Engraftment outcomes after HPC co-culture with mesenchymal stromal cells and osteoblasts
Cook, Matthew M., Doran, Michael R., Kollar, Katarina, Barbier, Valerie, Winkler, Ingrid G., Levesque, Jean-Pierre, Brooke, Gary, & Atkinson, Kerry (2013) Engraftment outcomes after HPC co-culture with mesenchymal stromal cells and osteoblasts. Journal of Clinical Medicine, 2(3), pp. 115-135.
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.
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|Item Type:||Journal Article|
|Keywords:||haematopoietic stem cells; mesenchymal stromal cells; osteoblasts; ex vivo expansion; haematopoietic reconstitution|
|Subjects:||Australian and New Zealand Standard Research Classification > ENGINEERING (090000) > BIOMEDICAL ENGINEERING (090300)|
|Divisions:||Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
|Copyright Owner:||Copyright 2013 by the authors; licensee MDPI, Basel, Switzerland|
|Copyright Statement:||This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).|
|Deposited On:||10 Mar 2014 22:57|
|Last Modified:||15 Mar 2014 01:54|
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