Engineering an endocrine Neo-Pancreas by repopulation of a decellularized rat pancreas with islets of Langerhans

Decellularization of pancreata and repopulation of these non-immunogenic matrices with islets and endothelial cells could provide transplantable, endocrine Neo- Pancreata. In this study, rat pancreata were perfusion decellularized and repopulated with intact islets, comparing three perfusion routes (Artery, Portal Vein, Pancreatic Duct). Decellularization effectively removed all cellular components but conserved the pancreas specific extracellular matrix. Digital subtraction angiography of the matrices showed a conserved integrity of the decellularized vascular system but a contrast emersion into the parenchyma via the decellularized pancreatic duct. Islets infused via the pancreatic duct leaked from the ductular system into the peri- ductular decellularized space despite their magnitude. TUNEL staining and Glucose stimulated insulin secretion revealed that islets were viable and functional after the process. We present the first available protocol for perfusion decellularization of rat pancreata via three different perfusion routes. Furthermore, we provide first proof-of-concept for the repopulation of the decellularized rat pancreata with functional islets of Langerhans. The presented technique can serve as a bioengineering platform to generate implantable and functional endocrine Neo-Pancreata

Bioreactor technologies to support liver function in vitro

Liver is a central nexus integrating metabolic and immunologic homeostasis in the human body, and the direct or indirect target of most molecular therapeutics. A wide spectrum of therapeutic and technological needs drives efforts to capture liver physiology and pathophysiology in vitro, ranging from prediction of metabolism and toxicity of small molecule drugs, to understanding off-target effects of proteins, nucleic acid therapies, and targeted therapeutics, to serving as disease models for drug development. Here we provide perspective on the evolving landscape of bioreactor-based models to meet old and new challenges in drug discovery and development, emphasizing design challenges in maintaining long-term liver-specific function and how emerging technologies in biomaterials and microdevices are providing new experimental models.National Institutes of Health (U.S.) (R01 EB010246)National Institutes of Health (U.S.) (P50-GM068762-08)National Institutes of Health (U.S.) (R01-ES015241)National Institutes of Health (U.S.) (P30-ES002109)5UH2TR000496-02National Science Foundation (U.S.). Emergent Behaviors of Integrated Cellular Systems (CBET-0939511)United States. Defense Advanced Research Projects Agency. Microphysiological Systems Program (W911NF-12-2-0039

Cell transplantation for regeneration and function recovery before and after oncological resections.

Background. Cell transplantation provides the unique possibility to preoperatively optimize organ function or to re-establish organ function after oncological resection. Transplantation of autologous islets of Langerhans after pancreatic resection and transplantation of hematopoietic stem cells (HSC) or mesenchymal stromal cells (MSC) to optimize liver regeneration before and after liver resection are important examples of this therapy. Results. The transplantation of autologous islets of Langerhans is an internationally well-established procedure and implicates clear benefits for the metabolic control and quality of life of patients otherwise suffering from pancreoprivic diabetes mellitus. The positive effects of stem cell transplantation on the regeneration capacity of the liver is now preclinically well described and is currently under evaluation in clinical studies. Besides paracrine effects, the shedding of microparticles, which influence cell-cell communication by horizontal transfer of microRNA appears to be responsible for the immunomodulatory and pro-regenerative effects; however, it is still not completely understood how these cells interact with regenerating liver tissue. Tissue engineering techniques may have a profound impact on future oncological surgery but are so far limited to individual therapy attempts and preclinical experiments. Conclusion. The possibility of an autologous islet transplantation should be evaluated before pancreatic resection for certain indications (e.g. chronic pancreatitis, pancreatic trauma and complications after resection). Recent single center data demonstrate that this procedure can be safely and efficiently performed even for neoplastic pancreatic diseases. Due to encouraging preclinical results, the impact of stem cell transplantation for patients suffering from liver disease or for cancer patients before or during extended liver resection is currently under evaluation in clinical studies