M101 - Localized Administration of Mesenchymal Stem Cell-derived Exosomes for Treatment of Refractory Perianal Fistula in Crohn’s Disease Patients: Phase-II Clinical Trial

Monday, June 3, 2024

11:29 AM – 11:35 AM ET, USA

Location: Room 314-317

Abstract Podium Presenter(s)

Alireza Hadizadeh, M.D

M.D postdoctorate research fellow
Northshore University HealthSystem (The University of Chicago Pritzker School of Medicine)
Northshore University HealthSystem (The University of Chicago Pritzker School of Medicine)
chicago, IL, United States

All relevant financial disclosures have been managed and will be listed below.
This individual has no financial relationships with ineligible companies.

Author(s)

rA

reza Akbari Asbagh, n/a

Medical Student
Tehran university of medical sciences
Tehran, Tehran, Iran

Disclosure information not submitted.
fA

foroogh Alborzi Avanaki, TUMS

Associate professor
TUMS
Tehran, Arkansas, United States

Disclosure information not submitted.
AH

Asieh Heirani-Tabasi, Ph.D. (Applied Cell Scinces)

Researcher
Tehran heart center
Tehran, Tehran, Iran

Disclosure information not submitted.
bb

behnam behboudi, n/a

Surgeon
Colorectal research center,Imam Khomeini hospital complex,Tehran University of medical sciences,Tehran, d
Tehran, Tehran, Iran

Disclosure information not submitted.
mf

mohammad sadegh fazeli, MD

Surgeon
Professor of colorectal surgery
Tehran, Tehran, Iran

Disclosure information not submitted.
NE

Nasser Ebrahimi Daryani, n/a

Professor
Tehran University of Medical Sciences
Tehran, Tehran, Iran

Disclosure information not submitted.
mk

mohammad-reza keramati, MD

Surgeon
Colorectal research center,Imam Khomeini hospital complex,Tehran University of medical sciences,Tehran, Iran
Tehran, Tehran, Iran

Disclosure information not submitted.
ak

alireza kazemeini, n/a

Professor
Tehran University of Medical Science
Tehran, Tehran, Iran

Disclosure information not submitted.
ak

amir keshvari, M.D. professor of surgery

professor of surgery, colorectal surgery division
tehran university of medical sciences
tehran, Tehran, Iran

Disclosure information not submitted.
hp

haleh pak, n/a

Surgeon
Tehran university of sciences
Tehran, Tehran, Iran

Disclosure information not submitted.
hn

hengameh nazari, md radiologist

radiology specialist
esfahan university of medical sciences
illinois, Illinois, United States

Disclosure information not submitted.

Senior Author(s)

SA

Seyed Mohsen Ahmadi Tafti, MD

Surgeon
Colorectal research center,Imam Khomeini hospital complex,Tehran University of medical sciences,Tehran, Iran
Tehran, Tehran, Iran

Disclosure information not submitted.

Purpose/Background: Crohn’s disease is a chronic autoimmune gastrointestinal condition which can potentially be complicated by perianal fistulas. Anti-TNF therapy, as the standard and established treatment, is sometimes ineffective. Mesenchymal stem cell (MSC)-derived exosomes are lipid bilayer structures that have demonstrated potent immunomodulatory effects and are promising in treating refractory perianal fistulas. The aim of this study was to assess the safety and efficacy of treatment with MSC-derived exosomes in Crohn’s disease patients with refractory perianal fistulas.

Methods/Interventions: This is an ongoing prospective, single-arm, phase 2 clinical trial approved by the US clinical trial registry (NCT05499156). Included in the study were patients diagnosed with Crohn’s disease with an active perianal fistula who had failed at least one course of anti-TNF therapy and had not received any therapy within the past six months.
After obtaining the umbilical cord from elective caesarean sections, umbilical cord MSCs were seeded into flasks and passaged. The conditioned media from third passage MSCs were collected and centrifuged for 10 min at 400 g to remove suspended cells, 30 min at 2,500 g to remove debris and apoptotic bodies, and subsequently ultracentrifuged for 120 min at 100,000 g. dynamic light scattering, flowcytometry and western blotting were used to characterise the presence of exosomes. All media and solutions in this study were cGMP grade, and we followed the guideline set by Minimal Information for Studies of Extracellular Vesicles 2018 (MISEV2018).
For the injection procedure, an Eisenhammer Retractor was utilised to expose the internal orifice. The tract was irrigated with saline several times using a small catheter to remove pus and faecal matter. A flexible fistula probe was inserted into the tract after irrigation. The tissue surrounding the tract was injected with 5 mL of an exosome solution (0.5 × 1010 particles/mL, 50 μg/mL), using the probe as a guide. The injection depth of the soft tissue and sphincters of the anus was ∼2–3 mm. Patients were observed for 48 hours, after which they were discharged. All patients received three treatment courses of MSC-derived exosomes at 2-month intervals and were followed for six months after the last injection. Closure of the fistula tract on clinical exam and MRI was the primary outcome. Secondary outcomes included comparison of fistula discharge volume pre- and post-treatment and assessment of any adverse events throughout the study.

Results/Outcomes: A total of 20 patients were recruited for this phase of the study, out of which 13 patients completed the follow-up period of 6 months and were included in the final analysis. A total of 27 fistula tracts were observed in those patients. Eight (61.5 %) patients had full fistula closure; One (7.6 %) patient was completely unresponsive to treatment. Four (30.7%) patients with multiple fistulas had resolution of some of their tracts. Out of 27 tracts, six remained active (22.2%). All patients reported decreased discharge volume. No adverse outcomes or complications were observed.

Conclusion/Discussion: These preliminary results show that the administration of MSC-derived exosomes is safe and effective in the treatment of refractory Crohn’s disease-related fistula.