Vascular Cells and Tissue Constructs Derived from Human Pluripotent Stem Cells for Toxicological Screening

Area of Science:

• Regenerative Medicine
• Toxicology
• Drug Development

Background:

• Human pluripotent stem cells (hPSCs) offer a renewable source for generating various somatic cell types.
• Traditional toxicological testing relies on animal models or primary cells, which have limitations in predictability and variability.
• Developing human-based in vitro models is crucial for accurate chemical toxicity and drug efficacy assessment.

Purpose of the Study:

• To generate vascular cell populations from hPSCs for use in toxicological screening.
• To develop 3D co-culture models using hPSC-derived vascular cells that self-organize into microvasculature-like structures.
• To evaluate the utility of these hPSC-derived vascular constructs for high-throughput screening of chemical agents.

Main Methods:

• Generation of smooth muscle cells and endothelial cells from hPSCs.
• Assembly of hPSC-derived vascular cells into 3D co-cultures within supportive gel matrices.
• High-throughput screening of environmental and clinical chemical agents using the developed vascular constructs.
• Assessment of immunological and toxicological responses to screened chemicals.

Main Results:

• Successful generation of vascular cell populations and self-organized 3D co-cultures resembling microvasculature.
• Effective stratification of screened chemicals based on toxicity levels.
• Observation of both cell type-specific and co-culture-dependent toxicological responses.
• Demonstration of the utility of hPSC-derived vascular models in identifying chemical toxicity.

Conclusions:

• hPSC-derived vascular cells and their 3D co-cultured constructs are suitable for toxicological and drug screening applications.
• These models provide a human-based in vitro system that can potentially replace or reduce reliance on animal models.
• Further development of these hPSC-derived vascular systems holds promise for advancing preclinical drug development and chemical safety assessment.