J. Clin. Med. 2013, 2(3), 115-135; doi:10.3390/jcm2030115
Engraftment Outcomes after HPC Co-Culture with Mesenchymal Stromal Cells and Osteoblasts
1
Stem Cell and Regenerative Medicine Group, Biological Therapies Program, Mater Research Institute, University of Queensland, TRI Building, 37 Kent Street, Woolloongabba, Queensland 4102, Australia
2
School of Medicine, University of Queensland, 288 Herston Road, Herston, Queensland 4006, Australia
3
Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove Urban Village, Kelvin Grove, Queensland 4059, Australia
4
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 / Revised: 22 August 2013 / Accepted: 10 September 2013 / Published: 23 September 2013
(This article belongs to the Special Issue Frontiers in Stem Cell Treatments)
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. View Full-TextKeywords:
haematopoietic stem cells; mesenchymal stromal cells; osteoblasts; ex vivo expansion; haematopoietic reconstitution
▼
Figures
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
Share & Cite This Article
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.
Related Articles
Article Metrics
Comments
[Return to top]
J. Clin. Med.
EISSN 2077-0383
Published by MDPI AG, Basel, Switzerland
RSS
E-Mail Table of Contents Alert