Engraftment Outcomes after HPC Co-Culture with Mesenchymal Stromal Cells and Osteoblasts
Haematopoietic stem cell (HSC) transplantation is an established cell-based therapy for a number of haematological diseases. To enhance this therapy, there is considerable interest in expanding HSCs in artificial niches prior to transplantation. This study compared murine HSC expansion supported thr...
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doaj-2138aade006244cb959ae695c9557ae12020-11-24T23:09:42ZengMDPI AGJournal of Clinical Medicine2077-03832013-09-012311513510.3390/jcm2030115Engraftment Outcomes after HPC Co-Culture with Mesenchymal Stromal Cells and OsteoblastsMatthew M. CookMichael R. DoranKatarina KollarValerie BarbierIngrid G. WinklerJean-Pierre LevesqueGary BrookeKerry AtkinsonHaematopoietic stem cell (HSC) transplantation is an established cell-based therapy for a number of haematological diseases. To enhance this therapy, there is considerable interest in expanding HSCs in artificial niches prior to transplantation. This study compared murine HSC expansion supported through co-culture on monolayers of either undifferentiated mesenchymal stromal cells (MSCs) or osteoblasts. Sorted Lineage− Sca-1+ c-kit+ (LSK) haematopoietic stem/progenitor cells (HPC) demonstrated proliferative capacity on both stromal monolayers with the greatest expansion of LSK shown in cultures supported by osteoblast monolayers. After transplantation, both types of bulk-expanded cultures were capable of engrafting and repopulating lethally irradiated primary and secondary murine recipients. LSKs co-cultured on MSCs showed comparable, but not superior, reconstitution ability to that of freshly isolated LSKs. Surprisingly, however, osteoblast co-cultured LSKs showed significantly poorer haematopoietic reconstitution compared to LSKs co-cultured on MSCs, likely due to a delay in short-term reconstitution. We demonstrated that stromal monolayers can be used to maintain, but not expand, functional HSCs without a need for additional haematopoietic growth factors. We also demonstrated that despite apparently superior in vitro performance, co-injection of bulk cultures of osteoblasts and LSKs in vivo was detrimental to recipient survival and should be avoided in translation to clinical practice.http://www.mdpi.com/2077-0383/2/3/115haematopoietic stem cellsmesenchymal stromal cellsosteoblastsex vivo expansionhaematopoietic reconstitution |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Matthew M. Cook Michael R. Doran Katarina Kollar Valerie Barbier Ingrid G. Winkler Jean-Pierre Levesque Gary Brooke Kerry Atkinson |
spellingShingle |
Matthew M. Cook Michael R. Doran Katarina Kollar Valerie Barbier Ingrid G. Winkler Jean-Pierre Levesque Gary Brooke Kerry Atkinson Engraftment Outcomes after HPC Co-Culture with Mesenchymal Stromal Cells and Osteoblasts Journal of Clinical Medicine haematopoietic stem cells mesenchymal stromal cells osteoblasts ex vivo expansion haematopoietic reconstitution |
author_facet |
Matthew M. Cook Michael R. Doran Katarina Kollar Valerie Barbier Ingrid G. Winkler Jean-Pierre Levesque Gary Brooke Kerry Atkinson |
author_sort |
Matthew M. Cook |
title |
Engraftment Outcomes after HPC Co-Culture with Mesenchymal Stromal Cells and Osteoblasts |
title_short |
Engraftment Outcomes after HPC Co-Culture with Mesenchymal Stromal Cells and Osteoblasts |
title_full |
Engraftment Outcomes after HPC Co-Culture with Mesenchymal Stromal Cells and Osteoblasts |
title_fullStr |
Engraftment Outcomes after HPC Co-Culture with Mesenchymal Stromal Cells and Osteoblasts |
title_full_unstemmed |
Engraftment Outcomes after HPC Co-Culture with Mesenchymal Stromal Cells and Osteoblasts |
title_sort |
engraftment outcomes after hpc co-culture with mesenchymal stromal cells and osteoblasts |
publisher |
MDPI AG |
series |
Journal of Clinical Medicine |
issn |
2077-0383 |
publishDate |
2013-09-01 |
description |
Haematopoietic stem cell (HSC) transplantation is an established cell-based therapy for a number of haematological diseases. To enhance this therapy, there is considerable interest in expanding HSCs in artificial niches prior to transplantation. This study compared murine HSC expansion supported through co-culture on monolayers of either undifferentiated mesenchymal stromal cells (MSCs) or osteoblasts. Sorted Lineage− Sca-1+ c-kit+ (LSK) haematopoietic stem/progenitor cells (HPC) demonstrated proliferative capacity on both stromal monolayers with the greatest expansion of LSK shown in cultures supported by osteoblast monolayers. After transplantation, both types of bulk-expanded cultures were capable of engrafting and repopulating lethally irradiated primary and secondary murine recipients. LSKs co-cultured on MSCs showed comparable, but not superior, reconstitution ability to that of freshly isolated LSKs. Surprisingly, however, osteoblast co-cultured LSKs showed significantly poorer haematopoietic reconstitution compared to LSKs co-cultured on MSCs, likely due to a delay in short-term reconstitution. We demonstrated that stromal monolayers can be used to maintain, but not expand, functional HSCs without a need for additional haematopoietic growth factors. We also demonstrated that despite apparently superior in vitro performance, co-injection of bulk cultures of osteoblasts and LSKs in vivo was detrimental to recipient survival and should be avoided in translation to clinical practice. |
topic |
haematopoietic stem cells mesenchymal stromal cells osteoblasts ex vivo expansion haematopoietic reconstitution |
url |
http://www.mdpi.com/2077-0383/2/3/115 |
work_keys_str_mv |
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