Identification of a Hematopoietic Cell Population Emerging From Mouse Bone Marrow With Proliferative Potential In Vitro and Immunomodulatory Capacity

Abstract

There is continuing interest in therapeutic applications of bone marrow-derived mesenchymal stromal cells (MSC). Unlike human counterparts, mouse MSC are difficult to propagate in vitro due to their contamination with adherent hematopoietic cells that overgrow the cultures. Here we investigated the properties of these contaminating cells, referred to as bone marrow-derived proliferating hematopoietic cells (BM-PHC). The results showed that both BM-PHC and MSC had strong immunomodulatory properties on T cells in vitro, with PGE2 and NO involved in this mechanism. However, BM-PHC were stronger immunomodulators than MSC, with CCL-6 identified as putative molecule responsible for superior effects. In vivo studies showed that, in contrast to BM-PHC, MSC endorsed a more rapid xenograft tumor rejection, thus indicating a particular context in which only MSC therapy would produce positive outcomes. In conclusion, bone marrow contains two cell populations with immunomodulatory properties, which are valuable sources for therapeutic studies in specific disease-relevant contexts.

All the PNS is a Stage: Transplanted Bone Marrow Cells Play an Immunomodulatory Role in Peripheral Nerve Regeneration

“…Ample evidence supports a powerful immunomodulatory effect of mesenchymal stem cells derived from compartments such as the bone marrow or adipose tissue ( Caplan & Sorrell, 2015 ; Catenaccio et al, 2017 ; Rilo et al, 2017 ; Marinescu et al, 2021 ; Qu et al, 2018 ; Savastano et al, 2014 ) on peripheral and central nervous system injuries ( Aurora & Olson, 2014 ; Brini et al, 2017 ; Evangelista et al, 2018 ; Huh et al, 2017 ; Takahashi et al, 2018 ; Zhang et al, 2013 ). Accordingly, the changes observed in lesion-associated cytokine profiles after BMC administration in different experimental models ( Abreu et al, 2014 ; Brenneman et al, 2010 ; Leal et al, 2014 ) could be at least partially attributed to the small fraction of mesenchymal stem cells present in the suspension after bone marrow extrusion.…”