Nonhuman Primate Models in Translational Regenerative Medicine

Daadi, Marcel M.; Barberi, Tiziano; Shi, Qiang; Lanford, Robert E.

doi:10.1089/scd.2014.0374

Cited by 19 publications

(14 citation statements)

References 30 publications

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“…Nonhuman primates are distinct from other large-animal models because these animals are phylogenetically closer to humans and their immune system has been well studied in translational medicine 209 . These features give nonhuman primate models an important role in studies of allogeneic stem cell transplantation, which is considered to be one of the main therapeutic approaches for heart regeneration 210 .…”

Section: Fig 1 |mentioning

confidence: 99%

Therapeutic approaches for cardiac regeneration and repair

2018

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Ischaemic heart disease is a leading cause of death worldwide. Injury to the heart is followed by loss of the damaged cardiomyocytes, which are replaced with fibrotic scar tissue. Depletion of cardiomyocytes results in decreased cardiac contraction, which leads to pathological cardiac dilatation, additional cardiomyocyte loss, and mechanical dysfunction, culminating in heart failure. This sequential reaction is defined as cardiac remodelling. Many therapies have focused on preventing the progressive process of cardiac remodelling to heart failure. However, after patients have developed end-stage heart failure, intervention is limited to heart transplantation. One of the main reasons for the dramatic injurious effect of cardiomyocyte loss is that the adult human heart has minimal regenerative capacity. In the past 2 decades, several strategies to repair the injured heart and improve heart function have been pursued, including cellular and noncellular therapies. In this Review, we discuss current therapeutic approaches for cardiac repair and regeneration, describing outcomes, limitations, and future prospects of preclinical and clinical trials of heart regeneration. Substantial progress has been made towards understanding the cellular and molecular mechanisms regulating heart regeneration, offering the potential to control cardiac remodelling and redirect the adult heart to a regenerative state.

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Section: Fig 1 |mentioning

confidence: 99%

Therapeutic approaches for cardiac regeneration and repair

2018

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“…NHPs mimic humans in many ways including similarities in genome, neuroanatomy, neurophysiology, immunogenetics, and age-related changes in immune function [ 3 , 4 ]. NHPs also share similar hematopoietic stem cell dynamics, engraftment properties, and cytokine requirements with humans [ 5 , 6 ]. Studies of the genome of Macaca mulatta have revealed 93% sequence similarity between M .…”

Section: Introductionmentioning

confidence: 99%

Whole thorax irradiation of non-human primates induces persistent nuclear damage and gene expression changes in peripheral blood cells

et al. 2018

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We investigated the cytogenetic and gene expression responses of peripheral blood cells of non-human primates (NHP, Macaca mulatta) that were whole-thorax irradiated with a single dose of 10 Gy. In this model, partial irradiation of NHPs in the thoracic region (Whole Thorax Lung Irradiation, WTLI) allows the study of late radiation-induced lung injury, while avoiding acute radiation syndromes related to hematopoietic and gastrointestinal injury. A transient drop in circulating lymphocytes and platelets was seen by 9 days, followed by elevations in respiratory rate, circulating neutrophils, lymphocytes, and monocytes at 60–100 days, corresponding to computed tomography (CT) and histologic evidence of pneumonitis, and elective euthanasia of four animals. To evaluate long-term DNA damage in NHP peripheral blood lymphocytes after 10 Gy WTLI, we used the cytokinesis-block micronucleus (CBMN) assay to measure chromosomal aberrations as post-mitotic micronuclei in blood samples collected up to 8 months after irradiation. Regression analysis showed significant induction of micronuclei in NHP blood cells that persisted with a gradual decline over the 8-month study period, suggesting long-term DNA damage in blood lymphocytes after WTLI.We also report transcriptomic changes in blood up to 30 days after WTLI. We isolated total RNA from peripheral blood at 3 days before and then at 2, 5 and 30 days after irradiation. We identified 1187 transcripts that were significantly changed across the 30-day time course. From changes in gene expression, we identified biological processes related to immune responses, which persisted across the 30-day study. Response to oxygen-containing compounds and bacteria were implicated by gene-expression changes at the earliest day 2 and latest, day 30 time-points. Gene expression changes suggest a persistent altered state of the immune system, specifically response to infection, for at least a month after WTLI.

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“…Although non-human primates (NH-primates) represent only a small share of the animals used in medical research, the significance of those studies for human health, especially pharmaceuticals and new therapeutic approaches, is prominent [3,4]. NH-primates are often the most suitable model for assessing the safety and efficiency of said drugs prior to human trials [5] and supply information to connect data from other relevant clinical models, such as rodents, to humans [6].…”

Section: Introductionmentioning

confidence: 99%

Induced Pluripotent Stem Cells from Animal Models: Applications on Translational Research

Pessôa¹,

Pieri²,

Recchia³

et al. 2021

Novel Perspectives of Stem Cell Manufacturing and Therapies

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Over the history of humankind, knowledge acquisition regarding the human body, health, and the development of new biomedical techniques have run through some animal model at some level. The mouse model has been primarily used as the role model for a long time; however, it is severely hampered regarding its feasibility for translational outcomes, in particular, to preclinical and clinical studies. Herein we aim to discuss how induced pluripotent stem cells generated from non-human primates, pigs and dogs, all well-known as adequate large biomedical models, associated or not with gene editing tools, can be used as models on in vivo or in vitro translational research, specifically on regenerative medicine, drug screening, and stem cell therapy.

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Nonhuman Primate Models in Translational Regenerative Medicine

Cited by 19 publications

References 30 publications

Therapeutic approaches for cardiac regeneration and repair

Therapeutic approaches for cardiac regeneration and repair

Whole thorax irradiation of non-human primates induces persistent nuclear damage and gene expression changes in peripheral blood cells

Induced Pluripotent Stem Cells from Animal Models: Applications on Translational Research

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