Biomimetic reconstruction of the hematopoietic stem cell niche for in vitro amplification of human hematopoietic stem cells.
Hematopoietic stem cell transplantation is successfully applied since the late 1950s; however, its efficacy still needs to be increased. A promising strategy is to transplant high numbers of pluripotent hematopoietic stem cells (HSCs). Therefore, an improved ex vivo culture system that supports prol...
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doaj-38cfdc3754a34aa0bc1c670d24a286242021-03-03T21:51:36ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01156e023463810.1371/journal.pone.0234638Biomimetic reconstruction of the hematopoietic stem cell niche for in vitro amplification of human hematopoietic stem cells.L Marx-BlümelC MarxF WeiseJ FreyB PernerG SchlingloffN LindigJ HamplJ SonnemannD BrauerA VoigtS SinghB BeckUte-Maria JägerZ Q WangJ F BeckA SchoberHematopoietic stem cell transplantation is successfully applied since the late 1950s; however, its efficacy still needs to be increased. A promising strategy is to transplant high numbers of pluripotent hematopoietic stem cells (HSCs). Therefore, an improved ex vivo culture system that supports proliferation and maintains HSC pluripotency would override possible limitations in cell numbers gained from donors. To model the natural HSC niche in vitro, we optimized the HSC medium composition with a panel of cytokines and valproic acid and used an artificial 3D bone marrow-like scaffold made of polydimethylsiloxane (PDMS). This 3D scaffold offered a suitable platform to amplify human HSCs in vitro and, simultaneously, to support their viability, multipotency and ability for self-renewal. Silicon oxide-covering of PDMS structures further improved amplification of CD34+ cells, although the conservation of naïve HSCs was better on non-covered 3D PDMS. Finally, we found that HSC cultivated on non-covered 3D PDMS generated most pluripotent colonies within colony forming unit assays. In conclusion, by combining biological and biotechnological approaches, we optimized in vitro HSCs culture conditions, resulting in improved amplification, multipotency maintenance and vitality of HSCs.https://doi.org/10.1371/journal.pone.0234638 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
L Marx-Blümel C Marx F Weise J Frey B Perner G Schlingloff N Lindig J Hampl J Sonnemann D Brauer A Voigt S Singh B Beck Ute-Maria Jäger Z Q Wang J F Beck A Schober |
spellingShingle |
L Marx-Blümel C Marx F Weise J Frey B Perner G Schlingloff N Lindig J Hampl J Sonnemann D Brauer A Voigt S Singh B Beck Ute-Maria Jäger Z Q Wang J F Beck A Schober Biomimetic reconstruction of the hematopoietic stem cell niche for in vitro amplification of human hematopoietic stem cells. PLoS ONE |
author_facet |
L Marx-Blümel C Marx F Weise J Frey B Perner G Schlingloff N Lindig J Hampl J Sonnemann D Brauer A Voigt S Singh B Beck Ute-Maria Jäger Z Q Wang J F Beck A Schober |
author_sort |
L Marx-Blümel |
title |
Biomimetic reconstruction of the hematopoietic stem cell niche for in vitro amplification of human hematopoietic stem cells. |
title_short |
Biomimetic reconstruction of the hematopoietic stem cell niche for in vitro amplification of human hematopoietic stem cells. |
title_full |
Biomimetic reconstruction of the hematopoietic stem cell niche for in vitro amplification of human hematopoietic stem cells. |
title_fullStr |
Biomimetic reconstruction of the hematopoietic stem cell niche for in vitro amplification of human hematopoietic stem cells. |
title_full_unstemmed |
Biomimetic reconstruction of the hematopoietic stem cell niche for in vitro amplification of human hematopoietic stem cells. |
title_sort |
biomimetic reconstruction of the hematopoietic stem cell niche for in vitro amplification of human hematopoietic stem cells. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2020-01-01 |
description |
Hematopoietic stem cell transplantation is successfully applied since the late 1950s; however, its efficacy still needs to be increased. A promising strategy is to transplant high numbers of pluripotent hematopoietic stem cells (HSCs). Therefore, an improved ex vivo culture system that supports proliferation and maintains HSC pluripotency would override possible limitations in cell numbers gained from donors. To model the natural HSC niche in vitro, we optimized the HSC medium composition with a panel of cytokines and valproic acid and used an artificial 3D bone marrow-like scaffold made of polydimethylsiloxane (PDMS). This 3D scaffold offered a suitable platform to amplify human HSCs in vitro and, simultaneously, to support their viability, multipotency and ability for self-renewal. Silicon oxide-covering of PDMS structures further improved amplification of CD34+ cells, although the conservation of naïve HSCs was better on non-covered 3D PDMS. Finally, we found that HSC cultivated on non-covered 3D PDMS generated most pluripotent colonies within colony forming unit assays. In conclusion, by combining biological and biotechnological approaches, we optimized in vitro HSCs culture conditions, resulting in improved amplification, multipotency maintenance and vitality of HSCs. |
url |
https://doi.org/10.1371/journal.pone.0234638 |
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