STEM CELL TRANSPLANTATION: Edited by Marc H. Dahlke
Solid organ transplantation, together with standard-of-care immunosuppressive pharmacotherapy, is a successful therapeutic package for end-stage organ failure. With this effective treatment at hand, the new challenges in organ transplantation will now be to overcome the lack of donor organs and reduce drug-based immunosuppression to the absolutely necessary minimum. Whereas lack of donor organs is a problem of society that can only be addressed by focused and brave policy-makers, the challenge of reducing drug-based immunosuppression falls into the area of translational immunology. Cellular therapy with immunological active cells before or after organ transplantation is one of the most intriguing new ideas that have recently emerged to complement immunosuppressive pharmacotherapy. As anticipated with every novel therapeutic path, we are currently still in the ‘hype’ phase of immunomodulative cell therapy, in which many cell types and preparations are being tested in a vast array of clinical settings.
In this issue of Current Opinion in Organ Transplantation, we have asked opinion leaders in the field to summarize the most recent developments for various types of cell products. To give the reader a comprehensive overview about the current developments, the authors will introduce ‘their’ cell type, describe preclinical and clinical research in the respective areas and then outline why they believe that clinical application of their method may be better or worse than that of others. Although not truly interactive, we thus provide an interesting and very relevant debate, which will give the reader an impression of where we really stand in the translation of innovative cell therapy to the reality of solid organ transplantation.
Mesenchymal stem cells (MSCs) are bone-marrow-derived adherent progenitor cells and their translation to the clinics is already at a comparable advanced phase. Martin Hoogduijn's group from Rotterdam has contributed the review article about MSCs for this section and very neatly summarizes the most recent developments and clinical challenges. Edward Geissler's group from Regensburg focuses on human regulatory macrophages (Mregs) and outlines the advantages that this cell type has for translational application, especially in an early-phase renal transplant study. Another well described regulatory cell type is introduced by Birgit Sawitzki's group from Berlin. They contribute their experience in the field of T regulatory cell (Treg) immunology and describe clinical visions using Treg-based products. Tolerogenic dendritic cells (TolDCs) are featured by Maria-Cristina Cuturi's group from Nantes for this section. They outline risks and advantages that they see for TolDC therapies. Finally, Thomas Wekerle's team from Vienna has contributed a review article that summarizes the use of bone marrow transplantation (BMT) as a tolerogenic cell therapy for solid organ transplantation. Their article gives an overview about the first clinical experiences with this approach and highlights the most recent preclinical findings.
The possibilities for clinical explorations include MSC, Mregs, Tregs, TolDCs, BMT: it will be difficult to choose the right cell product for any given indication – not to mention that combinations of the cell populations introduced here might well be the most effective approach. To really advance this complex field beyond the ‘hype’ phase and to potentially bring useful therapies to our patients, we now need to conduct well designed, at least medium-sized, clinical trials. In the current regulatory environment and facing the development costs that result from it, this might well turn out to be an impossible task. Small case series with ‘home-made’ cell products, on the contrary, are not a good alternative. It might well be that cell therapy will be an established part of solid organ transplantation 15 years from now; it might also be that it turned out to be too complicated for routine use.
The authors is part of the MISOT initiative (http://www.misot.eu).
Conflicts of interest
There are no conflicts of interests.