Cellular Therapies in Solid Organ Allotransplantation: Promise and Pitfalls

Abstract

Donor specific transfusions have been the basis of tolerance inducing protocols since Peter Medawar showed that it was experimentally feasible in the 1950s. Though trials of cellular therapies have become increasingly common in solid organ transplantation, they have not become standard practice. Additionally, whereas some protocols have focused on cellular therapies as a method for donor antigen delivery-thought to promote tolerance in and of itself in the correct immunologic context-other approaches have alternatively focused on the intrinsic immunosuppressive properties of the certain cell types with less emphasis on their origin, including mesenchymal stem cells, regulatory T cells, and regulatory dendritic cells. Regardless of intent, all cellular therapies must contend with the potential that introducing donor antigen in a new context will lead to sensitization. In this review, we focus on the variety of cellular therapies that have been applied in human trials and non-human primate models, describe their efficacy, highlight data regarding their potential for sensitization, and discuss opportunities for cellular therapies within our current understanding of the immune landscape.

Keywords: allosensitization; allotransplantation; donor specific antibodies; donor specific transfusion (DST); mesenchymal stem cell; sensitization; tolerance.

Figure 1

Cellular therapies in transplantation can be broadly categorized into five groups: donor specific transfusions (DSTs), hematopoietic stem cell transplant (HSCT), mesenchymal stem cell based therapy (MSC), manufactured immune cell therapy (using various regulatory cells), and modified immune cell (MIC) therapy. These broad categories can be further subdivided by the source of the cells. Whereas recipient derived cells carry no risk of sensitization (or very little), donor derived cells inherently may sensitize the recipient. Additionally, 3^rd party cells, depending on their genetic similarity with donor and recipient, may or may not be sensitizing. When evaluating cellular therapies, both the function and origin of cells are of import.