title: Adipose-Derived Mesenchymal Stem Cells Restore Impaired Mucosal Immune Responses in Aged Mice.
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.
authors: Department of Pediatric Dentistry, The University of Alabama at Birmingham, Birmingham, AL, United States of America.
authors: Kazuyoshi
authors: K
authors: Aso
authors: Department of Pediatric Dentistry, The University of Alabama at Birmingham, Birmingham, AL, United States of America.
authors: Akitoshi
authors: A
authors: Tsuruhara
authors: BioMimetics Sympathies Inc., Tokyo, Japan.
authors: Kentaro
authors: K
authors: Takagaki
authors: BioMimetics Sympathies Inc., Tokyo, Japan.
authors: Katsuyuki
authors: K
authors: Oki
authors: BioMimetics Sympathies Inc., Tokyo, Japan.
authors: Megumi
authors: M
authors: Ota
authors: BioMimetics Sympathies Inc., Tokyo, Japan.
authors: Yasuhiro
authors: Y
authors: Nose
authors: BioMimetics Sympathies Inc., Tokyo, Japan.
authors: Hideki
authors: H
authors: Tanemura
authors: BioMimetics Sympathies Inc., Tokyo, Japan.
authors: Naoki
authors: N
authors: Urushihata
authors: Department of Neurosurgery, Shinyurigaoka General Hospital, Kawasaki, Japan.
authors: Jinichi
authors: J
authors: Sasanuma
authors: Sunfield Clinic, Koto-ku, Tokyo, Japan.
authors: Masayuki
authors: M
authors: Sano
authors: Sunfield Clinic, Koto-ku, Tokyo, Japan.
authors: Atsuyuki
authors: A
authors: Hirano
authors: Department of Pediatric Dentistry, The University of Alabama at Birmingham, Birmingham, AL, United States of America.
authors: Rio
authors: R
authors: Aso
authors: Department of Pediatric Dentistry, The University of Alabama at Birmingham, Birmingham, AL, United States of America.
authors: Jerry R
authors: JR
authors: McGhee
authors: Department of Pediatric Dentistry, The University of Alabama at Birmingham, Birmingham, AL, United States of America.
authors: Kohtaro
authors: K
authors: Fujihashi
mesh_terms: D000273:Adipose Tissue / Q000276:immunology*; D000375:Aging / Q000276:immunology*; D064591:Allografts; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002772:Cholera Toxin / Q000633:toxicity; D005260:Female; D018928:Immunity, Mucosal; D007071:Immunoglobulin A, Secretory / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D051379:Mice; D010581:Peyer's Patches / Q000276:immunology*
chemical_list: D007071:Immunoglobulin A, Secretory; D015847:Interleukin-4; D007371:Interferon-gamma; D002772:Cholera Toxin