Expansion on stromal cells preserves the undifferentiated state of human hematopoietic stem cells despite compromised reconstitution ability.
Lack of HLA-matched hematopoietic stem cells (HSC) limits the number of patients with life-threatening blood disorders that can be treated by HSC transplantation. So far, insufficient understanding of the regulatory mechanisms governing human HSC has precluded the development of effective protocols...
Guardado en:
| Autores principales: | , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2013
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/0b8c4615dcdf4df7995130c53d242d9c |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:0b8c4615dcdf4df7995130c53d242d9c |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:0b8c4615dcdf4df7995130c53d242d9c2021-11-18T08:01:14ZExpansion on stromal cells preserves the undifferentiated state of human hematopoietic stem cells despite compromised reconstitution ability.1932-620310.1371/journal.pone.0053912https://doaj.org/article/0b8c4615dcdf4df7995130c53d242d9c2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23342037/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Lack of HLA-matched hematopoietic stem cells (HSC) limits the number of patients with life-threatening blood disorders that can be treated by HSC transplantation. So far, insufficient understanding of the regulatory mechanisms governing human HSC has precluded the development of effective protocols for culturing HSC for therapeutic use and molecular studies. We defined a culture system using OP9M2 mesenchymal stem cell (MSC) stroma that protects human hematopoietic stem/progenitor cells (HSPC) from differentiation and apoptosis. In addition, it facilitates a dramatic expansion of multipotent progenitors that retain the immunophenotype (CD34+CD38-CD90+) characteristic of human HSPC and proliferative potential over several weeks in culture. In contrast, transplantable HSC could be maintained, but not significantly expanded, during 2-week culture. Temporal analysis of the transcriptome of the ex vivo expanded CD34+CD38-CD90+ cells documented remarkable stability of most transcriptional regulators known to govern the undifferentiated HSC state. Nevertheless, it revealed dynamic fluctuations in transcriptional programs that associate with HSC behavior and may compromise HSC function, such as dysregulation of PBX1 regulated genetic networks. This culture system serves now as a platform for modeling human multilineage hematopoietic stem/progenitor cell hierarchy and studying the complex regulation of HSC identity and function required for successful ex vivo expansion of transplantable HSC.Mattias MagnussonMaria I SierraRajkumar SasidharanSacha L PrashadMelissa RomeroPamela SaarikoskiBen Van HandelAndy HuangXinmin LiHanna K A MikkolaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e53912 (2013) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Mattias Magnusson Maria I Sierra Rajkumar Sasidharan Sacha L Prashad Melissa Romero Pamela Saarikoski Ben Van Handel Andy Huang Xinmin Li Hanna K A Mikkola Expansion on stromal cells preserves the undifferentiated state of human hematopoietic stem cells despite compromised reconstitution ability. |
| description |
Lack of HLA-matched hematopoietic stem cells (HSC) limits the number of patients with life-threatening blood disorders that can be treated by HSC transplantation. So far, insufficient understanding of the regulatory mechanisms governing human HSC has precluded the development of effective protocols for culturing HSC for therapeutic use and molecular studies. We defined a culture system using OP9M2 mesenchymal stem cell (MSC) stroma that protects human hematopoietic stem/progenitor cells (HSPC) from differentiation and apoptosis. In addition, it facilitates a dramatic expansion of multipotent progenitors that retain the immunophenotype (CD34+CD38-CD90+) characteristic of human HSPC and proliferative potential over several weeks in culture. In contrast, transplantable HSC could be maintained, but not significantly expanded, during 2-week culture. Temporal analysis of the transcriptome of the ex vivo expanded CD34+CD38-CD90+ cells documented remarkable stability of most transcriptional regulators known to govern the undifferentiated HSC state. Nevertheless, it revealed dynamic fluctuations in transcriptional programs that associate with HSC behavior and may compromise HSC function, such as dysregulation of PBX1 regulated genetic networks. This culture system serves now as a platform for modeling human multilineage hematopoietic stem/progenitor cell hierarchy and studying the complex regulation of HSC identity and function required for successful ex vivo expansion of transplantable HSC. |
| format |
article |
| author |
Mattias Magnusson Maria I Sierra Rajkumar Sasidharan Sacha L Prashad Melissa Romero Pamela Saarikoski Ben Van Handel Andy Huang Xinmin Li Hanna K A Mikkola |
| author_facet |
Mattias Magnusson Maria I Sierra Rajkumar Sasidharan Sacha L Prashad Melissa Romero Pamela Saarikoski Ben Van Handel Andy Huang Xinmin Li Hanna K A Mikkola |
| author_sort |
Mattias Magnusson |
| title |
Expansion on stromal cells preserves the undifferentiated state of human hematopoietic stem cells despite compromised reconstitution ability. |
| title_short |
Expansion on stromal cells preserves the undifferentiated state of human hematopoietic stem cells despite compromised reconstitution ability. |
| title_full |
Expansion on stromal cells preserves the undifferentiated state of human hematopoietic stem cells despite compromised reconstitution ability. |
| title_fullStr |
Expansion on stromal cells preserves the undifferentiated state of human hematopoietic stem cells despite compromised reconstitution ability. |
| title_full_unstemmed |
Expansion on stromal cells preserves the undifferentiated state of human hematopoietic stem cells despite compromised reconstitution ability. |
| title_sort |
expansion on stromal cells preserves the undifferentiated state of human hematopoietic stem cells despite compromised reconstitution ability. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/0b8c4615dcdf4df7995130c53d242d9c |
| work_keys_str_mv |
AT mattiasmagnusson expansiononstromalcellspreservestheundifferentiatedstateofhumanhematopoieticstemcellsdespitecompromisedreconstitutionability AT mariaisierra expansiononstromalcellspreservestheundifferentiatedstateofhumanhematopoieticstemcellsdespitecompromisedreconstitutionability AT rajkumarsasidharan expansiononstromalcellspreservestheundifferentiatedstateofhumanhematopoieticstemcellsdespitecompromisedreconstitutionability AT sachalprashad expansiononstromalcellspreservestheundifferentiatedstateofhumanhematopoieticstemcellsdespitecompromisedreconstitutionability AT melissaromero expansiononstromalcellspreservestheundifferentiatedstateofhumanhematopoieticstemcellsdespitecompromisedreconstitutionability AT pamelasaarikoski expansiononstromalcellspreservestheundifferentiatedstateofhumanhematopoieticstemcellsdespitecompromisedreconstitutionability AT benvanhandel expansiononstromalcellspreservestheundifferentiatedstateofhumanhematopoieticstemcellsdespitecompromisedreconstitutionability AT andyhuang expansiononstromalcellspreservestheundifferentiatedstateofhumanhematopoieticstemcellsdespitecompromisedreconstitutionability AT xinminli expansiononstromalcellspreservestheundifferentiatedstateofhumanhematopoieticstemcellsdespitecompromisedreconstitutionability AT hannakamikkola expansiononstromalcellspreservestheundifferentiatedstateofhumanhematopoieticstemcellsdespitecompromisedreconstitutionability |
| _version_ |
1718422586913718272 |