Abstract

Engineering functional durable engineered blood vessels from human induced pluripotent stem cells

Rekha Samuel, Professor, Christian Medical College

Critical challenges of human induced pluripotent stem (hiPS) cell-based regenerative medicine is the efficient generation of potent vasculogenic cells and biologically relevant systems to assess functionality of engineered vessels in vivo. Methods: We derived endothelial precursor cells from hiPS cells using a triple selection of markers: CD34, neuropilin-1 (NP-1) and KDR, and an efficient 2-D culture system. Non-invasive Multiphoton Laser Scanning Microscopy determined functionality of blood vessels in vivo in cranial window models of SCID mice. Results: hiPS -derived blood vessels obtained from healthy donors lasted for 280 days in vivo in SCID mice. The RBC velocities of engineered blood vessels were comparable to normal endogenous host vessels (1.36+/- 0.3mm/s), and demonstrated a higher permeability as compared to endogenous vessels. We generated mesenchymal precursor cells from hiPS cells that were comparable with human bone marrow derived mesenchymal stem cells. Using endothelial cells and mesenchymal precursor cells derived from the same hiPS cell line we generated functional blood vessels in vivo. The durability of hiPS-derived blood vessels in vivo demonstrates a potential translation of this approach in long-term vascularization for tissue engineering and treatment of vascular diseases. Finally, hiPS-derived vasculogenic cells are important to examine vascular defects ‘in a dish’.