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Exploring ASC Treatment for Diabetes-related Vascular Damage

Review of “The pericytic phenotype of adipose tissue-derived stromal cells is promoted by NOTCH2” from STEM CELLS by Stuart P. Atkinson

The elevated levels of blood sugar associated with diabetes (hyperglycemia) can lead to a breakdown in contact-dependent signaling between pericytes and microvascular endothelial cells (ECs) [1] leading to the loss of pericytes and subsequent vascular damage. Treatment with mesenchymal-like stem cells derived from adipose tissues (ASCs) represents a potentially effective means to solve vasculature-related problems, as ASCs have the ability to functionally replace lost pericytes [2, 3]. 

Now, a new STEM CELLS study from the laboratory of Vincenzo Terlizzi (University of Groningen, The Netherlands) explores the potential for ASC treatment in various in vitro and in vivo models of diabetes-related vascular disease and identifies the NOTCH2 protein as a novel regulator of the pericytic phenotype of ASCs [4]. 

Initial in vitro analyses highlighted high levels of NOTCH2 expression in ASCs and established the requirement of NOTCH2 expression for pericyte-like vasculogenic characteristics. Processes mediated by NOTCH2 promoted included migration towards an EC-secreted pericyte chemoattractant, vessel formation by ECs in 2D and 3D co-cultures, and adhesion to ECs. Of significant importance, the study did not observe alterations to the expression of NOTCH2 or related proteins following exposure of ASCs to the high glucose levels characteristic of diabetes.

Moving in vivo, the authors injected ASCs with reduced NOTCH2 expression (via the stable expression of a short hairpin RNA) into the eyes of a mouse model suffering from oxygen-induced retinal blood vessel abnormalities. Interestingly, while the modified ASCs did not engraft into the retinal microvasculature and lost their migratory abilities, the paracrine angiogenic capacity of the ASCs did not differ from non-modified control ASCs and both sets of mice presented reconstituted retinal capillary beds.

The authors see great promise in NOTCH2-expressing ASCs as a possible treatment for diabetes-related vascular damage although they underline the necessity of further “explorations”, including those delineating the response of ASCs to the signals generated by the pathological extracellular microenvironment into the diabetic retina.

For news on all the new explorations into ASCs and their potential to treat vascular damage, stay tuned to the Stem Cells Portal!


  1. Pfister F, Feng Y, vom Hagen F, et al., Pericyte migration: a novel mechanism of pericyte loss in experimental diabetic retinopathy. Diabetes 2008;57:2495-502.
  2. Park SS, Cell Therapy Applications for Retinal Vascular Diseases: Diabetic Retinopathy and Retinal Vein Occlusion. Investigative Ophthalmology & Visual Science 2016;57:ORSFj1-ORSFj10.
  3. Hajmousa G, Elorza AA, Nies VJ, et al., Hyperglycemia Induces Bioenergetic Changes in Adipose-Derived Stromal Cells While Their Pericytic Function Is Retained. Stem Cells Dev 2016;25:1444-53.
  4. Terlizzi V, Kolibabka M, Burgess JK, et al., The Pericytic Phenotype of Adipose Tissue-Derived Stromal Cells Is Promoted by NOTCH2. STEM CELLS 2018;36:240-251.