Research Interests: Adult Mesenchymal and Endothelial Progenitor Stem Cells, Diabetes, and Obesity
My laboratory studies adult stem cell survival and differentiation, particularly in presence of high glucose. Adult mesenchymal stem cells (MSCs) are the building blocks of our body. These cells act to repair and regenerate old and dying cells in tissues in bone, muscle, and cartilage and adipose tissue. During the course of repair and regeneration, MSCs mature in ways that can maintain health or lead to clinical problems such as obesity and osteoporosis and even cardiovascular disease, all of which are more likely to occur in people with diabetes. MSCs exposed to particular cell milieus influence the cell's ability to differentiate into fat, bone, cartilage, or muscle. Our goal is to modify these cell environments (such as hyperglycemia and hyperlipidemia) so MSCs differentiate into bone, muscle, or other beneficial tissue rather than fat. As part of this research, we are learning how to harness the potent growth factors produced by endothelial progenitor stem cells (EPCs), another adult stem cell type, to help coax MSCs to grow, survive, and differentiate to maintain health and prevent diseases by secreting specific growth factors. We study human mesenchymal stem cells from bone marrow, adipose tissue, pancreatic islets, and other tissues and modify the environment to address complications of diabetes and obesity.
The other principal focus of our lab is translational. As a clinical endocrinologist, I am interested in how substances secreted from inflamed adipose tissue and endothelial cells in hyperglycemic prediabetic and diabetic patients influence cardiovascular health. This is particularly relevant because patients with diabetes and prediabetes are at high risk for heart disease and stroke. Given that both vascular endothelium and adipose tissue cells are endocrine organs, our mission is to identify the cross talk between these two systems and ultimately improve endothelial function. We are also interested in identifying novel vascular biomarkers, such as EPCs (CD34/KDR+ve cells), and utilizing them for regeneration and repair.
Center for Endocrine and Metabolic Research
Center of Excellence in Apoptosis Research
Sen S, Yoon YS, Rasko JE, Aikawa R, et al. Autologous transplantation of endothelial progenitor cells genetically modified by AAV viral vector delivering IGF-1 gene following myocardial infarction. Hum Gene Ther. 2010;21(10):1327-1334.
Dobrucki L, Tsutsumi Y, Sen S, Aikawa R, et al. Analysis of angiogenesis induced by local IGF-1 gene delivery after myocardial infarction: Application and Validation of integrin targeted imaging by SPECT-CT: J Mol Cell Cardiol. 2010;48(6):1071-1079.
Sen S, Conroy S, Hynes S, Katusic Z, O'Brien T, et al. Gene delivery to the vasculature mediated by low-titre adeno-associated virus serotypes 1 and 5. J Gene Med. 2008;10(2):143-151.
Sen S, Strappe P, O'Brien T. Gene transfer in endothelial dysfunction and hypertension. Methods Mol Med. 2005;108:299-314.
Sumner A, Sen S, Kushner H, et al. Determining the waist circumference in African Americans which best predicts insulin resistance. Obesity. 2008;16(4):841-845.
Sen S, Davani B, Gershengorn MC, et al. Medium conditioned by human endothelial progenitor cells (hEPCs) increases survival and insulin expression during differentiation of human islet-derived precursor cells (hIPCs). Diabetes. 2009;58(1):A622.
Young Investigator Award, American Heart Association 2005
Winner of Outstanding Abstract Award at 2010 ENDO Society Annual Session