In a multisite, early-stage study recently published in the journal Science Advances, investigators genetically reprogrammed diabetic and non-diabetic peripheral blood cells to hiPSCs and matured the cells. these cells into specialized vascular comparator cells. When injected into animal models of type 2 diabetic retinal dysfunction (T2D), the results showed significant improvement in visual acuity and electrocardiogram with restoration of vascular perfusion. They hypothesized that hiPSC-derived vascular comparator cells could serve as a source of endothelial precursors that would display vascular comparability properties in vivo in subjects with diabetes. this way.
“Unlike the use of embryonic stem cells (ESCs), transgenic hiPSCs do not present the ethical challenges that ESCs have that limit their possible use, and hiPSCs are increasingly recognized as a Possible alternatives in research design and application as a cell therapy for humans Gil says.
In 2019, more than 11% of adults 18 years of age and older reported severe vision problems or blindness, and more than 1.87 million adults were diagnosed with serious cardiovascular disease.
“This work by Dr. Gil represents a giant step forward in the application of cells,” said Michael P. Murphy, MD, Research Professor of Vascular Biology in the Institute for Vascular Biology Research at IU School. Induced pluripotent root in the treatment of complications of diabetes. Medicine, a vascular surgeon at IU Health and Eskenazi Health and a co-author of the study.
The researchers transformed hiPSCs into a specific dermal subset enriched to induce endothelial cells with angiogenic properties similar to those of endothelial colony-forming cells (ECFCs). . Endothelial cells are cells found in the inner lining of blood vessels, lymphatic vessels, and the heart and are key players in the regulation of vascular function and inflammatory responses. Endothelial cells control blood flow and regulate the transfer of proteins from the blood into tissues.
Gil said the specific dermal subset expressing KDR, NCAM1 and APLNR (KNA + mesoderm) exhibits an enhanced ability to differentiate into ECFCs and form functional blood vessels in vivo and to regulate dermal populations. vascular remodeling of injured retinal vessels. The electrocardiogram showed enhanced neuroretinal function and photodynamic nystagmus studies showed improved visual acuity.
“The next interpretive step of the work is to translate the reported research protocols for the differentiation of hiPSCs into S cells,” said Mervin C. Yoder, MD, Indiana professor emeritus and research advisor. -KNA+ into large-scale production processes. Center for Regenerative Medicine and Engineering. Yoder is another co-author of the study and the scientific founder of Vascugen, a company driven to advance treatments for life-threatening conditions caused by microvascular conditions. “Selected aspects of this work have been licensed by Vascugen, Inc., through the Indiana University Office of Commerce and Innovation, which is focusing on the development of vascular regenerative cells. from induced pluripotent stem cells.”
Another study co-author is Maria B. Grant, MD, former Marilyn Glick Professor of Ophthalmology at the Eugene IU School of Medicine and the Marilyn Glick Eye Institute and now chair of ophthalmology at UAB. This is a highly translational study, said Grant, which is a continuation of the funding she and Yoder have done over the past 20 years related to stem cells and how they can be used to repair blood vessels in the eye. While hiPSCs can take a long time to develop, the team has simplified the process to shorten their development time and make them more viable to translate into a therapeutic for humans to treat. Repair blood vessels in the eye.
“At UAB, we take stem cells and hiPSC cells and study them,” she said. “Science is really team science. I bring all my eye experience and some stem cell experience, and Dr. Yoder brings a lot of stem cell experience. It’s a partnership. complement each other.”
“I would like to extend my deepest thanks to Dr Yoder, Dr Grant and Dr Murphy for their support,” Gil said. He will remember Yoder for “his dedication, passion, patience, and kindness” and Murphy for assisting him in completing his research.
Source: Eurekalert
