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 and Atkinson, Kerry (2013) Engraftment outcomes after HPC co-culture with mesenchymal stromal cells and osteoblasts. Journal of Clinical Medicine, 2 3: 115-135. doi:10.3390/jcm2030115

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Author Cook, Matthew M.
Doran, Michael R.
Kollar, Katarina
Barbier, Valerie
Winkler, Ingrid G.
Levesque, Jean-Pierre
Brooke, Gary
Atkinson, Kerry
Title Engraftment outcomes after HPC co-culture with mesenchymal stromal cells and osteoblasts
Journal name Journal of Clinical Medicine   Check publisher's open access policy
ISSN 2077-0383
Publication date 2013-09-23
Sub-type Article (original research)
DOI 10.3390/jcm2030115
Open Access Status DOI
Volume 2
Issue 3
Start page 115
End page 135
Total pages 21
Place of publication Basel, Switzerland
Publisher M D P I
Collection year 2014
Language eng
Formatted abstract
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.
Keyword Haematopoietic stem cells
Mesenchymal stromal cells
Ex vivo expansion
Haematopoietic reconstitution
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Mater Research Institute-UQ (MRI-UQ)
Official 2014 Collection
School of Medicine Publications
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Created: Thu, 24 Apr 2014, 13:33:45 EST by Dominique Rossouw on behalf of Mater Research Institute-UQ