Co-culture of hematopoietic stem cells with mesenchymal stem cells increases VCAM-1-dependent migration of primitive hematopoietic stem cells

Abstract

Hematopoietic stem cells (HSC) lose their capacity for engraftment during ex vivo cytokine expansion. It has been shown that mesenchymal stem cells (MSC) improve HSC transplantability; however, the molecular mechanisms responsible for this effect have not yet been completely elucidated. This paper reports that expanding HSC in co-culture with MSC enhances a vascular cell adhesion molecule (VCAM-1)-dependent pro-migratory phenotype. MSC did not regulate the HSC expression of CD49d (VCAM-1 counter-receptor molecule), but did decrease the cytokine-induced HSC VCAM-1-mediated pro-adhesive phenotype. Co-culture with MSC reduced the expression of the inactive conformation of lymphocyte function-associated antigen (LFA-1) at the HSC uropod, and induced higher expression of an LFA-1 activation epitope. Interestingly, VCAM-1-dependent HSC migration was modulated by targeting this LFA-1 high affinity form, suggesting integrin cross-regulation. VCAM-1-mediated HSC transmigration appeared to favor the more primitive HSC immunophenotype. Our results suggested that co-culture with MSC improved VCAM-1-dependent migration of primitive HSC, which was affected in ex vivo cytokine-expanded HSCs by a mechanism involving LFA-1 modulation.

Co-Activation of PKC-δ by CRIF1 Modulates Oxidative Stress in Bone Marrow Multipotent Mesenchymal Stromal Cells after Irradiation by Phosphorylating NRF2 Ser40

“…Considering the results of our previous study and the current study, we provided several pieces of evidence indicating that CRIF1, which was highly expressed in BMMSCs, may have multiple functions in pathology and physiology after radiation damage. Several studies have described the HSCs-supporting function of BMMSCs 54 - 56 . According to our in vitro results of the CFU assay in BMMNCs co-cultured with irradiated BMMSCs, we speculated that CRIF1 may be helpful for the HSCs-supporting function of BMMSCs after irradiation.…”

Identification of New Rat Bone Marrow‐Derived Population of Very Small Stem Cell with Oct‐4A and Nanog Expression by Flow Cytometric Platforms

“…Similarly, CD106 (VCAM-1) may be expressed not only on mature myeloid cells, splendid dendritic cells, or induced endothelial cells, but also on more primitive bone marrow stem/stromal cells [ 40 ]. CD106 represents a counterreceptor for VLA-4 ( α 4 β 1 integrin) [ 41 ] and the interactions between these molecules may play an important role in binding of leukocytes to activated endothelial cells and leukocyte extravasation at inflammatory sites as well as in stem cell migration [ 41 , 42 ].…”

The Potential of Cytotherapeutics in Hematologic Reconstitution and in the Treatment and Prophylaxis of Graft-Versus-Host Disease. Chapter II: Emerging Transformational Cytotherapies

“…Among the changes this technique brings, it appears that expanding HSCs in coculture with MSC results in the enhancement of the vascular cell adhesion moleculedependent migration of primitive HSCs, which is typically affected in ex vivo cytokine-expanded HSCs [106]. Similarly, human umbilical cord Wharton's jelly stem cells and their conditioning medium were used as an expansion matrix to leverage the supportive effect of MSCs, resulting in a significant increase in the number of CD34 + cells contained in the expanded sample [107].…”