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.