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Preparation and Gene Modification of Nonhuman Primate Hematopoietic Stem and Progenitor Cells
Published on: February 15, 2019
Nonhuman Primates and Translational Research-Cardiovascular Disease
Laura A Cox1,2, Michael Olivier1,2, Kimberly Spradling-Reeves1
1Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas.
Insights
Nonhuman primates (NHPs) offer valuable models for studying cardiovascular disease (CVD) due to their human-like physiology and accelerated aging. NHPs help uncover genetic and environmental factors influencing CVD initiation and progression.
Area of Science:
- Comparative Medicine
- Cardiovascular Research
- Primate Models
Background:
- Cardiovascular disease (CVD) is a leading cause of death in the US, but human studies face challenges due to environmental variability.
- Nonhuman primates (NHPs) share significant genetic, metabolic, and physiological similarities with humans, making them suitable models for CVD research.
- NHPs exhibit natural development of CVD and accelerated aging-related comorbidities, offering unique advantages over traditional animal models.
Purpose of the Study:
- To review current CVD research in Old World NHPs, focusing on areas where nonprimate models have limitations.
- To highlight the strengths of various NHP species in modeling human CVD mechanisms, including genetics, epigenetics, and environmental interactions.
- To explore NHP models for understanding specific CVD aspects like metabolic syndrome, nonalcoholic fatty liver disease, and the role of the microbiome.
Main Methods:
- Review of existing literature on cardiovascular disease research in Old World nonhuman primate species.
- Focus on studies investigating genetic, epigenetic, and environmental factors (e.g., diet, calorie restriction, obesity) in CVD development.
- Inclusion of research on age-related comorbidities, nonalcoholic steatohepatitis, Chagas disease, microbiome, and stem cell applications in CVD.
Main Results:
- NHPs naturally develop CVD without genetic manipulation, providing models to identify genetic variants influencing disease risk.
- NHP models allow for controlled studies of gene-environment interactions, crucial for understanding complex diseases like CVD.
- Age-related comorbidities such as dyslipidemia and diabetes manifest 3-4 times faster in NHPs than in humans, accelerating research timelines.
Conclusions:
- Old World NHPs are powerful models for elucidating the mechanisms underlying human cardiovascular disease initiation and progression.
- NHP research facilitates the study of genetic predispositions, epigenetic modifications, and the impact of lifestyle factors on CVD.
- These models offer critical insights into complex conditions like metabolic syndrome and nonalcoholic steatohepatitis, aiding in CVD prevention strategies.
Abstract:
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States. Human epidemiological studies provide challenges for understanding mechanisms that regulate initiation and progression of CVD due to variation in lifestyle, diet, and other environmental factors. Studies describing metabolic and physiologic aspects of CVD, and those investigating genetic and epigenetic mechanisms influencing CVD initiation and progression, have been conducted in multiple Old World nonhuman primate (NHP) species. Major advantages of NHPs as models for understanding CVD are their genetic, metabolic, and physiologic similarities with humans, and the ability to control diet, environment, and breeding. These NHP species are also genetically and phenotypically heterogeneous, providing opportunities to study gene by environment interactions that are not feasible in inbred animal models. Each Old World NHP species included in this review brings unique strengths as models to better understand human CVD. All develop CVD without genetic manipulation providing multiple models to discover genetic variants that influence CVD risk. In addition, as each of these NHP species age, their age-related comorbidities such as dyslipidemia and diabetes are accelerated proportionally 3 to 4 times faster than in humans.In this review, we discuss current CVD-related research in NHPs focusing on selected aspects of CVD for which nonprimate model organism studies have left gaps in our understanding of human disease. We include studies on current knowledge of genetics, epigenetics, calorie restriction, maternal calorie restriction and offspring health, maternal obesity and offspring health, nonalcoholic steatohepatitis and steatosis, Chagas disease, microbiome, stem cells, and prevention of CVD.
