Bone Marrow Mesenchymal Stromal Cells Isolated From Multiple Sclerosis Patients Have Distinct Gene Expression Profile and Decreased Suppressive Function Compared With Healthy Counterparts

Author(s):Show less -

de Oliveira, Gislane L. V. ^{[1, 2]} ; de Lima, Kalil W. A. ^{[1, 2]} ; Colombini, Amanda M. ^[2] ; Pinheiro, Daniel G. ^[2] ; Panepucci, Rodrigo A. ^[2] ; Palma, Patricia V. B. ^[2] ; Brum, Doralina G. ^[3] ; Covas, Dimas T. ^{[2, 4]} ; Simoes, Belinda P. ^{[2, 4]} ; de Oliveira, Maria C. ^{[2, 4]} ; Donadi, Eduardo A. ^[4] ; Mamegrim, Kelen C. R. ^{[2, 5]}

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Biochem & Immunol, BR-14049 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Reg Blood Ctr Ribeirao Preto, Ctr Cell Based Res, BR-14049 Ribeirao Preto, SP - Brazil

^[3] Univ State Sao Paulo, Sch Med Botucatu, Dept Neurol Psychol & Psychiat, Botucatu, SP - Brazil

^[4] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Clin Med, BR-14049 Ribeirao Preto, SP - Brazil

^[5] Univ Sao Paulo, Fac Pharmaceut Sci Ribeirao Preto, Dept Clin Toxicol & Bromatol Anal, BR-14049 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: CELL TRANSPLANTATION; v. 24, n. 2, p. 151-165, 2015.
• Web of Science Citations: 24

Abstract

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system, due to an immune reaction against myelin proteins. Multipotent mesenchymal stromal cells (MSCs) present immunosuppressive effects and have been used for the treatment of autoimmune diseases. In our study, gene expression profile and in vitro immunomodulatory function tests were used to compare bone marrow-derived MSCs obtained from MS patients, at pre- and postautologous hematopoietic stem cell transplantation (AHSCT) with those from healthy donors. Patient MSCs comparatively exhibited i) senescence in culture; ii) similar osteogenic and adipogenic differentiation potential; iii) decreased expression of CD 105, CD73, CD44, and HLA-A/B/C molecules; iv) distinct transcription at pre-AHSCT compared with control MSCs, yielding 618 differentially expressed genes, including the downregulation of TGFBI and HGF genes and modulation of the FGF and HGF signaling pathways; v) reduced antiproliferative effects when pre-AHSCT MSCs were cocultured with allogeneic T-lymphocytes; vi) decreased secretion of IL-10 and TGF-beta in supernatants of both cocultures (pre- and post-AHSCT MSCs); and vii) similar percentages of regulatory cells recovered after MSC cocultures. The transcriptional profile of patient MSCs isolated 6 months posttransplantation was closer to pre-AHSCT samples than from healthy MSCs. Considering that patient MSCs exhibited phenotypic changes, distinct transcriptional profile and functional defects implicated in MSC immunomodulatory and immunosuppressive activity, we suggest that further MS clinical studies should be conducted using allogeneic bone marrow MSCs derived from healthy donors. We also demonstrated that treatment of MS patients with AHSCT does not reverse the transcriptional and functional alterations observed in patient MSCs. (AU)