Treatments for fibrosis development and progression: Lessons learned from preclinical models and potential impact on human conditions such as scleroderma, pulmonary fibrosis, hypertrophic scarring and tendinopathies

Abstract

Progressive fibrosis of a tissue or organ in response to a damaging insult may result in loss of organ function if the acute response is excessive, or a chronic fibrotic response is initiated due to the persistence of the insult. In the author’s laboratory over the past several years, a number of preclinical models of fibrosis or fibrogenic responses have been characterized for the effectiveness of various treatment approaches to either prevent or impede fibrosis development and progression to identify commonalities and translatable research directions that could provide insights into human diseases. These have mainly included either chemically induced pulmonary fibrosis models or overt physical injury models in rats, pigs and rabbits. Some preliminary studies in human populations have also been undertaken. The interventions evaluated have included fibrinolytic agents and drugs targeting specific cell populations. The results indicate that some approaches lend themselves to modifying fibrotic reactions in some models and not others, while others may have a more generalized impact on fibrogenic responses due to interference with abnormal cell functions in the injury environment.