenchymal Stem Cell Transplantation
Mice
Mice, SCID
Oligonucleotide Array Sequence Analysis
RNA, Messenger
Skin
Stem Cell Factor
Stromal Cells
Transfection