ECE2015 Guided Posters Diabetes and obesity – basic (7 abstracts)
Topical application of CD362+ human mesenchymal stem cells (cyndacel-M) seeded in Excellagen scaffold augments wound healing and increases angiogenesis in a diabetic rabbit ulcer model
Swapnil Patil 1 , Xizhe Chen 1 , Luke Watson 2 , Paul Loftus 2 , Lisa O’ Flynn 2 , Lois Chandler 3 , Gabor Rubanyi 3 , Stephen Elliman 2 & Timothy O’Brien 1,
1Regenerative Medicine Institute (REMEDI) and Biosciences Research Building, National University of Ireland (NUIG), Galway, Ireland; 2Orbsen Therapeutics, National University of Ireland, Orbsen Building, Galway, Ireland; 3Cardium Therapeutics, San Diego, California, USA; 4Department of Medicine, Galway University Hospital (GUH), Galway, Ireland.
Non-healing foot ulcers are a major complication in diabetic patients. Mesenchymal stem cells (MSCs) are known to promote angiogenesis with improved wound healing. Orbsen Therapeutics has identified a novel antibody (CD362+) which can be used to prospectively FACS-isolate CD362+CD45− MSC from human bone marrow with enhanced MSC/MNC purity ratios of up to 1/4. Excellagen matrix was used to seed the cells as biomaterials are well reported to enhance viability and therapeutic efficacy of cells. In this study, 1 million of CD362+, CD362− and plastic adherent human MSCs were seeded in an Excellagen matrix and applied to cutaneous wounds in an alloxan-induced diabetic rabbit ear ulcer for a 1 week period. Statistical analysis between groups revealed that the wounds treated with an Excellagen-CD362+ cell treatment demonstrated increased percentage wound closure with more prominent neovasculature. The wound sections were immunohistochemically stained by using CD31 and GSL-B4 lectins to study neovasculature. In stereological analysis, significantly increased surface density, length density and reduced radial diffusion distance was observed in the Excellagen-CD362+ cell treated wound groups in comparison to untreated wounds. A subsequent study compared the beneficial effects of a combination treatment (IV delivery of cells at 2×106 cells/kg plus topical treatment) to topical treatment alone. A slight increase was observed in percentage wound healing in combination versus topical treated animals but this difference was not significant. There was no lowering of blood glucose levels in the combination treated animal groups over the seven day study period. Hence, with improved wound healing potential and augmenting angiogenesis, topical treatment with these specifically selected CD362+ MSCs seeded in an Excellagen matrix may lead to a new therapeutic product to treat non-healing diabetic foot ulcers.
Disclosure: This research was supported by funding from EU FP7-HEALTH-2012-INNOVATION-1 grant number 305736 (REDDSTAR, Repair of Diabetic Damage by Stromal Cell Administration).
Volume 37
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Endocrine Abstracts
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