Abstract

Abstract It has been shown that adipose-derived mesenchymal stem cells (AMSCs) can differentiate into red blood cells and epithelial cells as well as mesenchymal cells such as adipocytes, chondrocytes and osteoblasts. Various clinical trials have shown the ability of AMSCs to regenerate these cell types. Age-associated dysregulation of the gastrointestinal (GI) immune system has been well documented. Our previous studies showed that impaired mucosal immunity in the GI tract occurs earlier than is seen in the systemic compartment. In this study, we examined the potential of AMSCs to restore the GI mucosal immune system in aged mice. Aged (>2yr) mice were adoptively transferred with AMSCs. Two weeks later, mice were orally immunized with ovalbumin (OVA) plus cholera toxin three times at weekly intervals. Seven days after the final immunization, when fecal extract samples and plasma were subjected to OVA-specific ELISA, elevated levels of mucosal secretory IgA (SIgA) and plasma IgG antibody (Ab) responses were noted in aged mouse recipients. When cytokine production was examined, OVA-stimulated Peyer’s patch CD4+ T cells produced increased levels of IL-4. Further, CD4+ T cells from the lamina propria revealed elevated levels of IL-4 and IFN-γ production. In contrast, aged mice without AMSC transfer showed essentially no OVA-specific mucosal SIgA or plasma IgG Ab or cytokine responses. These results suggest that AMSCs can restore impaired mucosal immunity in the GI tract of aged mice.

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