RT Journal Article
SR Electronic
T1 Molecular profile and proangiogenic activity of the adipose-derived stromal vascular fraction used as an autologous innovative medicinal product in patients with systemic sclerosis
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP 391
OP 398
DO 10.1136/annrheumdis-2018-214218
VO 78
IS 3
A1 Magalon, Jérémy
A1 Velier, Mélanie
A1 Simoncini, Stéphanie
A1 François, Pauline
A1 Bertrand, Baptiste
A1 Daumas, Aurélie
A1 Benyamine, Audrey
A1 Boissier, Romain
A1 Arnaud, Laurent
A1 Lyonnet, Luc
A1 Fernandez, Samantha
A1 Dignat-George, Françoise
A1 Casanova, Dominique
A1 Guillet, Benjamin
A1 Granel, Brigitte
A1 Paul, Pascale
A1 Sabatier, Florence
YR 2019
UL http://ard.bmj.com/content/78/3/391.abstract
AB Objective The autologous stromal vascular fraction (SVF) from adipose tissue is an alternative to cultured adipose-derived stem cells for use in regenerative medicine and represents a promising therapy for vasculopathy and hand disability in systemic sclerosis (SSc). However, the bioactivity of autologous SVF is not documented in this disease context. This study aimed to compare the molecular and functional profiles of the SVF-based medicinal product obtained from SSc and healthy subjects.Methods Good manufacturing practice (GMP)-grade SVF from 24 patients with SSc and 12 healthy donors (HD) was analysed by flow cytometry to compare the distribution of the CD45− and CD45+ haematopoietic cell subsets. The ability of SVF to form a vascular network was assessed using Matrigel in vivo assay. The transcriptomic and secretory profiles of the SSc-SVF were assessed by RNA sequencing and multiplex analysis, respectively, and were compared with the HD-SVF.Results The distribution of the leucocyte, endothelial, stromal, pericyte and transitional cell subsets was similar for SSc-SVF and HD-SVF. SSc-SVF retained its vasculogenic capacity, but the density of neovessels formed in SVF-loaded Matrigel implanted in nude mice was slightly decreased compared with HD-SVF. SSc-SVF displayed a differential molecular signature reflecting deregulation of angiogenesis, endothelial activation and fibrosis.Conclusions Our study provides the first evidence that SSc does not compromise the vascular repair capacity of SVF, supporting its use as an innovative autologous biotherapy. The characterisation of the specific SSc-SVF molecular profile provides new perspectives for delineating markers of the potency of SVF and its targets for the treatment of SSc.