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J. Clin. Med. 2013, 2(3), 115-135; doi:10.3390/jcm2030115
Article

Engraftment Outcomes after HPC Co-Culture with Mesenchymal Stromal Cells and Osteoblasts

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Received: 25 July 2013; in revised form: 22 August 2013 / Accepted: 10 September 2013 / Published: 23 September 2013
(This article belongs to the Special Issue Frontiers in Stem Cell Treatments)
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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 haematopoietic stem cells; mesenchymal stromal cells; osteoblasts; ex vivo expansion; haematopoietic reconstitution
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

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.

AMA Style

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.

Chicago/Turabian Style

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.

J. Clin. Med. EISSN 2077-0383 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert