Our goal is to develop a new treatment strategy that improves outcomes in individuals with chronic spinal cord injury. Studies will contribute to the identification of a drug target that increases neural connections in the brain and spinal cord capable of restoring function, long after the initial injury. We will also determine if this new approach can augment existing therapies to further enhance neural regeneration in the chronically injured adult brain and spinal cord.

The clinical prognosis for patients with hypertrophic cardiomyopathy (HCM) is very poor and the only long-term alternative is heart transplant. Our goal is to develop a living, human, model of HCM in a dish so that we can develop new therapeutics that target disease onset and early-stage progression. We will do this by modifying our recently developed, 3D printed, chambered model of a living cardiac muscle pump.

The goal of this research is to facilitate the generation of human organs and cells for transplantation and repair of the human body. The generation of animal organs and cells from stem cells has been achieved in laboratory animals by applying methods of stem cell complementation in gene edited blastocysts to produce intraspecies chimeras. Attempts to generate human organs and cells by this approach has thus far failed to be achieved because of interspecies barriers.

Retinal vascular diseases, e.g., diabetic retinopathy, are a leading cause of blindness and place a significant burden on individual patients as well as the State of Minnesota. Diseased retinal blood vessels in retinopathies indirectly impair the proper function of nerve cells in the retina, contributing to vision loss. Here, we will use a retinopathy mouse model and a highly innovative drug candidate to restore the function of blood vessels. We will test if the restoration of the retinal blood vessels also leads to improved function of retinal nerve cells.

Cardiovascular diseases are common and deadly. It is estimated that the U.S. has limited blood supply for those that require transfusions (there are 5.6M blood donations each year in the U.S., but an estimated 14.6M more are required) that are needed for acute injuries or chronic diseases. The aim of this grant proposal is to perform proof-of-concept experiments aimed at the development of blood in vitro and to engineer an interspecies chimeric pig as a platform for the generation of human blood.

Obesity remains a significant health problem that affects above 30% of Minnesotans. Obesity increases susceptibility to injury by interfering with mesenchymal stem/stromal cells (MSCs), which reside in many organs and tissues, and promote local repair, making exogenous delivery of MSCs an attractive therapeutic tool. However, the mechanisms by which obesity injures human MSCs, and the impact of these alterations on their reparative capacity, remain unknown.

Neuromuscular diseases (NMDs) are life-altering conditions typically resulting in disability, poor quality of life, and eventual long-term dependency on care-givers. Many NMDs do not have cures or substantive treatments. We will develop and utilize cell and animal models to study regenerative defects in one type of NMD, GNE myopathy. We anticipate that the tools and knowledge gained here will help facilitate the development of new therapeutic options for GNE myopathy patients.

In the US, ~726,000 patients have end-stage renal disease (ESRD) requiring chronic hemodialysis, which will double in the coming decade. Optimal hemodialysis and clearance of uremic toxins requires a vascular access through an arteriovenous fistula (AVF). Unfortunately, AVFs fail due to venous neointimal hyperplasia (VNH) that leads to venous stenosis formation. AVF patency at one year is estimated to be approximately 62%. Currently, no effective and durable therapies prevent venous stenosis formation.

1. Deployment of scalable and affordable regenerative solutions for patients who have experienced heart attack. 2. Establishment of safety for a novel exosome platform as an off-the-shelf regenerative therapeutic in the setting     of myocardial infarction. 3. Gain insight into efficacy signals for this first in class and first in man application of exosomes in cardiovascular     disease. 4. Establish Minnesota as a leader in exosome-based regenerative technologies.