A fistula is defined as an abnormal communication between two epithelium-lined surfaces, and fistula-in-ano consists of an abnormal tract connecting the anal canal or rectum with the perianal skin or vagina [1]. When developing in Crohn disease, fistulas—considered an independent phenotype and referred to as perianal disease [2]— represent a grievous and disabling condition, resulting in significant human and health care costs because of a high relapse rate despite the use of biologics combined with surgery as standard therapy [3]. The advent of novel therapeutic strategies based on minimally inva- sive surgery and mesenchymal stem/stromal cells (MSCs) offers an unprecedented opportunity. Following the results of a phase 3 trial in which 212 patients were randomly assigned to receive a single local injection of 120 millions of allogeneic adipose tissue-derived MSCs (darvadstrocel, formerly Cx601) or placebo, which showed that MSCs performed better to achieve combined remission (51.5% versus 35.6% at week 24) within a shorter time [4], the European Medicines Agency granted marketing authorization (Alofisel; Takeda, Tokyo, Japan) for use in refractory cases [5]. Since that time, several issues have been raised that hamper its use and jeopardize the knowledge regarding its therapeutic value. This prompted the authors to high- light in this editorial the misconceptions and hurdles that, based on the authors’ own experience, hinder an appropriate application of this new treatment and to establish a list of recommendations whose implementation may help this therapy find its right positioning in the management of this dismal condition.
Misconceptions, hurdles and recommendations regarding the use of mesenchymal stem/stromal cells in perianal Crohn disease
Rachele Ciccocioppo;
2023-01-01
Abstract
A fistula is defined as an abnormal communication between two epithelium-lined surfaces, and fistula-in-ano consists of an abnormal tract connecting the anal canal or rectum with the perianal skin or vagina [1]. When developing in Crohn disease, fistulas—considered an independent phenotype and referred to as perianal disease [2]— represent a grievous and disabling condition, resulting in significant human and health care costs because of a high relapse rate despite the use of biologics combined with surgery as standard therapy [3]. The advent of novel therapeutic strategies based on minimally inva- sive surgery and mesenchymal stem/stromal cells (MSCs) offers an unprecedented opportunity. Following the results of a phase 3 trial in which 212 patients were randomly assigned to receive a single local injection of 120 millions of allogeneic adipose tissue-derived MSCs (darvadstrocel, formerly Cx601) or placebo, which showed that MSCs performed better to achieve combined remission (51.5% versus 35.6% at week 24) within a shorter time [4], the European Medicines Agency granted marketing authorization (Alofisel; Takeda, Tokyo, Japan) for use in refractory cases [5]. Since that time, several issues have been raised that hamper its use and jeopardize the knowledge regarding its therapeutic value. This prompted the authors to high- light in this editorial the misconceptions and hurdles that, based on the authors’ own experience, hinder an appropriate application of this new treatment and to establish a list of recommendations whose implementation may help this therapy find its right positioning in the management of this dismal condition.
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