Application of dual energy CT in the diagnosis of amiodarone lung toxicity as a cause of lung mass.

BACKGROUND: Diagnosis of amiodarone lung toxicity on computerized tomography (CT) can be challenging especially in the presence of mass-like consolidation. Additional causes of mass-like consolidation including malignancy and pneumonia should be excluded, sometimes requiring tissue sampling. CASE: Here we present a case of amiodarone lung toxicity, with diagnosis suspected based on patient's history of chronic cardiac disease, amiodarone treatment, and imaging characteristics. Evaluation with dual energy CT demonstrated high iodine content in the mass-like consolidation further supporting the diagnosis. Biopsy of the mass-like consolidation confirmed amiodarone toxicity. CONCLUSION: Dual energy CT has potential utility in differentiating mass-like consolidation from other etiologies such as malignancy or pneumonia.

Regeneration and bioengineering of transplantable abdominal organs: current status and future challenges.

INTRODUCTION: The most critical issue to organ transplantation is the identification of new sources of organs. The present manuscript illustrates the state-of-the-art regenerative medicine (RM) investigations aiming to manufacturing abdominal organs for transplant purposes. AREAS COVERED: This manuscript focuses on research in the bioengineering and regeneration of kidneys, insulin-producing cells, livers and small bowel. The main technology currently under development exploits the seeding of cells on supporting scaffolding material. Despite favorable preliminary results obtained with relatively simple, hollow organs, when more complex organs are considered, the scenario changes dramatically. Investigations are still in early stages, and clinical translation is not yet foreseeable based on current knowledge and information. Obstacles are numerous but we believe the critical factor hampering success is lack of in-depth understanding of the extracellular matrix (ECM) and cell-ECM interactions, as well as the mechanisms with which organs develop in utero. EXPERT OPINION: The success of RM to generate transplantable abdominal organs relies heavily on progress in (stem) cell therapies, developmental and ECM biology, and in the thorough understanding of the intricate relationship and interplay between cells and the ECM. This will require enormous investments in financial and medical resources, which ideally should be embarked upon by governments, the private sector and academia.

Liver bioengineering: current status and future perspectives.

The present review aims to illustrate the strategies that are being implemented to regenerate or bioengineer livers for clinical purposes. There are two general pathways to liver bioengineering and regeneration. The first consists of creating a supporting scaffold, either synthetically or by decellularization of human or animal organs, and seeding cells on the scaffold, where they will mature either in bioreactors or in vivo. This strategy seems to offer the quickest route to clinical translation, as demonstrated by the development of liver organoids from rodent livers which were repopulated with organ specific cells of animal and/or human origin. Liver bioengineering has potential for transplantation and for toxicity testing during preclinical drug development. The second possibility is to induce liver regeneration of dead or resected tissue by manipulating cell pathways. In fact, it is well known that the liver has peculiar regenerative potential which allows hepatocyte hyperplasia after amputation of liver volume. Infusion of autologous bone marrow cells, which aids in liver regeneration, into patients was shown to be safe and to improve their clinical condition, but the specific cells responsible for liver regeneration have not yet been determined and the underlying mechanisms remain largely unknown. A complete understanding of the cell pathways and dynamics and of the functioning of liver stem cell niche is necessary for the clinical translation of regenerative medicine strategies. As well, it will be crucial to elucidate the mechanisms through which cells interact with the extracellular matrix, and how this latter supports and drives cell fate.

Immunoisolation: where regenerative medicine meets solid organ transplantation.

Immunoisolation refers to an immunological strategy in which nonself antigens present on an allograft or xenograft are not allowed to come in contact with the host immune system, and it is implemented to prevent allorecognition and avoid immunosuppression. In this setting, the two most promising technologies, encapsulation of pancreatic islets (EPI) and immunocloaking (IC), are used. In the case of EPI, islets are inserted in capsules that, allow exchange of oxygen, nutrients and other molecules. In the case of IC, a natural nanofilm is injected prior to renal transplantation within the vasculature of the graft with the intent to pave the inner surface of the vascular lumen and camouflage the antigens located on the membrane of endothelia cells. Significant progress achieved in experimental models is leading EPI and IC to clinical translation.

Regeneration and bioengineering of the gastrointestinal tract: current status and future perspectives.

The present review aims to illustrate the strategies that are being implemented in regenerative medicine to treat diseases that affect the digestive tract. Possible avenues are twofold: organ bioengineering, where cells are seeded on biological or synthetic scaffolding materials ex vivo and allowed to either mature in bioreactors or be implanted without undergoing any maturation; and regeneration per se, where the diseased tissue or organ is regenerated by recapitulation of its multi-step ontogenesis. This latter avenue may be induced either in vivo or ex vivo. While bioengineering technology has already manufactured segments of the digestive tract and sphincters, pure regeneration of any segment of the digestive tract has not yet been described. However, models of regeneration extrapolated from simple organisms are elucidating the complex yet fascinating mechanisms that regulate the ontogenesis of the digestive tract and are paving the way for the development of new regenerative technologies and methods.