Ben Streeter

BME PhD Proposal Presentation 

Date: Thursday, October 3rd, 2019

Time: 10:00 am

Location: HSRB E182

Committee Members: 

Michael E. Davis, PhD (Advisor) 

Younan Xia, PhD

Rebecca Levit, MD

Johnna S. Temenoff, PhD

Josh T. Maxwell, PhD 

Title: Electrospun Nanofiber-Based Patches for the Delivery of c-Kit+ Progenitor Cells

Abstract: 

Congenital heart disease (CHD) affects 8 in 1000 live births and is the number one cause of birth defect-related deaths. Current treatment is surgical correction of the abnormality, but these surgeries are often only palliative and lead to right ventricular heart failure (RVHF). One promising avenue to restore the contractile function of the right ventricle is stem cell therapy. However, stem cell injection is hampered by low cell retention and survival following injection into the heart. Additionally, the reparative capacity of certain stem cell populations, namely c-kit+ progenitor cells (CPCs), declines with age. Therefore, autologous therapies for older CHD patients may be hampered due simply to the patient’s age.

To combat these issues, stem cells can be combined with biomaterials that serve as a delivery vehicle to enhance cell survival and modulate reparative paracrine release in vivo. The aim of this study is to combine nanofibrous polycaprolactone (PCL) scaffolds and cardiac CPCs to create a biomaterial/cardiac cell patch capable of treating RVHF in CHD patients. Further, we investigate the effects of PCL nanofiber alignment and inclusion of extracellular matrix (ECM)-mimicking adhesion factors gelatin and fibronectin on CPCs of different ages. We hypothesize that PCL/CPC patches will improve cardiac function in RVHF patients, and that fiber alignment and inclusion of gelatin and fibronectin in PCL scaffolds will affect patch performance by changing CPC function and paracrine release. We further hypothesize that these changes will be CPC age-dependent.

To test this hypothesis, we will perform the following specific aims: Aim 1) Determine the CPC age-dependent effects and underlying mechanisms of PCL patch fiber alignment and the inclusion of gelatin and fibronectin on CPC behavior and reparative capacity. Aim 2) Determine if a PCL/CPC patch implanted onto a failing RV improves cardiac function. Accomplishing these aims will demonstrate the validity of an electrospun nanofibrous PCL patch as an effective biomaterial for CPC implantation and will determine the effects of the patch microenvironment on the reparative function of differently aged CPCs.