Now or never? The case for cell-based immunosuppression in kidney transplantation.
By exploiting mechanisms of immunological regulation against donor alloantigen, it may be possible to reduce the dependence of kidney transplant recipients upon calcineurin inhibitor-based maintenance immunosuppression. One means to strengthen regulatory responses is treating recipients with preparations of regulatory cells obtained by ex vivo manipulation. This strategy, which is a well-established experimental method, has been developed to the point that early-phase clinical trials in kidney transplantation are now feasible. Cell-based therapies represent a radical departure from conventional treatment, so what grounds are there for this new approach? This article offers a three-part justification for trialing cell-based therapies in kidney transplantation: first, a clinical need for alternatives to standard immunosuppression is identified, based on the inadequacies of calcineurin inhibitor-based regimens in preventing late allograft loss; second, a mechanistic explanation of how cell-based therapies might address this clinical need is given; and third, the possible benefit to patients is weighed against the potential risks of cell-based immunosuppressive therapy. It is concluded that the safety of cell-based immunosuppressive therapy will not be greatly improved by further basic scientific and preclinical development. Only trials in humans can now tell us whether cell-based therapy is likely to benefit kidney transplant recipients, but these should be conservative in design to minimize any potential harm to patients.
Department of Surgery, Section of Experimental Surgery, University Hospital Regensburg, Regensburg, Germany.
James A
JA
Hutchinson
Department of Surgery, Section of Experimental Surgery, University Hospital Regensburg, Regensburg, Germany.
Edward K
EK
Geissler
D000818:Animals; D065095:Calcineurin Inhibitors / Q000009:adverse effects; D064987:Cell- and Tissue-Based Therapy / Q000009:adverse effects; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control*; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D016030:Kidney Transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology
D065095:Calcineurin Inhibitors