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Current perspectives on mesenchymal stromal cell therapy for graft versus host disease

Cellular & Molecular Immunology 2023年第6期20卷 613-625页

作者： Nadir Kadri syivie amu llen lacobaeus Erik Boberg Katarina Le Blanc Department of Laboratory Medicine Karolinska InstitutetStockholmSweden Department of Clinical Neuroscience Division of NeurologyKarolinska Institute and Karolinska University HospitalStockholmSweden Department of Haematology Karolinska University HospitalStockholmSweden Department of Cell Therapies and Allogeneic Stem Cell Transplantation Karolinska University Hospital StockholmSweden

Graft versus host disease(GvHD)is the clinical condition in which bone marrow-derived mesenchymal stromal cells(MsCs)have been most frequently studied.In this review,we summarize the experience from clinical trials that have paved the way to translation.While MsC-based therapy has shown an exceptional safety profile,identifying potency assays and disease biomarkers that reliably predict the capacity of a specific MSC batch to alleviate GvHD has been difficult.As GvHD diagnosis and staging are based solely on clinical criteria,individual patients recruited in the same clinical trial may have vastly different underlying biology,obscuring trial outcomes and making it difficult to determine the benefit of MsCs in subgroups of patients.An accumulating body of evidence indicates the importance of considering not only the cell product but also patient-specific biomarkers and/or immune characteristics in determining MSC responsiveness.A mode of action where intravascular MSC destruction is followed by monocyte-efferocytosis-mediated skewing of the immune repertoire in a permissive inflammatory environment would both explain why cell engraftment is irrelevant for MsC efficacy and stress the importance of biologic differences between responding and nonresponding patients.We recommend a combined analysis of clinical outcomes and both biomarkers of disease activity and MSC potency assays to identify patients with GvHD who are likely to benefit from MSC therapy.

关键词： MSC GVHD Hematological malignancies acute GVHD chronic GVHD

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