Inter-center comparison of good manufacturing practices-compliant stromal vascular fraction and proposal for release acceptance criteria: a review of 364 productions

Stem Cell Research & Therapy

Françoise Dignat-George¹  Audrey Cras²  Fanny Grimaud³  Chloé Dumoulin³  Laurent Giraudo³  Julie Veran³  Pauline François⁴  Jeremy Magalon⁵  Florence Sabatier⁵  Camille Giverne⁶  Dominique Casanova⁷  Baptiste Bertrand⁷  Guy Magalon⁸  Greta Minonzio⁹  Gianni Soldati⁹  Luca Mariotta⁹  Giulio Rusconi^1,10  Laurent Arnaud^1,11  Luc Lyonnet^1,11 

[1] Aix Marseille Univ, INSERM, INRA, C2VN, Marseille, France;Vascular Biology Department, Hôpital de la Conception, AP-HM, Marseille, France;Assistance Publique-Hôpitaux de Paris, Saint-Louis Hospital, Cell Therapy Unit, Cord blood Bank and CIC-BT501, Paris, France;Cell Therapy Department, Hôpital de la Conception, AP-HM, INSERM CIC BT 1409, 147 Bd Baille, 13005, Marseille, France;Cell Therapy Department, Hôpital de la Conception, AP-HM, INSERM CIC BT 1409, 147 Bd Baille, 13005, Marseille, France;Aix Marseille Univ, INSERM, INRA, C2VN, Marseille, France;Cell Therapy Department, Hôpital de la Conception, AP-HM, INSERM CIC BT 1409, 147 Bd Baille, 13005, Marseille, France;Aix Marseille Univ, INSERM, INRA, C2VN, Marseille, France;Remedex, Marseille, France;Normandie Univ, UNIROUEN, INSERM, U1234, Rouen University Hospital, Department of Immunology and Biotherapy, Rouen, France;Plastic Surgery Department, Hôpital de la Conception, AP-HM, Marseille, France;Remedex, Marseille, France;Swiss Stem Cell Foundation, Gentilino, Lugano, Switzerland;Swiss Stem Cell Foundation, Gentilino, Lugano, Switzerland;Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy;Vascular Biology Department, Hôpital de la Conception, AP-HM, Marseille, France;

关键词: Stromal vascular fraction;    Adipose tissue;    Cell subset distribution;    Flow cytometry;    GMP production;    Advanced therapy medicinal product;   

DOI  :  10.1186/s13287-021-02445-z

来源: Springer

【 摘 要 】

BackgroundEven though the manufacturing processes of the stromal vascular fraction for clinical use are performed in compliance with the good manufacturing practices applying to advanced therapy medicinal products, specifications related to stromal vascular fraction quality remain poorly defined. We analyzed stromal vascular fraction clinical batches from two independent good manufacturing practices-compliant manufacturing facilities, the Swiss Stem Cell Foundation (SSCF) and Marseille University Hospitals (AP-HM), with the goal of defining appropriate and harmonized release acceptance criteria.MethodsThis retrospective analysis reviewed the biological characteristics of 364 batches of clinical-grade stromal vascular fraction. Collected data included cell viability, recovery yield, cell subset distribution of stromal vascular fraction, and microbiological quality.ResultsStromal vascular fraction from SSCF cohort demonstrated a higher viability (89.33% ± 4.30%) and recovery yield (2.54 × 105 ± 1.22 × 105 viable nucleated cells (VNCs) per mL of adipose tissue) than stromal vascular fraction from AP-HM (84.20% ± 5.96% and 2.25 × 105 ± 1.11 × 105 VNCs per mL). AP-HM batches were significantly less contaminated (95.71% of sterile batches versus 74.15% for SSCF batches). The cell subset distribution was significantly different (higher proportion of endothelial cells and lower proportion of leukocytes and pericytes in SSCF cohort).ConclusionsBoth centers agreed that a good manufacturing practices-compliant stromal vascular fraction batch should exert a viability equal or superior to 80%, a minimum recovery yield of 1.50 × 105 VNCs per mL of adipose tissue, a proportion of adipose-derived stromal cells at least equal to 20%, and a proportion of leukocytes under 50%. In addition, a multiparameter gating strategy for stromal vascular fraction analysis is proposed.

【 授权许可】

CC BY