Abstract
It has been shown that adipose-derived mesenchymal stem cells (AMSCs) can differentiate into adipocytes, chondrocytes and osteoblasts. Several clinical trials have shown the ability of AMSCs to regenerate these differentiated 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 during agingthan 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 (>18 mo old) mice were adoptively transferred with AMSCs. Two weeks later, mice were orally immunized with ovalbumin (OVA) plus cholera toxin (CT) three times at weekly intervals. Seven days after the final immunization, when fecal extract samples and plasma were subjected to OVA- and CT-B-specific ELISA, elevated levels of mucosal secretory IgA (SIgA) and plasma IgG antibody (Ab) responses were noted in aged mouse recipients. Similar results were also seen aged mice which received AMSCs at one year of age. 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- or CT-B-specific mucosal SIgA or plasma IgG Ab or cytokine responses. Of importance, fecal extracts from AMSC transferred aged mice showed neutralization activity to CT intoxication. These results suggest that AMSCs can restore impaired mucosal immunity in the GI tract of aged mice.
Highlights
Immune functions deteriorate with age in several species [1,2,3,4,5,6]
HAMSCs were adoptively transferred into two-year old mice and the mice were orally immunized with OVA plus cholera toxin (CT) as mucosal adjuvant
Since our previous studies showed that IL-4 production by Ag-specific CD4+ T cells play an essential role in the induction of secretory IgA (SIgA) Ab responses when CT was employed as a mucosal adjuvant [34, 35], we examined Ag-stimulated Th1- and Th2-type cytokine responses in aged mice with or without mAMSC transfer
Summary
Immune functions deteriorate with age in several species [1,2,3,4,5,6]. In humans, the elderly are at a higher risk for infections, especially influenza virus and Streptococcus pneumoniae, as well as PLOS ONE | DOI:10.1371/journal.pone.0148185 February 3, 2016Mucosal Immunoregulatory Functions of Mesenchymal Stem CellsThis does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.for certain autoimmune diseases and cancer, and their immune responses to vaccination are diminished [7,8,9,10,11]. Mucosal Immunoregulatory Functions of Mesenchymal Stem Cells This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials. It has been suggested that certain dendritic cell (DC) populations are fully functional in aging, both foreignand self-antigens (Ags) induce enhanced proinflammatory cytokines [2, 5, 10, 12]. This enhanced inflammation can be detrimental; very old individuals with a more balanced pro- and anti- inflammatory phenotype may be the most fortunate. The association of inflammation in aging has been termed “inflamm aging”; we still do not have direct evidence that inflamm aging occurs in and influences the mucosal immune system [13]
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