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Molecular profile and proangiogenic activity of the adipose-derived stromal vascular fraction used as an autologous innovative medicinal product in patients with systemic sclerosis.

Authors
  • Magalon, Jérémy1, 2
  • Velier, Mélanie1, 2
  • Simoncini, Stéphanie2
  • François, Pauline1, 2
  • Bertrand, Baptiste2, 3
  • Daumas, Aurélie4
  • Benyamine, Audrey2, 4
  • Boissier, Romain2, 5
  • Arnaud, Laurent6
  • Lyonnet, Luc6
  • Fernandez, Samantha7
  • Dignat-George, Françoise2, 6
  • Casanova, Dominique3
  • Guillet, Benjamin2, 7
  • Granel, Brigitte2, 4
  • Paul, Pascale1, 2
  • Sabatier, Florence8, 2
  • 1 Cell Therapy Department, Hôpital de la Conception, AP-HM, INSERM CIC BT 1409, Marseille, France. , (France)
  • 2 INSERM, INRA, C2VN, Aix-Marseille University, Marseille, France. , (France)
  • 3 Plastic Surgery Department, Hôpital de la Conception, AP-HM, Marseille, France. , (France)
  • 4 Internal Medicine Department, Hôpital Nord & Hôpital de la Timone, AP-HM, Marseille, France. , (France)
  • 5 Urology Surgery Department, Hôpital de la Conception, AP-HM, Marseille, France. , (France)
  • 6 Vascular Biology Department, Hôpital de la Conception, AP-HM, Marseille, France. , (France)
  • 7 CERIMED, Aix-Marseille University, AP-HM, Marseille, France. , (France)
  • 8 Cell Therapy Department, Hôpital de la Conception, AP-HM, INSERM CIC BT 1409, Marseille, France [email protected] , (France)
Type
Published Article
Journal
Annals of the Rheumatic Diseases
Publisher
BMJ
Publication Date
Mar 01, 2019
Volume
78
Issue
3
Pages
391–398
Identifiers
DOI: 10.1136/annrheumdis-2018-214218
PMID: 30612118
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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. 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. 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. 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. © Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.

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