Background/Purpose: Broad immune suppression by mesenchymal stem cells (MSCs) make them an attractive candidate as a cell therapy for autoimmune diseases, such as systemic lupus erythematosus (SLE).  MSCs can be derived from various sources and vary slightly depending on the source of origin.  Currently the source of MSCs that will be most effective in ameliorating SLE is unknown.  Moreover, in vivo studies have suggested that lupus derived MSCs are not as effective as MSCs from non-diseased sources.  In this study we assess the suppressive capabilities of MSCs from different sources in vitro.

Methods: To determine the suppressive efficacy of human MSCs we harvested MSCs from healthy donor umbilical cords, bone marrow, and lupus patient bone marrow (n=3-4 of each).  Peripheral blood mononuclear cells (PBMCs) were isolated from healthy individuals and used immediately for cell culture.  PBMCs were labeled with CFSE for detection of suppression.  PBMCs (5×10⁵) were then stimulated with 1μg/ml αCD3/CD28 and co-cultured with varying dilutions of MSCs.  Co-cultures were incubated for 72 hours before cells were collected for flow cytometry and qPCR analysis.  MSC activation was assessed by stimulating 1×10⁵ MSCs with varying concentrations of IFNγ and incubating for 24 hours.  Expression of MSC activation/suppressive markers was assessed by qPCR.

Results:  In comparison to MSCs from healthy donors, lupus MSCs were able to suppress PBMCs equally well.  Only a modest decrease in suppression was seen when lupus MSCs were diluted 1:40 (MSC:PBMC), when compared to healthy MSCs.  We next examined the expression of markers that are important for suppressive MSCs.  Our data showed increased expression of IDO1, CFH, TGFβ and IL6 in lupus MSCs compared to healthy MSCs during PBMC co-culture.  To determine whether lupus MSCs were more readily activated for suppression, we activated the various MSCs with graded doses of IFNγ.  We found that IDO1 and CFH were upregulated in a dose dependant manner similarly in both lupus and healthy MSCs.  However, lupus MSCS had higher expression of IL6, TGFB and T cell attractant chemokines (CXCL9 and CXCL10) when compared to healthy MSCs.

Conclusion: Our results indicate that lupus MSCs are equally as suppressive as healthy MSCs in vitro.  Additionally, certain standard suppressive markers are up regulated in lupus MSCs.  Although our in vitro assessments do not show that lupus MSCs are defective, these results do not correlate with in vivo studies showing reduced capacity of lupus MSCs to mediate disease.  Moreover, our studies suggest that different in vitro evaluations need to be utilized to determine in vivo effectiveness of MSCs.

---

« Back to 2013 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/in-vitro-assessments-of-mesenchymal-stem-cells-from-lupus-patients-to-predict-suppressive-function-in-vivo/