Porcine pancreas extracellular matrix as a platform for endocrine pancreas bioengineering Sayed-Hadi Mirmalek-Sani 1,¶ , Giuseppe Orlando 1,2,3,¶ , John McQuilling 1,2 , Rajesh Pareta 1 , David Mack 1,# , Marcus Salvatori 1,* , Alan C Farney 2,3 , Robert J Stratta 2,3 , Anthony Atala 1,2 , Emmanuel C Opara 1,2 , and Shay Soker 1,2,@ 1 Wake Forest Institute for Regenerative Medicine, Winston Salem, NC, USA 2 Wake Forest School of Medicine, Winston Salem, NC, USA 3 Department of General Surgery, Section of Transplantation, Wake Forest School of Medicine, Wake Forest Baptist Health, Winston Salem, NC, USA Abstract Emergent technologies of regenerative medicine have the potential to overcome the limitations of organ transplantation by supplying tissues and organs bioengineered in the laboratory. Pancreas bioengineering requires a scaffold that approximates the biochemical, spatial and vascular relationships of the native extracellular matrix (ECM). We describe the generation of a whole organ, three-dimensional pancreas scaffold using acellular porcine pancreas. Imaging studies confirm that our protocol effectively removes cellular material while preserving ECM proteins and the native vascular tree. The scaffold was seeded with human stem cells and porcine pancreatic islets, demonstrating that the decellularized pancreas can support cellular adhesion and maintenance of cell functions. These findings advance the field of regenerative medicine towards the development of a fully functional, bioengineered pancreas capable of establishing and sustaining euglycemia and may be used for transplantation to cure diabetes mellitus. 1. Introduction The treatment of diabetes mellitus remains inadequate. Although exogenous insulin therapy is effective at preventing acute metabolic decompensation in type 1 diabetes, less than 40% of patients achieve and maintain therapeutic targets [1]. As a result, hyperglycemia-related organ damage remains a significant cause of morbidity and mortality among the diabetic population. Intensive glycemic control achieved through dietary modification, physical activity, oral hypoglycemics and exogenous insulin can significantly reduce, but not eliminate, the microvascular and macrovascular complications of diabetes mellitus. Current best-practice guidelines for the management of diabetes are centered upon life-long lifestyle and pharmaceutical intervention. While these measures reduce the incidence of © 2013 Elsevier Ltd. All rights reserved. @ Corresponding author: Shay Soker PhD, Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston Salem, NC, 27157, USA, ssoker@wakehealth.edu. ¶ equal contribution * current address: School of Medicine, University of Newcastle-upon-Tyne, UK # current address: Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author Manuscript Biomaterials. Author manuscript; available in PMC 2014 July 01. Published in final edited form as: Biomaterials. 2013 July ; 34(22): 5488–5495. doi:10.1016/j.biomaterials.2013.03.054. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript