Stem cell therapies in the treatment of diabetic retinopathy and keratopathy

Abstract

Nonproliferative diabetic retinopathy (DR) is characterized by multiple degenerative changes that could be potentially corrected by stem cell therapies. Most studies so far have attempted to alleviate typical abnormalities of early retinopathy, including vascular hyperpermeability, capillary closure and pericyte dropout. Success was reported with adult stem cells (vascular progenitors or adipose stem cells), as well as induced pluripotent stem cells from cord blood. The cells were able to associate with damaged vessels in both pericyte and endothelial lining positions in models of DR and ischemia-reperfusion. In some diabetic models, functional amelioration of vasculature and electroretinograms was noted. Another approach for endogenous progenitor cell therapy is to normalize dysfunctional diabetic bone marrow and residing endothelial progenitors using NO donors, PPAR-d and -g agonists, or inhibition of TGF-b. A potentially important strategy would be to reduce neuropathy by stem cell inoculations, either naïve (e.g., paracrine-acting adipose stem cells) or secreting specific neuroprotectants, such as ciliary neurotrophic factor or brain-derived neurotrophic factor that showed benefit in amyotrophic lateral sclerosis and Parkinson's disease. Recent advances in stem cell therapies for diabetic retinal microangiopathy may form the basis of first clinical trials in the near future. Additionally, stem cell therapies may prove beneficial for diabetic corneal disease (diabetic keratopathy) with pronounced epithelial stem cell dysfunction.

Advances in bone marrow stem cell therapy for retinal dysfunction

“…Still others have shown that transient in vitro inhibition of TGF-beta improves the function of circulating endothelial progenitor cells from diabetic subjects and enhances the engraftment of these cells in eyes with diabetic retinopathy (Bhatwadeker et al, 2010). Such a treatment may potentially enhance the therapeutic potential of the CD34 + cells from both bone marrow and peripheral blood and normalize dysfunctions induced by the diabetic environment (Kramerov and Ljubimov, 2016). …”

Diabetic complications in the cornea

“…Specific gene therapy of limbal compartment harboring LESC was able to restore the marker expression levels and accelerate healing of large epithelial wounds (Saghizadeh et al, 2014). In severe cases of diabetes and with pronounced neuropathy, LESC may become seriously dysfunctional (Ueno et al, 2012; Zhou et al, 2015), and a transplantation of healthy cells may become an option (Kramerov and Ljubimov, 2016). Normal LESC may be obtained from donors, especially in cases of bilateral stem cell deficiency.…”

Mesenchymal Stem Cells Improve Healing of Diabetic Foot Ulcer

“…Nowadays, a growing number of diseases can be improved via wide applications of stem cell transplantation, such as congenital cataract [12], diabetic retinopathy and keratopathy [13], myocardial infarction [14], ocular surface burns [15, 16], serious skin burns [17, 18], Parkinson's disease [19], Huntington's disease [20], and especially DFU [21]. Accumulating evidence has pointed out that mesenchymal stem cells (MSCs) may enhance wound healing [22–24] and be served as a cell source for many tissue engineering applications including bone regeneration [25], cartilage regeneration [26–28], myocardial regeneration [29], neurogenesis [30, 31], inflammatory bowel diseases [32], and DFU [33, 34].…”