Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Comparative genomic analysis of human and non-human primate CD34+ MPBSCs exposed to PGE2

ABSTRACT: Abstract: Hematopoietic stem cells (HSCs) are used in transplantation therapy to reconstitute the hematopoietic system. Human cord blood (hCB) transplantation has emerged as an attractive alternative treatment option when traditional HSC sources are unavailable, however, the absolute number of hCB HSCs transplanted is significantly lower than bone marrow or mobilized peripheral blood stem cells (MPBSCs). We previously demonstrated that dimethyl-prostaglandin E2 (dmPGE2) increased HSCs in vertebrate models. Here, we describe preclinical analyses of the therapeutic potential of dmPGE2-treatment using human and non-human primate HSCs. dmPGE2 significantly increased total human hematopoietic colony formation in vitro and enhanced engraftment of unfractionated and CD34+ hCB following xenotransplantation. In non-human primate autologous transplantation, dmPGE2-treated CD34+ MPBSCs showed stable multilineage engraftment over one year post-infusion. Together, our analyses indicated that dmPGE2 mediates conserved responses in HSCs from human and non-human primates, and provided sufficient preclinical information to support proceeding to an FDA-approved phase 1 clinical trial. In order to identify the potential mechanism of action of dmPGE2 on gene expression and HSC function, and to possibly explain the muted response of rhesus CD34+ MPBSCs to dmPGE2 exposure, microarray gene expression analysis was conducted. Human and rhesus CD34+ MPBSCs were exposed to DMSO control or dmPGE2 at a dose of either 10 and 50 uM as described above, and processed for microarray analysis at 0, 2, 6, 12 and 24 hours post treatment. Four human donors contributed 8 to 10 samples each at varying time points and dosage for a total of 37 samples (2 samples were technical repeats). Six rhesus macaques contributed 3 to 9 samples each at varying time points and dosage for a total of 28 samples (4 samples were technical repeats). Pooled PBMC's from 6 donors aphereses were used as a reference sample.

ORGANISM(S): Macaca mulatta

SUBMITTER: Francesco Marincola

PROVIDER: E-GEOD-27126 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Prostaglandin E2 enhances human cord blood stem cell xenotransplants and shows long-term safety in preclinical nonhuman primate transplant models.

Goessling Wolfram W Allen Robyn S RS Guan Xiao X Jin Ping P Uchida Naoya N Dovey Michael M Harris James M JM Metzger Mark E ME Bonifacino Aylin C AC Stroncek David D Stegner Joseph J Armant Myriam M Schlaeger Thorsten T Tisdale John F JF Zon Leonard I LI Donahue Robert E RE North Trista E TE

Cell stem cell 20110401 4

Hematopoietic stem cells (HSCs) are used in transplantation therapy to reconstitute the hematopoietic system. Human cord blood (hCB) transplantation has emerged as an attractive alternative treatment option when traditional HSC sources are unavailable; however, the absolute number of hCB HSCs transplanted is significantly lower than bone marrow or mobilized peripheral blood stem cells (MPBSCs). We previously demonstrated that dimethyl-prostaglandin E2 (dmPGE2) increased HSCs in vertebrate models ...[more]

PMID: 21474107

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Dataset Information

Comparative genomic analysis of human and non-human primate CD34+ MPBSCs exposed to PGE2

Publications

Prostaglandin E2 enhances human cord blood stem cell xenotransplants and shows long-term safety in preclinical nonhuman primate transplant models.

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