Inactivated Platelet Lysate Supports the Proliferation and Immunomodulant Characteristics of Mesenchymal Stromal Cells in GMP Culture Conditions
Katia Mareschi,
Sara Castiglia,
Aloe Adamini,
Deborah Rustichelli,
Elena Marini,
Alessia Giovanna Santa Banche Niclot,
Massimiliano Bergallo,
Luciana Labanca,
Ivana Ferrero,
Franca Fagioli
Affiliations
Katia Mareschi
Department of Public Health and Paediatrics, The University of Turin, Piazza Polonia 94, 10126 Torino, Italy
Sara Castiglia
Stem Cell Transplantation and Cellular Therapy Laboratory, Paediatric Onco-Haematology Division, Regina Margherita Children’s Hospital, City of Health and Science of Turin, 10126 Torino, Italy
Aloe Adamini
Stem Cell Transplantation and Cellular Therapy Laboratory, Paediatric Onco-Haematology Division, Regina Margherita Children’s Hospital, City of Health and Science of Turin, 10126 Torino, Italy
Deborah Rustichelli
Stem Cell Transplantation and Cellular Therapy Laboratory, Paediatric Onco-Haematology Division, Regina Margherita Children’s Hospital, City of Health and Science of Turin, 10126 Torino, Italy
Elena Marini
Department of Public Health and Paediatrics, The University of Turin, Piazza Polonia 94, 10126 Torino, Italy
Alessia Giovanna Santa Banche Niclot
Department of Public Health and Paediatrics, The University of Turin, Piazza Polonia 94, 10126 Torino, Italy
Massimiliano Bergallo
Department of Public Health and Paediatrics, The University of Turin, Piazza Polonia 94, 10126 Torino, Italy
Luciana Labanca
Blood Component Production and Validation Center, City of Health and Science of Turin, S. Anna Hospital, 10126 Turin, Italy
Ivana Ferrero
Stem Cell Transplantation and Cellular Therapy Laboratory, Paediatric Onco-Haematology Division, Regina Margherita Children’s Hospital, City of Health and Science of Turin, 10126 Torino, Italy
Franca Fagioli
Department of Public Health and Paediatrics, The University of Turin, Piazza Polonia 94, 10126 Torino, Italy
Mesenchymal stromal cells (MSCs) isolated from bone marrow (BM-MSCs) are considered advanced therapy medicinal products (ATMPs) and need to be produced according to good manufacturing practice (GMP) in their clinical use. Human platelet lysate (HPL) is a good GMP-compliant alternative to animal serum, and we have demonstrated that after pathogen inactivation with psoralen, it was safer and more efficient to use psoralen in the production of MSCs following GMP guidelines. In this study, the MSCs cultivated in fetal bovine serum (FBS-MSC) or inactivated HPL (iHPL-MSC) were compared for their immunomodulatory properties. We studied the effects of MSCs on (1) the proliferation of total lymphocytes (Ly) and on naïve T Ly subsets induced to differentiate in Th1 versus Th2 Ly; (2) the immunophenotype of different T-cell subsets; (3) and the cytokine release to verify Th1, Th2, and Th17 polarization. These were analyzed by using an in vitro co-culture system. We observed that iHPL-MSCs showed the same immunomodulatory properties observed in the FBS-MSC co-cultures. Furthermore, a more efficient effect on the increase of naïve T- cells and in the Th1 cytokine release from iHPL was observed. This study confirms that iHPL, used as a medium supplement, may be considered a good alternative to FBS for a GMP-compliant MSC expansion, and also to preserve their immunomodulatory proprieties.
