4.1 Review

Update on mesenchymal stromal cell studies in organ transplant recipients

Journal

CURRENT OPINION IN ORGAN TRANSPLANTATION
Volume 25, Issue 1, Pages 27-34

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MOT.0000000000000716

Keywords

mesenchymal stromal cells; regulatory T cells; solid organ transplantation; tolerance

Funding

  1. Fondazione ART per la Ricerca sui Trapianti (Milan, Italy)
  2. Fondazione Aiuti per la Ricerca sulle Malattie Rare (ARMR, Bergamo, Italy)

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Purpose of review Mesenchymal stromal cells (MSC) have been proposed as a novel cell therapy for immune-mediated diseases, including solid organ transplantation. Here, we provide an overview of recent preclinical and clinical studies in solid organ transplantation using MSC immunomodulatory therapy. Recent findings MSC have been tested successfully in models of corneal and lung transplantation, suggesting that either the programmed cell death protein 1/programmed death ligand 1 pathway or the generation of intermediary immune-regulatory monocyte-macrophage population are the main mechanisms of the protolerogenic effect of MSC. In clinical transplantation, allogeneic MSC from bone marrow or umbilical cord have been evaluated in kidney and lung transplantation with an excellent safety profile. Recent data from kidney transplant patients given autologous bone marrow-MSC enrolled in our phase 1 study demonstrated a good long term safety profile. Extensive immunomonitoring of this initial cohort provided evidence of the development of a protolerogenic environment in some MSC-treated patients. One of these patients has been weaned off immunosuppression successfully. The available clinical studies in kidney, liver and lung transplantation indicate that autologous and allogeneic MSC therapy from different sources are safe. Now it's time to focus on well-designed efficacy clinical trials, possibly including extensive immunomonitoring.

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