Human Stem Cell Use: Embryonic Stem Cell
Directed Differentiation of Specialized Endothelial Cells
Vascular endothelial cells (EC) or endothelial progenitor cells (EPC) derived from stem cells could potentially lead to a variety of clinically relevant therapeutic applications, including various strategies for treating heart and vascular diseases. However, because EC exhibit a variety of functionally distinct subphenotypes, it is important to be able to generate the appropriate endothelial type. […]
Biophysical Determinants of Early Embryonic Stem Cell Fate Specification
Regenerative therapies require effective differentiation of stem cells to cell types that are functionally identical to those found in vivo. Many current differentiation protocols merely involve optimization of proteins added to the culture media, but do not consider the microenvironmental context in which cells differentiate during development or tissue repair. When we include the biophysical […]
Metabolically-driven epigenetic changes in iPSC reprogramming
Generation of induced pluripotent stem cells (iPSCs) from somatic cells through cellular reprogramming offers tremendous potential for therapeutics, the study of disease states, and elucidation of developmental processes. Central to the process of generating a pluripotent cell from a somatic cell is an energy-dependent epigenetic reconfiguration event that must occur to produce iPSCs with characteristics […]
Paracrine and synaptic mechanisms underlying neural stem cell-mediated stroke recovery
Stem cell therapy holds promise for the almost million Americans yearly who suffer a stroke. Preclinical data have shown that human neural stem cells (hNSCs) aid recovery after stroke, resulting in a major effort to advance stem cell therapy to the clinic, and we are currently transitioning our hNSC product to the clinic for stroke […]
Metabolic regulation of cardiac differentiation and maturation
Cells in the body take up nutrients from their environment and metabolize them in a complex set of biochemical reactions to generate energy and replicate. Control of these processes is particularly important for heart cells, which need large amounts of energy to drive blood flow throughout the body. Not surprisingly, the nutritional requirements of heart […]
Assessing the mechanism by which the Bone Morphogenetic Proteins direct stem cell fate
Our goal is to use the mechanisms that generate neuronal networks to create neurons from stem cells, to either replace diseased and damaged tissue or as a source of material to study disease mechanisms. A key focus of such regenerative studies is to restore function to the spinal cord, which is particularly vulnerable to damage. […]
A novel druggable mechanism to safeguard stem cell genome
Safeguarding the genome is essential for cells’ proper functions, and more importantly for safe and efficacious applications involving pluripotent stem cells and adult stem cells. However, how pluripotent or somatic stem cells maintain genome integrity during self-renewal, differentiation, and reprogramming is still largely unknown. We recently identified a small molecule drug that exhibits unprecedented abilities […]
Generation of a functional thymus to induce immune tolerance to stem cell derivatives
Stem cell research offers the promise of replacing missing or damaged tissues in the treatment of disease. Stem-cell-derived transplants still face problems with rejection as in traditional organ transplants. Several drugs can prevent rejection but also suppress the immune system, leaving patients vulnerable to infections and cancer. To avoid rejection without using drugs requires re-educating […]
Defining links between chromatin state and developmental competence
This proposal aims to define fundamental mechanisms that underlie the production of human pancreas and liver cells. The proposed research seeks to advance the development of stem cell-based therapies for diabetes and chronic liver disease. Diabetes is characterized by insulin deficiency due to destruction and/or malfunction of insulin-producing beta cells in the pancreas. Diabetic patients […]
Promoting survival and countering hypertrophy of pluripotent stem cell (PSC)-derived chondrocytes
Degenerative joint disease, also known as osteoarthritis, currently affects more than 20 million people in the USA alone, making articular cartilage restoration one of the major priorities in medicine. Articular chondrocyte progenitors are likely to be present only early in development, which explains why previous attempts to engineer articular cartilage using adult stem cells have […]