When mesenchymal stem cells (MSCs) are used for therapy of immunological pathologies,
they get into an inflammatory environment, altering the effectiveness of the treatment.
To establish the impact of environmental inflammatory factors on MSCs' immunofunction
in the mirror of intrinsic heterogeneity of mouse MSC population, individual MSC clones
were generated and characterized. Adipogenic but not osteogenic differentiation and
pro-angiogenic activity of five independent MSC cell lines were similar. Regarding
osteogenic differentiation, clones MSC3 and MSC6 exhibited poorer capacity than MSC2,
MSC4, and MSC5. To study the immunosuppressive heterogeneity, in vitro and in vivo
experiments have been carried out using T-cell proliferation assay and delayed-type
hypersensitivity (DTH) response, respectively. A remarkable difference was found between
the clones in their ability to inhibit T-cell proliferation in the following order:
MSC2MSC5>MSC4>MSC3>>MSC6. Nevertheless, the differences between the immunosuppressive
activities of the individual clones disappeared on pretreatment of the cells with
pro-inflammatory cytokines, a procedure called licensing. Stimulation of all clones
with IFN- and TNF- resulted in elevation of their inhibitory capability to a similar
level. Nitric oxide (NO) and prostaglandin E2 (PGE2) were identified as major mediators
of immunofunction of the MSC clones. The earlier findings were also supported by in
vivo results. Without licensing, MSC2 inhibited DTH response, while MSC6 did not affect
DTH response. In contrast, prestimulation of MSC6 with inflammatory cytokines resulted
in strong suppression by this clone as well. Here, we have showed that MSC population
is functionally heterogeneous in terms of immunosuppressive function; however, this
variability is largely reduced under pro-inflammatory conditions.
