Abstract 18759: Vascular Smooth Muscle Cells Derived From Inbred Swine Induced Pluripotent Stem Cells for Vascular Tissue Engineering
Introduction: Development of autologous tissue-engineered vascular constructs using vascular smooth muscle cells (VSMCs) derived from human induced pluripotent stem cells (hiPSCs) holds great potential in treating patients with vascular defects. However, preclinical, large animal iPSC-based cellular and tissue models are required to evaluate the safety and efficacy prior to clinical application of hiPSC-based therapies.
Hypothesis: Continual expression of ectopic reprogramming factors blocks efficient lineage differentiation and VSMC derivation, and vascular tissue can be readily engineered from swine iPSC (siPSC)-derived VSMCs.
Methods: Doxycycline-inducible reprogramming factors were introduced into fetal fibroblasts from inbred Massachusetts General Hospital (MGH) miniature swine that receive heart grafts without immunosuppression within the colony. A novel and highly efficient embryoid body (EB)-based approach was used to differentiate siPSCs into functional VSMCs. Vascular tissues were engineered from siPSC-VSMCs with biodegradable polyglycolic acid (PGA) scaffolds as well as scaffold-free, self-assembly approach.
Results: Herein, siPSC lines were successfully established from inbred MGH miniature swine fetal fibroblasts. Highly enriched, functional VSMCs were derived from siPSCs based on the addition of ascorbic acid and the inactivation of reprogramming factor via doxycycline withdrawal. Moreover, siPSC-VSMCs seeded onto biodegradable PGA scaffolds readily formed vascular tissues, which were implanted subcutaneously into immunodeficient mice and showed further maturation revealed by expression of mature marker smooth muscle myosin heavy chain (SMMHC). Finally, using a robust cellular self-assembly approach, we developed 3D tissue rings from siPSC-VSMCs that showed comparable mechanical properties to those from swine primary VSMCs.
Conclusions: Our studies represent the development of the first engineered vascular constructs based on inbred siPSCs, and offer great opportunities for preclinical investigation of autologous hiPSC-based vascular tissues for patient treatment.
Author Disclosures: Y. Qyang: None. J. Luo: None. L. Qin: None. M. Kural: None. D. Kotton: None. R. Hawley: None. D.H. Sachs: None. L. Niklason: None.
- © 2016 by American Heart Association, Inc.