Kidney Regeneration by Human Regenerative Therapy

Animal models are essential for understanding the pathogenetic mechanisms governing the onset and progression of various kidney diseases and for pre-clinically testing novel, more effective, treatments for the patients afflicted with renal impairment. Despite the presence of several non-rodent models, rats and mice remain principal and indispensable species used by investigators in the field of nephrology. Emphasis is placed on several well-established models, such as the ischemic or reperfusion acute renal failure model, remnant kidney model, and unilateral ureteral obstruction model. Undoubtedly, establishment of authentic animal models is of vital importance in delineating the mechanisms of a range of human kidney diseases and in evaluating the feasibility and efficacy of novel therapeutic interventions.

Kidney diseases are fatal and can cause death and its mortality rate is almost 6-8% annually.

Kidney tissue derived from human pluripotent stem cells was generated using organ development mechanism of xenogeneic foetuses, suggesting possibility of generating humanised kidney using animal metanephroi as a scaffold. To apply his concept to humans, the size of the generated animal needs to be increased using larger host animal. Pigs are considered the most suitable f the possible larger animals models, because of their physiological and anatomical similarities to humans. The strategy that underlies humanised kidney generation assumes the transplantation of xenogenic foetal anlagen to adult patients. For this pig metanephroi has to be studied to see the similarities with human nephron so that the differences can be identified so that when the kidney is transplanted into the person the probability of rejection of the graft is already calculated and taken care off. The use of cloned pigs would be beneficial for this type of transplantation study because metanephroi from a cloned pig foetus could be transplanted into a syngeneic adult cloned pig. Thus, engraftment and growth of the graft could be evaluated without being affected by immune rejection. Kidney regeneration using pig metanephroi as a scaffold has potential not only in human medicine but also for companion animals.

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