title: In vitro allogeneic immune cell response to mesenchymal stromal cells derived from human adipose in patients with rheumatoid arthritis.
abstract: We investigated the regulatory activity of human adipose-derived mesenchymal stromal cells (MSCs) (n=10) towards immune cells in a cohort of 84 rheumatoid arthritis (RA) patients, 36 apparently healthy controls. We co-cultured MSCs with lymphocyte subsets of T, B, and T regulatory cells (Tregs). Levels of the pro- and anti-inflammatory markers (tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), and interleukin-10 (IL-10)) were estimated in serum and co-culture supernatants. The study revealed a two-fold increase in the proportion of Tregs and an increased level of CD4+CD25+FoxP3. MSCs altered T cell, B cell, and Treg cytokine production during an anti-inflammatory immune response. The MSCs inhibited CD3+T cell-mediated TNF-α secretion, upregulated IL-10, and suppressed the production of autoantibodies against citrullinated protein antigens produced by B cells. These data offer insight into the interactions between allogeneic MSCs and immune cells, and elucidate the dose-dependent modulation of MSCs.
authors.affiliation: Transplant Biology, Immunology & Stem Cell Unit, Global Hospitals, Hyderabad, India.
authors.forename: P
authors.initials: P
authors.lastname: Usha Shalini
authors.affiliation: Department of Orthopedics, Aware Global Hospitals, Hyderabad, India.
authors.forename: J V S
authors.initials: JV
authors.lastname: Vidyasagar
authors.affiliation: Department of Bariatric Surgery, Global Hospitals, Hyderabad, India.
authors.forename: Lakshmi Kumari
authors.initials: LK
authors.lastname: Kona
authors.affiliation: Transplant Biology, Immunology & Stem Cell Unit, Global Hospitals, Hyderabad, India.
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Ponnana
authors.affiliation: Transplant Biology, Immunology & Stem Cell Unit, Global Hospitals, Hyderabad, India. Electronic address: lkiran@globalhospitalsindia.com.
authors.forename: Lakshmi Kiran
authors.initials: LK
authors.lastname: Chelluri
mesh_terms: D000273:Adipose Tissue / Q000473:pathology*; D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000097:blood; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000628:therapy*; D002478:Cells, Cultured; D002956:Citrulline / Q000737:chemistry; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007109:Immunity; D007167:Immunotherapy / Q000379:methods*; D018836:Inflammation Mediators / Q000378:metabolism; D007519:Isoantigens / Q000737:chemistry / Q000276:immunology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D055815:Young Adult
chemical_list: D000906:Antibodies; D016207:Cytokines; D018836:Inflammation Mediators; D007519:Isoantigens; D002956:Citrulline
keywords: Human adipose-derived stem cells; Immunomodulation; Immunosuppression; Mesenchymal stromal cells; Rheumatoid arthritis