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Nonhuman primate transplant models finally evolve: detailed immunogenetic analysis creates new models and strengthens the old.

ABSTRACT: Nonhuman primate (NHP) models play a critical role in the translation of novel therapies for transplantation to the clinic. However, although MHC disparity significantly affects the outcome of transplantation, until recently, experiments using NHP models were performed without the ability to rigorously control the degree of MHC disparity in transplant cohorts. In this review, we discuss several key technical breakthroughs in the field, which have finally enabled detailed immunogenetic data to be incorporated into NHP transplantation studies. These advances have created a new gold-standard for NHP transplantation research, which incorporates detailed information regarding the degree of relatedness and the degree of MHC haplotype disparity between transplant pairs and the precise MHC alleles that both donors and recipients express. The adoption of this new standard promises to increase the rigor of NHP transplantation studies and to ensure that these experiments are optimally translatable to patient care.

SUBMITTER: Kean LS

PROVIDER: S-EPMC3482466 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Nonhuman primate transplant models finally evolve: detailed immunogenetic analysis creates new models and strengthens the old.

Kean L S LS Singh K K Blazar B R BR Larsen C P CP

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 20111217 4

Nonhuman primate (NHP) models play a critical role in the translation of novel therapies for transplantation to the clinic. However, although MHC disparity significantly affects the outcome of transplantation, until recently, experiments using NHP models were performed without the ability to rigorously control the degree of MHC disparity in transplant cohorts. In this review, we discuss several key technical breakthroughs in the field, which have finally enabled detailed immunogenetic data to be ...[more]

PMID: 22177005

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Project description:Parthenogenesis is the biological phenomenon by which embryonic development is initiated without male contribution. Whereas parthenogenesis is a common mode of reproduction in lower organisms, the mammalian parthenote fails to produce a successful pregnancy. We herein describe in vitro parthenogenetic development of monkey (Macaca fascicularis) eggs to the blastocyst stage, and their use to create a pluripotent line of stem cells. These monkey stem cells (Cyno-1 cells) are positive for telomerase activity and are immunoreactive for alkaline phosphatase, octamer-binding transcription factor 4 (Oct-4), stage-specific embryonic antigen 4 (SSEA-4), tumor rejection antigen 1-60 (TRA 1-60), and tumor rejection antigen 1-81 (TRA 1-81) (traditional markers of human embryonic stem cells). They have a normal chromosome karyotype (40 + 2) and can be maintained in vitro in an undifferentiated state for extended periods of time. Cyno-1 cells can be differentiated in vitro into dopaminergic and serotonergic neurons, contractile cardiomyocyte-like cells, smooth muscle, ciliated epithelia, and adipocytes. When Cyno-1 cells were injected into severe combined immunodeficient mice, teratomas with derivatives from all three embryonic germ layers were obtained. When grown on fibronectin/laminin-coated plates and in neural progenitor medium, Cyno-1 cells assume a neural precursor phenotype (immunoreactive for nestin). However, these cells remain proliferative and express no functional ion channels. When transferred to differentiation conditions, the nestin-positive precursors assume neuronal and epithelial morphologies. Over time, these cells acquire electrophysiological characteristics of functional neurons (appearance of tetrodotoxin-sensitive, voltage-dependent sodium channels). These results suggest that stem cells derived from the parthenogenetically activated nonhuman primate egg provide a potential source for autologous cell therapy in the female and bypass the need for creating a competent embryo.

Dataset Information

Nonhuman primate transplant models finally evolve: detailed immunogenetic analysis creates new models and strengthens the old.

Publications

Nonhuman primate transplant models finally evolve: detailed immunogenetic analysis creates new models and strengthens the old.

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