Aging, rather than Parkinson's disease, affects the responsiveness of PBMCs to the immunosuppression of bone marrow mesenchymal stem cells.

Abstract

Whether aging or Parkinson's disease (PD) affects the responses of peripheral blood mononuclear cells (PBMCs) to immunosuppression by bone marrow-derived mesenchymal stem cell (BM-MSCs) and which cytokines are more effective in inducing BM-MSCs to be immunosuppressive remains to be elucidated. PBMCs were isolated from healthy young (age 26–35), healthy middle-aged (age 56–60) and middle-aged PD-affected individuals. All the recruits were male. The mitogen-stimulated PBMCs and proinflammatory cytokine-pretreated BM-MSCs were co-cultured. The PBMC proliferation was measured using Cell Counting Kit-8, while the cytokine secretion was assayed by cytometric bead array technology. The immunosuppressive ability of BM-MSCs was confirmed in young healthy, middle-aged healthy and middle-aged PD-affected individuals. Among the three groups, the PBMC proliferation and cytokine secretion of the young healthy group were suppressed more significantly compared with those of the middle-aged healthy and middle-aged PD-affected group. No significant differences were identified in the PBMC proliferation and cytokine secretion between the patients with PD and the middle-aged healthy subjects. Interferon (IFN)-γ synergized with tumor necrosis factor (TNF)-α, interleukin (IL)-1α or IL-1β was more effective than either one alone, and the combinations of IFN-γ + IL-1α and IFN-γ + IL-1β were more effective than IFN-γ + TNF-α in inducing BM-MSCs to inhibit PBMC proliferation. The results of the present study suggested that aging, rather than PD, affects the response of PBMCs toward the suppression of BM-MSC, at least in middle-aged males. Patients with PD aged 56–60 remain eligible for anti-inflammatory BM-MSC-based therapy. Treatment of BM-MSCs with IFN-γ + IL-1α or IFN-γ + IL-1β prior to transplantation may result in improved immunosuppressive effects.