Abstract
Mesenchymal Stromal Cells (MSC) have been shown to exhibit immuno-modulatory and regenerative properties at sites of inflammation. In solid organ transplantation (SOT), administration of MSCs might lead to an alleviation of ischemia-reperfusion injury and a reduction of rejection episodes. Previous reports have suggested ‘MSC-preconditioning’ of macrophages to be partly responsible for the beneficial effects. Whether this results from direct cell-cell interactions (e.g., MSC trans-differentiation at sites of damage), or from paracrine mechanisms, remains unclear. Immunosuppressive capacities of MSCs from donors of different age and from genetically modified donor animals, often used for in-vivo experiments, have so far not been investigated. We conducted an in vitro study to compare paracrine effects of supernatants from MSCs extracted from young and old wild-type Wystar-Kyoto rats (WKY-wt), as well as young and old WKY donor rats positive for the expression of green fluorescent protein (WKY-GFP), on bone marrow derived macrophages (BMDM). Expression levels of Mannose receptor 1 (Mrc-1), Tumor necrosis factor α (TNFα), inducible NO synthase (iNos) and Interleukin-10 (IL-10) in BMDMs after treatment with different MSC supernatants were compared by performance of quantitative PCR. We observed different expression patterns of inflammatory markers within BMDMs, depending on age and genotype of origin for MSC supernatants. This must be taken into consideration for preclinical and clinical studies, for which MSCs will be used to treat transplant patients, aiming to mitigate inflammatory and allo-responses.
Highlights
Mesenchymal Stromal Cells (MSC) are multipotent, self-renewing cells which have been shown to exhibit immuno-modulatory, anti-inflammatory and regenerative capacities at sites of inflammation [1,2,3]
MSCs secrete a range of anti-inflammatory factors, including Interleukin-10 (IL-10), Transforming growth factor-beta (TGF-beta), hepatocyte growth factor (HGF), nitric oxide (NO), Histocompatibility antigen-G (HLA-G) and Prostaglandin E2 (PGE2), that are all indicated to play some role in their immunomodulatory effect [9,12,13]
MSCs extracted from the bone marrows of green fluorescent protein (GFP) positive rats, showed green fluorescence, confirmed by confocal microscopy, and by flow cytometry
Summary
Mesenchymal Stromal Cells (MSC) are multipotent, self-renewing cells which have been shown to exhibit immuno-modulatory, anti-inflammatory and regenerative capacities at sites of inflammation [1,2,3]. Via the secretion of cytokines, growth factors and prostaglandins with immune-modulatory and regenerative function, MSCs may target resident cells. Several reports have suggested ‘MSC-preconditioned’ macrophage activation to be partly responsible for the beneficial effects [15,16,17]. Whether these result from direct cell-cell interactions in the sense of an MSC trans-differentiation at sites of damage, or from paracrine mechanisms, remains unclear
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
