Evolving Experimental Platforms to Evaluate Ulcerative Colitis

Abstract

tissue thus altering tissue integrity, anatomy, and physiology subsequently affecting the overall health-related quality of life (HRQoL) of afflicted individuals. [1][2][3] It is estimated that the lifetime financial loss associated with the typical UC patient can be greater than $1 million/patient to cover direct and indirect medical expenses including treatment, hospitalizations, and general medical care. [3][4][5][6][7] As an example, vedolizumab and adalimumab treatment for UC had total direct medical costs of $100 022 and $151 133, respectively, per patient. [8] This number varies greatly depending upon the severity of the disease with a greater expense attributed to those exhibiting a poor clinical disposition. At the domestic level, the total cost to treat UC is estimated to be between $4-14 billion per year which seems to rise on an annual basis. [3,6,7] The specific etiological basis regarding the initiation and progression of UC is currently unknown. Physical manifestations of severe UC take the form of ulcerations affecting the mucosal lining, specifically along the length of the affected large intestine and rectum as depicted in Figure 1. These lesions contain an overabundant accumulation of innate and adaptive immune cells, including T cells, that promote an inflammatory environment Ulcerative colitis (UC) is a multifactorial disease defined by chronic intestinal inflammation with idiopathic origins. It has a predilection to affect the mucosal lining of the large intestines and rectum. Management of UC depends upon numerous factors that include disease pathogenesis and severity that are maintained via medical or surgical means. Chronic inflammation that is left untreated or managed poorly from a clinical stance can result in intestinal ulceration accompanied by resulting physiological dysfunction. End-stage UC is mediated by surgical intervention with the resection of diseased tissue. This can lead to numerous health-related quality of life issues but is considered a curative approach. Regimens to treat UC are ever evolving and find their basis within various platforms to evaluate and treat UC. Numerous modeling systems have been examined to delineate potential mechanisms of action. However, UC is a heterogenous disease spanning unknown genetic origins coupled with environmental factors that can influence disease outcomes and related treatment procedures. Unfortunately, there is no one-size-fits-all model to fully assess all facets of UC. Within the context of this review article, the utility of various approaches that have been employed to gain insight into different aspects of UC will be investigated.

Disease clearance in ulcerative colitis: A new therapeutic target for the future

“…Due to the availability of only less potent drugs, the natural disease course has not been fully elucidated. Over the past few decades, advancements in murine modeling systems have yielded novel mechanisms of disease onset and progression[ 16 ]. This has fueled identification of a wide array of molecular targets, resulting in a rapidly expanding therapeutic armamentarium.…”