Background: Direct comparison of the immunoregulatory properties of mesenchymal stem cells derived from bone marrow (BMSCs) and adipose tissue (ASCs) has not been performed to date. Moreover, the impact of cell senescence and donor age on alloimmune regulation of these cell types is unknown. In this study we addressed this gap and performed a head-to-head in vitro comparison of the immunoregulatory effects of BMSCs and ASCs from juvenile and senile rats.

Methods: BMSCs and ASCs were isolated from juvenile and senile Lewis, Brown Norway (BN), and ACI rats; sorted and re-characterized. A Lewis vs. BN mixed lymphocyte reaction was set up, and co-cultured with various doses (1:1,000-1:10,000 regulator vs. responder) of different MSCs (Young, Senile and MSCs from Passage 5). Culture media was harvested from stem cell cultures to assess for cell contact independent immunoregulatory effects. In addition, MSCs were added on day 3 to the MLR (delayed regulation), or were removed after 3-day of co-culture from the MLR (interrupted regulation).

Results: BMSCs and ASCs of all juvenile strains showed similar biological properties. In contrast, MSCs isolated from senile rats exhibited irregular morphology, slower expansion and lower yield (p<0.05) by FACS. When added to allogeneic MLRs, both BMSCs and ASCs of different origins (recipient, donor and third party) significantly suppressed allogeneic and PHA stimulation in a dose-dependent manner (p<0.05). ASCs proved superior to BM-SCs in reduction of both allogeneic and non-specific stimulation (p<0.05). Stem cell culture media alone, however, did not suppress proliferation of mixed lymphocytes in any group. Moreover, both delayed and interrupted regulation displayed reduced suppressive effects (suppression rate: 16.22% and 50.41% vs. 83.39% displayed in day 0 co-cultures). MSCs isolated from senile subjects as well as from late passage exhibited lower regulatory potentials (10.91% vs. 64.49%).

Conclusions: BMSCs and ASCs, independent of their origin (donor, recipient or third party), exert potent immunomodulation in allogeneic and in PHA-induced stimulation. However, their regulatory potential decreases with cell senescence. As soluble factors do not seem to play a role in immunoregulation, cell-cell interaction represents the main mechanism of immunomodulation by MSCs.

« Back to 2013 American Transplant Congress