Journal of Biotechnology & Biomaterials
Open Access

Abstract

We have taken human mesenchymal stem cells (hMSCs) that have been genetically engineered to produce Glucagon-like Peptide-1 (GLP-1) fusion peptide and encapsulated them within an alginate microcapsule to provide immunoprotection (cell beads). The cell beads were evaluated in a range of models of cardiovascular disease in order to ascertain if the implanted cells could illicit a beneficial therapeutic effect through the secretion and localized release of paracrine factors from hMSCs. In models of Acute Myocardial Infarction (AMI), cell beads were infused intraarterially, in either a swine embolization model of left ventricular dysfunction or balloon occlusion models of moderate and severe acute myocardial infarction with histological analyses and effects on functional recovery compared with relevant controls. In a model of Vein Graft Disease (VGD), cell beads were applied periadventially around a swine vein-into-artery interposition graft and the effect on neointimal formation and adventitial angiogenesis evaluated. To evaluate potential application in Critical Limb Ischemia (CLI), the therapeutic activity of perivascular transplantation of cell beads was assessed in an immunocompetent mouse model of limb ischemia. In each of the models, implantation of the cell beads was associated with notable functional improvement due to sustained delivery of locoregional paracrine factors secreted from the hMSCs that supports the potential use of the technology in treatment of these disease states. Moreover, in each case there was an additional statistically significant increase in new blood vessels formation. This was identified as a consequence of Vascular Endothelial Growth Factor A (VEGF-A) secretion from the hMSCs.

Biography

Andrew Lewis is the Director of R&D in Innovation at BTG. He specializes in the development of advanced biomedical polymer systems, for instance, to enhance the biocompatibility of implants or to modulate delivery of active agents in the body. He has published ~200 papers (H-index 46), 11 book chapters and 50 patent families/applications in the fields of polymers, biomaterials and drug delivery. He was recently awarded the Chapman Medal for distinguished research in the field of biomedical materials.

Email: andrew.lewis@btgplc.com