Directed Differentiation of Human Induced Pluripotent Stem Cells into Dendritic Cells Displaying Tolerogenic Properties and Resembling the CD141 Subset.

The advent of induced pluripotent stem cells (iPSCs) has begun to revolutionize cell therapy by providing a convenient source of rare cell types not normally available from patients in sufficient numbers for therapeutic purposes. In particular, the development of protocols for the differentiation of populations of leukocytes as diverse as naïve T cells, macrophages, and natural killer cells provides opportunities for their scale-up and quality control prior to administration. One population of leukocytes whose therapeutic potential has yet to be explored is the subset of conventional dendritic cells (DCs) defined by their surface expression of CD141.

Rapamycin conditioning of dendritic cells differentiated from human ES cells promotes a tolerogenic phenotype.

While human embryonic stem cells (hESCs) may one day facilitate the treatment of degenerative diseases requiring cell replacement therapy, the success of regenerative medicine is predicated on overcoming the rejection of replacement tissues. Given the role played by dendritic cells (DCs) in the establishment of immunological tolerance, we have proposed that DC, rendered tolerogenic during their differentiation from hESC, might predispose recipients to accept replacement tissues. As a first step towards this goal, we demonstrate that DC differentiated from H1 hESCs (H1-DCs) are particularly responsive to the immunosuppressive agent rapamycin compared to monocyte-derived DC (moDC).

Pharmacological manipulation of dendritic cells in the pursuit of transplantation tolerance.

Purpose Of Review: Although long-term immune suppression remains the intervention of choice for the treatment of allograft rejection, transplantation tolerance would achieve graft survival with fewer inherent risks. Although the use of dendritic cells for the induction of tolerance might confer antigen specificity, factors determining the balance between tolerogenicity and immunogenicity remain uncertain, as does the stability of the functional phenotype. Here, we review recent studies suggesting that pharmacological agents may profoundly influence this delicate balance and outline the insights they provide into parameters that contribute to the tolerogenic state.