Milward, K; Issa, F; Hester, J; Figueroa-Tentori, D; Madrigal, A; Wood, K; (2013) Multiple Unit Pooled Umbilical Cord Blood is a Viable Source of Therapeutic Regulatory T Cells. Transplantation , 15 (95) , Article 1. 10.1097/TP.0b013e31827722ed.

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Abstract

BACKGROUND: Regulatory T cells (Treg) are potentially a useful therapeutic option for the treatment of immunopathological conditions including graft-versus-host disease. Umbilical cord blood (UCB) offers certain advantages over adult peripheral blood (APB) as a source of Treg for cellular therapy but yields far fewer Treg per unit. Pooling of Treg from multiple donors may overcome this challenge. METHODS: In this study, we assessed the in vitro and in vivo efficacy of multiple donor pooled UCB or APB-derived Treg. RESULTS: In vitro, pooled freshly isolated UCB-derived Treg were as suppressive as APB-derived Treg. However, in a mouse model of human skin allodestruction, pooled UCB-derived Treg were more potent at suppressing alloresponses and prolonging skin survival compared with pooled APB-derived Treg. Improved survival of UCB Treg in an in vivo cell survival assay and their lower expression of human leukocyte antigen-ABC suggested that lower immunogenicity may account for their superior efficacy in vivo. CONCLUSION: Multiple-unit UCB is therefore a viable source of human Treg for cellular therapy, and pooling of Treg from multiple donors offers a useful strategy for achieving required therapeutic doses.

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