Dataset Information

Multiple unit pooled umbilical cord blood is a viable source of therapeutic regulatory T cells.

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.

SUBMITTER: Milward K

PROVIDER: S-EPMC4516307 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Publications

Multiple unit pooled umbilical cord blood is a viable source of therapeutic regulatory T cells.

Milward Kate K Issa Fadi F Hester Joanna J Figueroa-Tentori Daniel D Madrigal Alejandro A Wood Kathryn J KJ

Transplantation 20130101 1

<h4>Background</h4>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.<h4>Methods</h4>In this study, we assessed the in vitro and in vivo efficacy of multiple donor ...[more]

PMID: 23263503

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Project description:ObjectiveMacrophages are multifunctional immune cells widely used in immunological research. While autologous macrophages have been widely used in several biomedical applications, allogeneic macrophages have also demonstrated similar or even superior therapeutic potential. The umbilical cord blood (UCB) is a well-described source of abundant allogenic monocytes and macrophages that is easy to collect and can be processed without invasive methods. Current monocyte isolation procedures frequently result in heterogenous cell products, with limited yields, activated cells, and high cost. This study outlines a simple isolation method that results in high yields and pure monocytes with the potential to differentiate into functional macrophages.Materials and methodsIn the experimental study, we describe a simple and efficient protocol to isolate highpurity monocytes. After collection of human UCB samples, we used a gradient-based procedure composed of three consecutive gradient steps: i. Hydroxyethyl starch-based erythrocytes sedimentation, followed by ii. Mononuclear cells (MNCs) isolation by Ficoll-Hypaque gradient, and iii. Separation of monocytes from lymphocytes by a slight hyperosmolar Percoll gradient (0.573 g/ml). Then the differentiation potential of isolated monocytes to pro- and antiinflammatory macrophages were evaluated in the presence of granulocyte colony-stimulating factor (GM-CSF) and macrophage CSF (M-CSF), respectively. The macrophages were functionally characterized as well.ResultsA high yield of monocytes after isolation (25 to 50 million) with a high purity (>95%) could be obtained from every 100-150 ml UCB. Isolated monocytes were defined based on their phenotype and surface markers expression pattern. Moreover, they possess the ability to differentiate into pro- or anti-inflammatory macrophages with specific phenotypes, gene/surface protein markers, cytokine secretion patterns, T-cell interactions, and phagocytosis activity.ConclusionHere we describe a simple and reproducible procedure for isolation of pure monocytes from UCB, which could be utilized to provide functional macrophages as a reliable and feasible source of allogenic macrophages for biomedical research.

Dataset Information

Multiple unit pooled umbilical cord blood is a viable source of therapeutic regulatory T cells.

Background

Methods

Results

Conclusion

Publications

Multiple unit pooled umbilical cord blood is a viable source of therapeutic regulatory T cells.

Similar Datasets

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