Autologous Vascular Regeneration for Peripheral Artery Disease Patients

Project: Research project

Project Details

Description

The clinical translation of stem cell-based therapies for the treatment of peripheral artery disease (PAD) is currently hindered by the lack of a defined cell source, unoptimized delivery strategies, and unknown fate of administered cells. The advent of induced pluripotent stem cells (iPSCs) offers an exceptional opportunity for regenerating functional tissues for various diseases, including PAD. Nuclear imaging techniques together with reporter gene transgenic expression provide a highly sensitive, non-invasive tool to monitor the fate of viable transplanted cells in vivo. Furthermore, advanced functional biomaterial scaffolds that can deliver stem cells to the targeted tissues/organs and promote stem cell survival, differentiation and integration to host tissues may potentially transform the clinical outcome of stem-cell based regenerative therapies. The objective of this study is to manufacture clinical-grade autologous iPSC derived vascular endothelial cells (iPSC-ECs) as an autologous cell source for PAD patient vascular regeneration, demonstrate non-invasive cell tracking in vivo using a clinical-applicable non-invasive imaging technique, and enable long-term cell survival as key milestones for vascular regenerative medicine. The hypotheses are: (1) the biodistribution and long-term survival of iPSC-ECs expressing human sodium iodide symporter (hNIS) can be tracked non-invasively in vivo Single Photon Emission Computed Tomography /Computed Tomography (SPECT/CT) without affecting EC functions; and (2) an antioxidant cell engraftment niche that promotes cell adhesion and spreading of iPSC-ECs and supporting vascular cells will reduce oxidative cell damage, improve cell engraftment and survival rate, and support limb revascularization. This study is essential to help establish optimized cell manufacturing protocols, develop cell preservation agents for limb revascularization, and develop cell tracking procedures to offer additional treatment options for PAD patients. The specific aims are 1. Manufacture clinical-grade autologous and trackable iPSC-ECs for patients with PAD in a cGMP facility; 2. Investigate the protective effects of a thermo-responsive, antioxidant macromolecule for use as a delivery vehicle for autologous iPSC-ECs. Results from this work will also provide critical information regarding the feasibility of using autologous iPSC-ECs from PAD patients for vascular regeneration, which may significantly expand the therapeutic options.
StatusActive
Effective start/end date7/1/196/30/22

Funding

  • American Heart Association (19TPA34890008)

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