Researchers at Indiana University School of Medicine, in collaboration with the University of Alabama at Birmingham and five other institutions, are exploring new regenerative medicine methods to better treat vascular health complications from type 2 diabetes. These are used to identify and develop new therapeutic therapies to further differentiate or mature human induced pluripotent stem cells (hiPSCs) into a specific mesoderm subset of cells that demonstrate vascular reparative properties.
According to Chang-Hyun Gil, a PhD, a postdoctoral fellow in the Department of Surgery and the first author of the study. In this study, we focused on the retinal vessel in type 2 diabetes. Our findings demonstrate the safe, effective, and robust hiPSC-derived mesoderm subset for use as a novel therapy to rescue ischemic tissues and repair blood vessels.
Investigators reprogrammed diabetic and non-diabetic peripheral blood cells into hiPSCs after injecting intoanimalmodels with type 2 diabetic murine (T2D) retinal problems. Results indicated a significant improvement in visual acuity and electroretinograms with a restoration of vascular perfusion. These findings suggest that hiPSC-derived vascular reparative cells may serve as a source of endothelial properties in diabetic patients.
Genetically engineered hiPSCs do not face ethical challenges ESCs possess that limit their possible use, and hiPSCs are becoming more widely accepted in study design and implementation as a cell therapy for human diseases.
According to the Centers for Disease Control and Prevention in the United States, more than 37 million people have diabetes, including both young adults aged 18 to 44 years of age and adults aged 45 to 64. These complications are attributable to substantial metabolic disturbances that damage the cardiovascular, visual, peripheral nerve, and renal systems. In 2019, more than 11 percent of adults ages 18 and older reported severe vision difficulties or blindness, and about 1.87 million adults were diagnosed with severe cardiovascular disease.
Dr. Gil''s research represents a monumental step forward in the use of induced pluripotent stem cells in treating diabetes complications, according to Michael P. Murphy, MD, a Cryptic Medical Research Foundation professor in vaccinology at the University of Michigan, a vascular surgeon atIU Healthand an expert witness.
High-tech hiPSC has been transformed into a specific mesoderm subset, which was enriched to extract endothelial cells with vessel reparative properties similar to the ECF. Endothelial cells are found in the inner lining of blood vessels, lymph vessels, and the heart, which is a major factor in regulating blood flow and inflammatory reactions.
Gil said the specific mesoderm subset expressing KDR, NCAM1, and APLNR (KNA+mesoderm) has increased capacity to differentiate into ECFC and form functional blood vessels in vivo, indicating that mesoderm populations have improved the function of neural retina and optokinetic nystagmus studies.
The next translational step of the project is to transfer the hiPSC into S-KNA+cells in large-scale manufacturing processes, according to Mikhail Yoder, MD, a distinguished professor emeritus and research advisor for theIndiana University Innovation and Commercialization Office. Selected aspects of this research have been licensed by Vascugen, Inc., which is based on the development of vascular reparative cells from pluripotent stem cells.
Maria B. Grant, MD, the former Marilyn Glick Professor of Ophthalmology at the University of Iowa, and the current chair of UAB''s ophthalmology. Grant said this is a repeat of a grant she and Yoder have completed over the years regarding stems cells and how they can be used to repair blood vessels in the eye. While hiPSCs may take a long time to grow, the study team simplified the process to reduce the time it takes to grow them and make them more feasible to
We took the stem cells and hiPSC cells and examined them, according to UAB. Science is really team science. I bring all the eye experience and some stem cell experience, and Dr. Yoder brings a lot of stem cell experience. It''s a complementary collaboration.
I want to express my greatest gratitude to Dr. Yoder, Dr. Grant, and Dr. Murphy for their assistance. He will remember Yoder for his dedication, passion, patience, and kindness, and Murphy for supporting him in his final study.