OR11
Development of a human umbilical cord-derived mesenchymal stromal cell (UC-MSC)-based advanced therapy medicinal product (ATMP) to treat immune and/or inflammatory diseases
M Mebarki ¹ ² ³ ⁴ N Iglicki ³ C Marigny ³ C Abadie ³ C Nicolet ³ G Churlaud ⁵ C Maheux ⁵ H Boucher ⁵ A Monsel ⁶ ⁷ P Menasché ⁸ J Larghero ¹ ³ ⁴ ⁵ L Faivre ¹ ³ ⁴ A Cras ² ³ ⁴ ⁹
1: INSERM U976, Université de Paris 2: Faculté de Pharmacie, Université de Paris 3: Centre d'investigation Clinique de Biothérapies CBT501 4: Unité de Thérapie Cellulaire, Hôpital Saint-Louis, AP-HP 5: Centre MEARY de Thérapie Cellulaire Et Génique, AP-HP, Hôpital Saint-Louis 6: Unité de Soins Intensifs Et Département de Biothérapies, inflammation et immunopathologie, AP-HP, Hôpital La Pitié-Salpêtrière 7: INSERM UMR-S 959, Université Sorbonne 8: Département de Chirurgie Cardiovasculaire, AP-HP, Hôpital Européen Georges Pompidou 9: INSERM UMR1140, Université de Paris
Immune regulation by UC-MSCs offers promising perspectives to treat immune and inflammatory diseases. Our aim was to develop a production process of an UC-MSC-based ATMP and to characterize UC-MSC properties and immunomodulatory activities in vitro.
Among 15 collected umbilical cords (UCs), 12 were processed successfully allowing to isolate UC-MSCs. Three batches from a single donor were characterized at basal state and after in vitro proinflammatory stimulation by interferon-γ (IFNγ) and tumor necrosis factor-α (TNFα). Cell morphology, proliferation and phenotype were not modified by inflammatory treatment. CD90, CD105, CD73, CD44, CD29, CD166 expression was positive; CD14, CD45, CD31, HLA-DR, CD40, CD80 and CD86 negative, while CD146 and HLA-ABC were heterogeneous. Indoleamine 2,3-dioxygenase (IDO), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) expression was induced significantly after priming. T cell proliferation was significantly decreased in the presence of UC-MSCs in a dose-dependent manner. This inhibitory effect was improved by IFNγ and IFNγ + TNFα. Finally, this technology was transferred to a good manufacturing practice-compliant facility to manufacture an experimental ATMP for clinical use (NCT04333368).
Our results showed that an inflammatory environment preserves the biological properties of UC-MSCs while improving their immunomodulatory functions. Our perspective is to compare UC-MSC properties and functions between several donors then with a pool of donors, in order to determine the best strategy to develop UC-MSC-based ATMPs.