Article Text

PDF
Molecular profile and proangiogenic activity of the adipose-derived stromal vascular fraction used as an autologous innovative medicinal product in patients with systemic sclerosis
  1. Jérémy Magalon1,2,
  2. Mélanie Velier1,2,
  3. Stéphanie Simoncini2,
  4. Pauline François1,2,
  5. Baptiste Bertrand2,3,
  6. Aurélie Daumas4,
  7. Audrey Benyamine2,4,
  8. Romain Boissier2,5,
  9. Laurent Arnaud6,
  10. Luc Lyonnet6,
  11. Samantha Fernandez7,
  12. Françoise Dignat-George2,6,
  13. Dominique Casanova3,
  14. Benjamin Guillet2,7,
  15. Brigitte Granel2,4,
  16. Pascale Paul1,2,
  17. Florence Sabatier1,2
  1. 1 Cell Therapy Department, Hôpital de la Conception, AP-HM, INSERM CIC BT 1409, Marseille, France
  2. 2 INSERM, INRA, C2VN, Aix-Marseille University, Marseille, France
  3. 3 Plastic Surgery Department, Hôpital de la Conception, AP-HM, Marseille, France
  4. 4 Internal Medicine Department, Hôpital Nord & Hôpital de la Timone, AP-HM, Marseille, France
  5. 5 Urology Surgery Department, Hôpital de la Conception, AP-HM, Marseille, France
  6. 6 Vascular Biology Department, Hôpital de la Conception, AP-HM, Marseille, France
  7. 7 CERIMED, Aix-Marseille University, AP-HM, Marseille, France
  1. Correspondence to Professor Florence Sabatier, Cell Therapy Department, Hôpital de la Conception, Assistance Publique Hôpitaux de Marseille, Marseille 13005, France; florence.sabatier{at}ap-hm.fr

Abstract

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.

  • systemic sclerosis
  • autoimmune diseases
  • hand osteoarthritis

Statistics from Altmetric.com

Footnotes

  • Handling editor Josef S Smolen

  • Contributors Study concept and design: JM, SS, PP, FS. Collection and acquisition of data: JM, MV, BB, AD, AB, RB. Analysis and interpretation of data: JM, PF, LA, LL. In vivo experiments including interpretation: LL, SF, BeG. Drafting of the manuscript: JM, PF, MV, BB. Critical revision of the manuscript for important intellectual content: FD-G, BeG, BrG, PP, FS . Study supervision: FD-G, DC, PP, FS.

  • Funding Funding for this work was granted by Fondation de l’Avenir (Grant APM RMA 2015-0008) and AORC Junior 2017 from Assistance Publique Hopitaux Marseille.

  • Disclaimer We certify that the manuscript was edited for proper English language, grammar, punctuation, spelling and overall style by one or more of the highly qualified native English-speaking editors at American Journal Experts (Certificate Verification Key 9067-71A5-5CFD-7DC1-18AP).

  • Competing interests None declared.

  • Patient consent for publication Obtained.

  • Ethics approval The protocol was approved by the local ethics committee (authorisation #14.051 from CPP Sud Méditerranée V) and the National Health Regulatory Authority (authorisation #141 449 A-62 from ANSM).

  • Provenance and peer review Not commissioned; externally peer reviewed.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.