title: Mesenchymal stromal cells in renal transplantation: opportunities and challenges.
abstract: Lifelong immunosuppressive therapy is essential to prevent allograft rejection in transplant recipients. Long-term, nonspecific immunosuppression can, however, result in life-threatening complications and fail to prevent chronic graft rejection. Bone marrow (BM)-derived multipotent mesenchymal stromal cells (MSCs) have emerged as a potential candidate for cell-based therapy to modulate the immune response in organ transplantation. These cells can repair tissue after injury and downregulate many of the effector functions of immune cells that participate in the alloimmune response, converting them into regulatory cells. The findings of preclinical and initial clinical studies support the potential tolerance-inducing effects of MSCs and highlight the unanticipated complexity of MSC therapy in kidney transplantation. In animal models of transplantation MSCs promote donor-specific tolerance through the generation of regulatory T cells and antigen-presenting cells. In some settings, however, MSCs can acquire proinflammatory properties and contribute to allograft dysfunction. The available data from small clinical studies suggest that cell infusion is safe and well tolerated by kidney transplant recipients. Ongoing and future trials will provide evidence regarding the long-term safety of MSC therapy and determine the optimum cell source (either autologous or allogeneic) and infusion protocol to achieve operational tolerance in kidney transplant recipients. These studies will also provide additional evidence regarding the risks and benefits of MSC infusion and will hopefully offer definitive answers to the important questions of when, where, how many and which types of MSCs should be infused to fully exploit their immunomodulatory, pro-tolerogenic and tissue-repairing properties.
authors: IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Transplant Research Center "Chiara Cucchi de Alessandri e Gilberto Crespi", Via G.B. Camozzi 3, 24020 Ranica, Bergamo, Italy.
authors: Federica
authors: F
authors: Casiraghi
authors: IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Clinical Research Center for Rare Diseases "Aldo &Cele Daccò", Via G.B. Camozzi 3, 24020 Ranica, Bergamo, Italy.
authors: Norberto
authors: N
authors: Perico
authors: IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Transplant Research Center "Chiara Cucchi de Alessandri e Gilberto Crespi", Via G.B. Camozzi 3, 24020 Ranica, Bergamo, Italy.
authors: Monica
authors: M
authors: Cortinovis
authors: IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Clinical Research Center for Rare Diseases "Aldo &Cele Daccò", Via G.B. Camozzi 3, 24020 Ranica, Bergamo, Italy.
authors: Giuseppe
authors: G
authors: Remuzzi
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000601:surgery*; D016030:Kidney Transplantation / Q000379:methods*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D023001:Transplantation Tolerance / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents