Regenerative Treatment of Diabetic Retinal Microvascular Pathology Using Stem Cells

Article: Study shows human induced pluripotent stem cells improve visual acuity, vascular health
Source: Indiana University School of Medicine
Published: March 10, 2022

Vascular density assessment in retinas of diabetic mice injected with
either saline or KNA cells. All parameters indicate a restoration
of retinal vascularity with KNA cell treatment compared to saline
control injection. Notably, blood vessel growth was robust
without giving rise to teratomas.

According to the Center for Disease Control and Prevention, more than 37 million people in the U.S. have diabetes, with complications affecting the microvasculature of organs such as the kidneys and eyes and of peripheral nerves. A team of researchers conducted a multi-site study investigating the use of human induced pluripotent stem cells (hiPSCs) as a regenerative approach in the treatment of microvascular diseases, such as in diabetic retinopathy. In this pre-clinical study, investigators genetically reprogrammed diabetic and non-diabetic peripheral blood cells into hiPSCs and matured the cells into a specific mesoderm subset, KNA+ mesoderm, that had high clonal proliferative potential and specification into cells similar to endothelial colony forming cells (ECFC). These stem cells were delivered by intravitreal injection to mice with type 2 diabetic retinal dysfunction. Results showed that the ECFCs formed functional blood vessels in vivo, effectively increasing vascular density and perfusion to retinal tissue. Electroretinography and optokinetic nystagmus vision testing showed significant improvement in neural retinal response and visual acuity, respectively. They hypothesized that the hiPSC-derived vascular reparative cells may serve as a source of endothelial precursors. The authors report, "Transcriptomic analysis showed that differentiation of hiPSCs derived from diabetics into KNA+ cells was sufficient to change baseline differences in gene expression caused by the diabetic status and reprogram diabetic cells to a pattern similar to KNA+ cells derived from nondiabetic hiPSCs." That is, these findings show a pre-clinical proof-of-concept that KNA+ cells can be used to restore perfusion and correct vascular dysfunction.

My rating of this study: ⭐⭐⭐

Gil C, Chakraborty D, Vieira CP, et al. "Specific mesoderm subset derived from human pluripotent stem cells ameliorates microvascular pathology in type 2 diabetic mice." Science Advances.  8(9). 4 March 2022. https://www.science.org/doi/10.1126/sciadv.abm5559