Pig Stem Cells May Enhance Cardiovascular Tissue Engineering

This study focused on creating pig stem cells that do not have any added genes, known as transgene-free pig induced pluripotent stem cells. These cells can transform into various cell types, including vascular endothelial cells, which line the interior surface of blood vessels. The researchers aimed to see if these stem cells could produce functional endothelial cells that could be used in engineered blood vessels, known as tissue-engineered vascular conduits. This advancement could contribute to modeling new treatments for heart and blood vessel diseases.

Cardiovascular diseases are a leading cause of death globally, making the development of effective treatments vital. Pigs are valuable models for cardiovascular research due to their similarities to humans. However, the absence of suitable pig induced pluripotent stem cells has hindered progress. By creating transgene-free pig induced pluripotent stem cells, this study enhances the quality of models for preclinical testing of stem cell therapies. This advancement potentially speeds up the development of new treatments for heart and blood vessel diseases, leading to significant advances in heart disease treatment.

The researchers generated transgene-free pig induced pluripotent stem cells by reprogramming pig cells with a virus-based method. They optimized the culture conditions to guide the differentiation of the pig induced pluripotent stem cells into endothelial cells. These cells were then used to create tissue-engineered vascular conduits, which were tested in rats to evaluate their functionality and effectiveness in preventing blood clots.

The study successfully produced transgene-free pig induced pluripotent stem cells that could differentiate into endothelial cells with characteristics similar to natural pig endothelial cells. These cells, when used in tissue-engineered vascular conduits, maintained important endothelial markers and prevented blood clotting in rats. This confirmed their potential for preclinical modeling of cardiovascular tissue engineered therapies.

Creating functional endothelial cells from transgene-free pig induced pluripotent stem cells offers new possibilities for cardiovascular research and therapy development. These cells can improve animal models for testing the safety and efficacy of new treatments, potentially speeding up the transition of stem cell-based therapies from the laboratory to clinical use.

The researchers recommend additional testing of pig induced pluripotent stem cell-derived endothelial cells in larger animal models, such as pigs, to better replicate human heart and blood vessel conditions. They also suggest exploring the use of these cells in various tissue-engineered applications to assess their broader potential in regenerative medicine. Future research may involve developing pig stem cells that are less likely to be rejected by the immune system for more widespread therapeutic use.

The study reported significant fold changes in gene expression using qRT-PCR, with SV1-piPSCs showing a 300-fold increase in pig OCT4 expression compared to DOX-piPSCs. Statistical tests included one-way ANOVA with Tukey multiple comparisons and two-tailed unpaired Student's t-tests, with p-values < 0.05 deemed significant. TEVCs demonstrated significant upregulation of EC maturation markers under shear stress, marked by p-values < 0.0001. These results indicate robust endothelial cell differentiation and functionality.

This research was supported by the National Institutes of Health (awards R01HL116705, R01HL155411, R01HL150352, R01HL171984, F31HL149289, and 3R01HL150352-03S2). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The research also received support from the Department of Defense, the Gruber Science Fellowship at Yale, and Yale University.