Cargando…

Transformation of Human Mesenchymal Cells and Skin Fibroblasts into Hematopoietic Cells

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....

Descripción completa

Detalles Bibliográficos
Autores principales: Harris, David M., Hazan-Haley, Inbal, Coombes, Kevin, Bueso-Ramos, Carlos, Liu, Jie, Liu, Zhiming, Li, Ping, Ravoori, Murali, Abruzzo, Lynne, Han, Lin, Singh, Sheela, Sun, Michael, Kundra, Vikas, Kurzrock, Razelle, Estrov, Zeev
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3120836/
https://www.ncbi.nlm.nih.gov/pubmed/21731684
http://dx.doi.org/10.1371/journal.pone.0021250
_version_ 1782206767643492352
author Harris, David M.
Hazan-Haley, Inbal
Coombes, Kevin
Bueso-Ramos, Carlos
Liu, Jie
Liu, Zhiming
Li, Ping
Ravoori, Murali
Abruzzo, Lynne
Han, Lin
Singh, Sheela
Sun, Michael
Kundra, Vikas
Kurzrock, Razelle
Estrov, Zeev
author_facet Harris, David M.
Hazan-Haley, Inbal
Coombes, Kevin
Bueso-Ramos, Carlos
Liu, Jie
Liu, Zhiming
Li, Ping
Ravoori, Murali
Abruzzo, Lynne
Han, Lin
Singh, Sheela
Sun, Michael
Kundra, Vikas
Kurzrock, Razelle
Estrov, Zeev
author_sort Harris, David M.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-3120836
institution National Center for Biotechnology Information
language English
publishDate 2011
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-31208362011-06-30 Transformation of Human Mesenchymal Cells and Skin Fibroblasts into Hematopoietic Cells Harris, David M. Hazan-Haley, Inbal Coombes, Kevin Bueso-Ramos, Carlos Liu, Jie Liu, Zhiming Li, Ping Ravoori, Murali Abruzzo, Lynne Han, Lin Singh, Sheela Sun, Michael Kundra, Vikas Kurzrock, Razelle Estrov, Zeev PLoS One Research Article 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. Public Library of Science 2011-06-22 /pmc/articles/PMC3120836/ /pubmed/21731684 http://dx.doi.org/10.1371/journal.pone.0021250 Text en Harris et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Harris, David M.
Hazan-Haley, Inbal
Coombes, Kevin
Bueso-Ramos, Carlos
Liu, Jie
Liu, Zhiming
Li, Ping
Ravoori, Murali
Abruzzo, Lynne
Han, Lin
Singh, Sheela
Sun, Michael
Kundra, Vikas
Kurzrock, Razelle
Estrov, Zeev
Transformation of Human Mesenchymal Cells and Skin Fibroblasts into Hematopoietic Cells
title Transformation of Human Mesenchymal Cells and Skin Fibroblasts into Hematopoietic Cells
title_full Transformation of Human Mesenchymal Cells and Skin Fibroblasts into Hematopoietic Cells
title_fullStr Transformation of Human Mesenchymal Cells and Skin Fibroblasts into Hematopoietic Cells
title_full_unstemmed Transformation of Human Mesenchymal Cells and Skin Fibroblasts into Hematopoietic Cells
title_short Transformation of Human Mesenchymal Cells and Skin Fibroblasts into Hematopoietic Cells
title_sort transformation of human mesenchymal cells and skin fibroblasts into hematopoietic cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3120836/
https://www.ncbi.nlm.nih.gov/pubmed/21731684
http://dx.doi.org/10.1371/journal.pone.0021250
work_keys_str_mv AT harrisdavidm transformationofhumanmesenchymalcellsandskinfibroblastsintohematopoieticcells
AT hazanhaleyinbal transformationofhumanmesenchymalcellsandskinfibroblastsintohematopoieticcells
AT coombeskevin transformationofhumanmesenchymalcellsandskinfibroblastsintohematopoieticcells
AT buesoramoscarlos transformationofhumanmesenchymalcellsandskinfibroblastsintohematopoieticcells
AT liujie transformationofhumanmesenchymalcellsandskinfibroblastsintohematopoieticcells
AT liuzhiming transformationofhumanmesenchymalcellsandskinfibroblastsintohematopoieticcells
AT liping transformationofhumanmesenchymalcellsandskinfibroblastsintohematopoieticcells
AT ravoorimurali transformationofhumanmesenchymalcellsandskinfibroblastsintohematopoieticcells
AT abruzzolynne transformationofhumanmesenchymalcellsandskinfibroblastsintohematopoieticcells
AT hanlin transformationofhumanmesenchymalcellsandskinfibroblastsintohematopoieticcells
AT singhsheela transformationofhumanmesenchymalcellsandskinfibroblastsintohematopoieticcells
AT sunmichael transformationofhumanmesenchymalcellsandskinfibroblastsintohematopoieticcells
AT kundravikas transformationofhumanmesenchymalcellsandskinfibroblastsintohematopoieticcells
AT kurzrockrazelle transformationofhumanmesenchymalcellsandskinfibroblastsintohematopoieticcells
AT estrovzeev transformationofhumanmesenchymalcellsandskinfibroblastsintohematopoieticcells