Intravitreal injections of human bone marrow CD34+ stem cells prevent further retinal damage associated with diabetic retinopathy.
Researchers at the University of California, Davis, have shown that stem cell injections elicit a protective effect on retinas damaged by diabetes. Using a diabetic retinopathy mouse model system, the scientists demonstrated that intravitreal injections of human bone marrow CD34+ stem cells resulted in homing and integration of the cells into the damaged retina and preservation of the retinal vasculature. The study provides a potential early intervention treatment to prevent further retinal damage and vision loss.
People with diabetes can develop an eye disease called diabetic retinopathy. The condition occurs when high blood sugar levels cause damage to blood vessels in the retina. These blood vessels can swell and leak, or they can close, stopping blood from passing through, all of which can lead to neuro-degeneration or loss of vision. Currently, there is no available treatment, but investigations into various stem cells as a regenerative treatment for this condition is ongoing. For example, transplantation studies using bone marrow mesenchymal stem cells (MSCs) or CD133+ hematopoietic stem cells (HSCs) have shown positive results in slowing the progression of the disease.
In this study, the investigators chose a specific type of stem cell, bone marrow CD34+ stem cells, as a potential cell type in the treatment of diabetic retinopathy for multiple reasons. First, CD34+ stem cells are a mix population of HSCs and endothelial progenitor cells, which allows them to play a role in both tissue repair and angiogenesis. Second, intravitreal injection of these cells home to areas of damaged retinal vasculature. Last, intravitreal injection of the cells into patients suffering from retinal ischemia showed vision improvement.
For their preliminary research, the investigators were interested in tracking the cells to determine if they could localize to damaged areas, and integrate into and regenerate the damaged tissue. To start, CD34+ stem cells were isolated from human bone marrow and labeled with an enhanced green fluorescent protein (EGFP) to track the cells in vivo. The cells were injected into the right eye of a diabetic retinopathy mouse model while a placebo control was injected into the left eye. Using a mouse model system can help determine if there are beneficial effects of the cells before advancing to clinical studies in humans. Advanced retinal imaging of the living eye and immunohistochemistry post-mortem confirmed homing and integration of the cells to the retinal surface and vasculature after one- and four-weeks post-injection. Microarray analysis post-mortem also revealed changes in the expression of 162 murine retinal genes. The major molecular pathways affected by the stem cell injection included pathways implicated in the pathogenesis of diabetic retinopathy, such as the Toll-like receptors and MAP kinase pathways. Additionally, measurements of the retinal vascular density, taken four weeks after intravitreal injections, increased in eyes treated with CD34+ stem cells suggesting that the retinal vessels were being preserved and possibly regenerated. Although an increase in vascular density was seen, further long-term studies will need to be explored to determine the regenerative effects of the cells.
The findings show that intravitreal injection of human bone marrow CD34+ stem cells results in retinal homing and integration and shows a protective effect of the retinal vasculature in a diabetic retinopathy model. Furthermore, the preliminary data suggest the feasibility of this application as a treatment for early-stage disease progression and offers support for future long-term studies into the mechanism of action of bone marrow CD34+ stem cells.
The authors isolated human bone marrow CD34+ stem cells from whole bone marrow procured by StemExpress.
Yazdanyar A. et al. (2019) Effects of Intravitreal Injection of Human CD34+ Bone Marrow Stem Cells in a Murine Model of Diabetic Retinopathy. Exp Eye Res Doi:10.1016/j.exer.2019.107865.