Purified Exosome Product for Rotator Cuff Repair and Regeneration

The overall goal of this project is to develop a novel biological therapy to treat rotator cuff tears, which is a common injury that causes shoulder pain and dysfunction. We will use a biological product extracted from human expired banked blood developed at Mayo Clinic and combine it with a fibrin glue that used in clinic to increase the rotator cuff healing capacity. We will test this drug effectiveness of treating rotator cuff tears using a rat model.

Chunfeng Zhao, MD

Development Of Novel Proteolytic Targeting Chimeras That Promote Cartilage Regeneration

Osteoarthritis (OA) is the most common form of arthritis and a leading cause of doctor visits, chronic disability, and joint pain. OA occurs when articular cartilage, a shock absorbing tissue between bones, degenerates because of injury, inflammation, or aging. No medications are available to regenerate cartilage or prevent its degradation. The goal of this project is to develop and test a new class of molecules that hold the potential to increase cartilage regeneration without affecting other tissues.

Jennifer Westendorf, PhD

Unraveling Cardiac Maturation to improve Congenital Heart Disease Therapies

The goal of this project is to study the process of cardiac maturation, which involves changes that happen in the heart from birth to adulthood. There are many differences between a newborn heart and an adult heart, including the size of the contractile cells as well as the abundance of other cell types that are present in the heart. There are currently no medical therapies that are specific to pediatric patients with heart disease and that is in part because we don't know how the pediatric heart is different from the adult heart.

Jop van Berlo, MD, PhD

Rapidly Endothelialized Vascular Bypass Grafts From Autologous Adipose Microvessels

The project aims to develop and test a novel method to create replacement blood vessels that are rapidly seeded with cells derived from a simple liposuction from the patient. These cells include cells (pericytes) considered to be stem cells as well as the normal blood contacting (endothelial) cells. They should prevent blood clotting in the graft and thus reduce, if not eliminate, the need to treat the patient with blood thinners. The method should even be fast enough for urgent coronary artery bypass patients who need a bypass graft with a few days.

Robert Tranquillo, PhD

A multi-omics approach for the identification of species-specific developmental states and speed during interspecies chimerism

1. Construct integrative models that characterize the developmental states and rhythms of early embryogenesis. 2. Identify the developmental differences in host and donor cells in chimeric embryos of evolutionary close and distant species. 3. Identify key regulators of the developmental timing of host and donor cells in chimeric embryos. 4. Our long-term goal is to establish the basis for a better generation of human organs in host animals through interspecies chimerism.

Juan Carlos Rivera-Mulia, PhD

Augmenting Liver Regeneration at the Single Cell Level

This application examines the mechanisms by which targeting the molecule YAP with medications can facilitate liver regeneration. We propose that YAP is functioning in multiple cell types within the liver and that the mechanisms differ between the cell types. The results of these studies have the potential to identify new optimization strategies for using these medications, and to identify new therapeutic targets to further augment liver regeneration.

Rory Smoot, MD

Advancing a genetically edited biosensor platform in human induced pluripotent stem cell-derived cardiac muscle for personalized medicine and drug discovery

This proposal focuses on leveraging advances in cardiac stem cell biology to forge new therapeutic modalities for combating heart disease, the leading cause of combined morbidity and mortality among Minnesotans.

Joseph Metzger, PhD

Mechanistic studies on a congenital hydrocephalus causing mutation in Trim71

Congenital hydrocephalus is a major cause of childhood morbidity. Mutations in Trim71, a conserved stem-cell-specific RNA-binding protein, cause this disease, however, the molecular basis for pathogenesis mediated by these mutations remains unknown. Here, we plan to address this knowledge gap by determining the molecular mechanisms by which a disease-causing mutation in Trim71 leads to congenital hydrocephalus.

Qiuying Liu, PhD

Pre-clinical evaluation of drug treatments to prevent vision loss from Dry Age-Related Macular Degeneration using patient-derived iPSC-RPE

Dry Age related macular degeneration is a chronic disease of aging that causes progressive loss of vision due to damage to the RPE cell layer in the retina. There are no current treatments for dry AMD. Studies have indicated that personalized approaches are likely required to match patients with Dry AMD with drug therapies to treat their disease. Our group generates RPE from induced pluripotent stem cells derived from tissue biopsies from AMD patients to test drugs in the laboratory that may prevent loss of RPE and preserve vision.

James Dutton, PhD

MSC facilitated cartilage recycling for hip defects

The overall goal of this study is to test the safety and feasibility for a one-stage cartilage restoration procedure for symptomatic defects of the hip.  This will be achieved using the patient’s own recycled cartilage cells combined with culture expanded allogeneic AMSCs (RECLAIM).  We will assess 1) the local and systemic safety of this RECLAIM procedure, 2) improvement in pain and function in the target hip; and 3) the effect on bone and cartilage structures using MRI.

Aaron Krych, MD