SCI Faculty members awarded Regenerative Medicine Minnesota grants for 2022-2024

The Minnesota State Legislature funds the Regenerative Medicine Minnesota initiative to support research and biobusiness development to improve or increase access to regenerative medicine throughout the state.  For the period 2022 to 2024, eight Stem Cell Institute Faculty members have received these research grants.  The projects funded are:

DISCOVERY SCIENCE (research that provides basic knowledge)

Elizabeth Bradley, PhD
Epigenetic Reprogramming to Enhance Bone Regeneration in Type 2 Diabetes

Type 2 diabetes is a common chronic condition that affects Minnesotans' quality of life.  Reducing the body's own ability to heal is among its health impacts. Our work suggests that epigenetic reprogramming of innate immune cells enhances bone healing in pre-clinical, non-diabetic models. This project will evaluate the effects of epigenetic reprogramming to bone healing in a high fat diet (HFD)-induced model of type 2 diabetes. We will also determine if epigenetic programming limits enhanced commitment to bone resorbing osteoclasts observed in type 2 diabetes and if a novel regulator of cellular metabolism, Lipocalin 2, controls innate immune cell responses and glucose utilization.

Troy Lund, MD, PhD
Peroxisome Transfer Enables Bone Marrow Regeneration

The goal of this project is to describe a new field of science: peroxisome transfer. We believe the bone marrow uses a mechanism of peroxisome transfer to support regeneration after injury.  The project aims to demonstrate this process in vitro and in vivo using our exclusively created ubiquitous peroxisome reporter mouse.
 
Joseph Metzger, PhD
Advancing a genetically edited biosensor platform in human induced pluripotent stem cell-derived cardiac muscle for personalized medicine and drug discovery

This project 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.
 
Juan Carlos Rivera-Mulia, PhD
A multi-omics approach for the identification of species-specific developmental states and speed during interspecies chimerism

Generation of human organs in animal hosts such as pigs, is a promising alternative for transplantation therapy. However, developmental differences between species constitute a major roadblock. In this study, we aim to construct integrative models of gene regulation during early embryogenesis of distinct species that can improve stage-matching of donor cells and host embryos, and enable better generation of human transplantable organs for regenerative medicine.
 
Jop van Berlo, MD, 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. Our studies will lay the groundwork on which we can begin to develop regenerative strategies and medical therapies for pediatric patients with heart disease.

TRANSLATIONAL RESEARCH (research addressing specific medical problems)

Atushi Asakura, PhD
Skeletal muscle angiogenesis and dystrophin

This project aims to:  1) elucidate how muscle vascular regeneration is regulated during muscle remodeling.  2) identify the interactions between muscle stem cells and endothelial cells. and 3) elucidate how much dystrophin is regulating muscle angiogenesis and vascular function.

 
James Dutton, 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 (Dry AMD) 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 obtained from AMD patients. We then use the iPSC-RPE to test drugs in the laboratory that may prevent loss of RPE and preserve vision. This translational grant builds on previous drug testing results to test the therapeutic potential of optimal drugs identified for individual patients to preserve their RPE by testing cell survival in drug treated cells under stress and identifying drug dose responses using the patient's iPSC-RPE lines.


Ferenc Toth, DVM, PhD and Timothy O'Brien, DVM, PhD
Preclinical Evaluation of Multi-tissue Organoid-Derived Chondrocytes for the Treatment of Focal Cartilage Defects

The proposed study will evaluate the utility of human iPSC-derived chondrocytes, manufactured in a highly efficient manner without the use of xenobiotic agents, in repairing induced cartilage defects. Conducting these studies in a translationally relevant large animal model will create a solid foundation for subsequent clinical introduction of this one-stage, off-the-shelf, economically feasible, allogeneic chondrocyte implantation method allowing treatment of a broad selection of human patients afflicted with focal cartilage injuries.

 
Robert Tranquillo, 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.

 

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