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Engraftment Outcomes after HPC Co-Culture with Mesenchymal Stromal Cells and Osteoblasts
Stem Cell and Regenerative Medicine Group, Biological Therapies Program, Mater Research Institute, University of Queensland, TRI Building, 37 Kent Street, Woolloongabba, Queensland 4102, Australia
School of Medicine, University of Queensland, 288 Herston Road, Herston, Queensland 4006, Australia
Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove Urban Village, Kelvin Grove, Queensland 4059, Australia
Stem Cell and Cancer Group, Biological Therapies Program, Mater Medical Research Institute, Level 3, Aubigny Place, Raymond Terrace, South Brisbane, Queensland 4101, Australia
* Author to whom correspondence should be addressed.
Received: 25 July 2013; in revised form: 22 August 2013 / Accepted: 10 September 2013 / Published: 23 September 2013
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.
Keywords: haematopoietic stem cells; mesenchymal stromal cells; osteoblasts; ex vivo expansion; haematopoietic reconstitution
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Cook, M.M.; Doran, M.R.; Kollar, K.; Barbier, V.; Winkler, I.G.; Levesque, J.-P.; Brooke, G.; Atkinson, K. Engraftment Outcomes after HPC Co-Culture with Mesenchymal Stromal Cells and Osteoblasts. J. Clin. Med. 2013, 2, 115-135.
Cook MM, Doran MR, Kollar K, Barbier V, Winkler IG, Levesque J-P, Brooke G, Atkinson K. Engraftment Outcomes after HPC Co-Culture with Mesenchymal Stromal Cells and Osteoblasts. Journal of Clinical Medicine. 2013; 2(3):115-135.
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." J. Clin. Med. 2, no. 3: 115-135.