Solution-Phase Crosstalk and Regulatory Interactions Between Multipotent Adult Progenitor Cells and Peripheral Blood Mononuclear Cells

Abstract

This study documents experiments quantifying solution-phase crosstalk between multipotent adult progenitor cells (MAPCs) and peripheral blood mononuclear cells. The secretome and transcriptional changes quantified suggest mechanisms by which MAPCs are hypothesized to provide both local and systemic immunoregulation of inflammation. The potential impact of these studies includes development of a robust experimental framework to be used for preclinical evaluation of the specific mechanisms by which beneficial effects are obtained after treatment of patients with MAPCs.

Multipotent adult progenitor cells improve the hematopoietic function in myelodysplasia

“…A general secretome analysis of human MAPC cells revealed the presence of molecules that are involved in extracellular matrix regulation and angiogenesis as well as secretion of cytokines that influence cells from the innate and adaptive immune system in their recruitment and effector function [21]. Further examination of the transcriptional and secretome changes induced in PBMCs by MAPC cells (provided in a transwell insert) after activation of T cells, support the hypothesis that MAPC cells block PBMC proliferation by cell cycle arrest via tryptophan depletion [22]. It was also shown that cell surface expression of human leucocyte antigen-DR is minimal on MAPC cells exposed to activated PBMCs, providing a possible explanation of the immuneprivileged MAPC cell status.…”

Multipotent adult progenitor cells induce regulatory T cells and promote their suppressive phenotype via TGFβ and monocyte-dependent mechanisms

“…Like MSCs, MAPC cells have been shown to modulate inflammation in multiple models of injury and disease 11 , 12 , 14 – 19 , 25 , 60 . MAPC cells control immune responses by secreting a milieu of factors with immunomodulatory properties, thus, restoring the inflammatory balance and promoting tissue repair 14 – 16 , 61 .…”

Mesenchymal stromal cells: potential roles in graft‐versus‐host disease prophylaxis and treatment

“…Clearly, the issue of passage number of the MSCs has been raised, and there are suggestions that use of early passage MSCs may have greater efficacy . Better understanding of the MSC secretome and transcriptome, as well as the role of exosomes, will likely influence future product selection . Finally, it is clear that MSC therapy will likely be expensive as the cost of goods and manufacturing, particularly of donor‐directed products, will be far more costly than single production of small molecule therapeutics.…”

“…37 Better understanding of the MSC secretome and transcriptome, as well as the role of exosomes, will likely influence future product selection. 38,39 Finally, it is clear that MSC therapy will likely be expensive as the cost of goods and manufacturing, particularly of donor-directed products, will be far more costly than single production of small molecule therapeutics. Costeffective and comparative effective analyses will be needed in the long term.…”