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.

Kidney regeneration: Where we are and future perspectives

In 2012,about 16487 people received kidney transplants in the United States,whereas 95022 candidates were on the waiting list by the end of the year.Despite advances in renal transplant immunology,approximately 40%of recipients will die or lose graft within10 years.The limitations of current therapies for renal failure have led researchers to explore the development of modalities that could improve,restore,or replace the renal function.The aim of this paper is to describe a reasonable approach for kidney regeneration and review the current literature regarding cell sources and mechanisms to develop a bioengineering kidney.Due to kidneys peculiar anatomy,extracellular matrix based scaffolds are rational starting point for their regeneration.The perfusion of detergents through the kidney vasculature is an efficient method for delivering decellularizing agents to cells and for removing of cellular material from the tissue.Many efforts have focused on the search of a reliable cell source to provide enrichment for achieving stable renal cell systems.For an efficient bioengineered kidney,these cells must be attached to the organ and then maturated into the bioractors,which simulates the human body environment.A functional bioengineered kidney is still a big challenge for scientists.In the last ten years we have got many improvements on the field of solid organ regeneration;however,we are still far away from the main target.Currently,regenerative centers worldwide have been striving to find feasible strategies to develop bioengineered kidneys.Cell-scaffold technology gives hope to end-stage renal disease patients who struggle with morbidity and mortality due to extended periods on dialysis or immunosupression.The potential of bioengineered organ is to provide a reliable source of organs,which can be refunctionalized and transplanted.