Cardiovascular disorders have been the predominant cause of mortality on a global level. It has urged the scientists to develop new treatment procedures and therapeutics. However, it requires understanding of cardiac cellular pathways and its genotype. Moreover, the evaluation of the safety and efficacy of the drugs necessitates an appropriate in vitro and in vivo model. Pigs are almost 98% identical to humans and are already employed for in vivo research. Therefore, the employment of primary swine or porcine cardiomyocytes from pig for in vitro studies has clinical relevance in cardiac research.

Why Primary Swine Cardiomyocytes?

Cardiomyocytes are the muscle cells present in the heart and are responsible for its contraction. Human cardiac muscle cells are the most appropriate in vitro model for cardiovascular research. However, isolation of cardiac tissue from humans has limited availability. Cardiomyocytes developed from induced pluripotent stem cells have been employed. But they are immature and differ from adult human cells in structural and functional aspects. Another feasible option is swine cardiomyocytes.

Human and pig hearts bear resemblance in hemodynamic, structural, electrophysiological, and size-based characteristics, prompting the use of porcine cardiomyocytes in preclinical research. Cardiac features such as heart rate and contractility are extensively studied in research and are comparable between humans and pigs. The genetic profiles of human and pig cardiac muscle cells are also similar. These parallels between human and pig hearts have prompted the use of primary porcine cardiomyocytes as an in vitro model for cardiovascular research.

Culture of Primary Swine Cardiomyocytes

The primary porcine cardiomyocytes have generated interest in outlining their isolation and culture process. The perfusion method with Langendorff apparatus and the following enzymatic digestion is used for isolation of the cells. The culture of primary cells aims to maintain a homogenous cell population for the long-term. Their culture media comprise a basal medium of either DMEM and F-12 or M-199. Initially, cells show negligible attachment to the substrate in the serum-based medium. Lack of attachment caused them to assume a rounded morphology. However, they transformed to their original shape as they adhered to the substrate. This culture method was termed the redifferentiation. Furthermore, attachment to the substrate didn’t require serum in the media. This culture method is the rapid attachment method. It served as a better method for retaining the morphology and functions of cardiac muscle cells. The medium also requires additional supplementation with epidermal growth factor (EGF).

Role of Primary Swine Cardiomyocytes in Cardiovascular Research

With the rising burden of cardiovascular disorders, the research into cardiac tissue structure and function has increased. The porcine cardiomyocytes have found applications in cardiovascular research owing to their abundance and cost-effectiveness. Researchers can investigate the underlying signaling mechanisms behind the electrophysiological and muscular activity of cardiac tissue. It has prompted the development of new therapeutic interventions. Scientists have also genetically engineered these cells to facilitate their xenotransplantation. Experimenting on them has provided insights into the development and regeneration of the heart. It has aided in the development of treatments to repair cardiac injury. The efficacy of these drugs could be evaluated on these cells for their effectiveness. Primary porcine cells have the potential to form 3D models that can imitate the in vivo environment of the organ.

Applications of Primary Swine Cardiomyocytes in Drug Development

The pharmaceutical research focuses on the formulation of new medications and improving the already existing drugs with regard to reducing their cost and off-target effects. The cardiac issues have various comorbidities. Frequently the therapeutics used as standard treatment of care, such as kinase inhibitors, antibiotics, antidepressants, etc., also exhibit cardiotoxic effects. Several drugs have been withdrawn from the market for causing cardiac issues. It has urged the researchers to perform toxicological screening of the newly developed drugs on cardiomyocytes. But toxicity screening was performed on kidney cell lines. However, they lack the various ion channels and the signaling pathways that are an integral part of the human heart. The evaluation of drugs on kidney cell lines even resulted in removal of drugs during the clinical trial stage due to false toxicity issues. Primary porcine cardiac cells are more suitable for screening drugs for triggering cardiac-related toxic effects.

Conclusion

The growing cases of cardiovascular disorders have encouraged the scientific community to devise therapeutic alternatives. Every new-age therapeutic undergoes rigorous testing in animal models. Small animal models, especially rodents differ in their heart rate, life span, surface-to-body ratio, and genetic profile from the human heart. For cardiovascular research, pigs are the suitable model since porcine heart share similarities with that of the human heart. Additionally, they are easily available and are cost-effective. These cells are also suitable for toxicity assessment of non-cardiac-related drugs. Scientists have gained significant insights from in vitro research on primary porcine cardiomyocytes. They have wide applications in basic, pharmacological, and toxicological research. Therefore, they would be beneficial for research into cardiac tissue. Kosheeka delivers high-quality cardiomyocytes from the ventricle of adult porcine heart at passage 2.