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

Journal of Clinical Medicine

Matthew M. Cook¹  Michael R. Doran¹  Katarina Kollar¹  Valerie Barbier³  Ingrid G. Winkler³  Jean-Pierre Levesque²  Gary Brooke¹ 

[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; E-Mails:;School of Medicine, University of Queensland, 288 Herston Road, Herston, Queensland 4006, Australia; E-Mail:;Stem Cell and Cancer Group, Biological Therapies Program, Mater Medical Research Institute, Level 3, Aubigny Place, Raymond Terrace, South Brisbane, Queensland 4101, Australia; E-Mails:

关键词: haematopoietic stem cells;    mesenchymal stromal cells;    osteoblasts;    ex vivo expansion;    haematopoietic reconstitution;   

DOI  :  10.3390/jcm2030115

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.