Dissecting Allo-Sensitization After Local Administration of Human Allogeneic Adipose Mesenchymal Stem Cells in Perianal Fistulas of Crohn's Disease Patients

Adipose mesenchymal stem cells (ASC) are considered minimally immunogenic. This is due to the low expression of human leukocyte antigens I (HLA-I), lack of HLA-II expression and low expression of co-stimulatory molecules such as CD40 and CD80. The low rate of observed immunological rejection as well as the immunomodulatory qualities position ASC as a promising cell-based therapy for the treatment of a variety of inflammatory indications. Yet, few studies have addressed relevant aspects of immunogenicity such as ASC donor-to-patient HLA histocompatibility or assessment of immune response triggered by ASC administration, particularly in the cases of presensitization. The present study aims to assess allo-immune responses in a cohort of Crohn's disease patients administered with allogeneic ASC for the treatment of complex perianal fistulas. We identified DSA generation in a proportion of patients and observed that patients showing preexisting immunity were prone to generating DSA after allogeneic therapy. Noteworthy, naïve patients generating DSA at week 12 showed a significant reduction in DSA titer at week 52 whereas DSA titer was reduced in pre-sensitized patients only with no specificities against the donor administered. Remarkably, we did not observe any correlation of DSA generation with ASC therapeutic efficacy. In vitro complement dependent cytotoxicity studies have revealed limited cytotoxic levels based upon HLA-I expression and binding capacity even in pro-inflam...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

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Contributors : Carolina Serena ; Miriam Ejarque ; Alfonso Saera ; Joan Vendrell ; Sonia Fern ández-VeledoSeries Type : Methylation profiling by arrayOrganism : Homo sapiensPathological expansion of adipose tissue (AT) is supported by adipocyte precursors, termed adipose-derived stem cells (ASCs). Elucidation of mechanisms underlying ASC function may lead to therapeutic interventions to use in cell therapy treatments on Crohn ’s disease patients. Using epigenome-wide association studies, we explored the impact of Crohn’s disease on the methylation signature of human ASCs
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Methylation profiling by array Homo sapiens Source Type: research
Medical treatment remains the mainstay of perianal disease management for CD; however, aggressive surgical management should be considered for severe or recurrent disease. In all cases of perianal CD, medical and surgical treatments should be used in tandem by a multidisciplinary team. Significant development has been made in the treatment of Crohn's-related fistulas, particularly minimally invasive options with recent clinical trials showing success with mesenchymal stem cell applications. Inevitably, some patients with severe refractory disease may require fecal diversion or proctectomy. When considering reversal of a di...
Source: Surgical Clinics of North America - Category: Surgery Authors: Source Type: research
Conclusion: Radiation therapy and pelvic operation for cancer were more common causes than birth injury, and these causes of rectovaginal fistula were the most important prognostic factors. An individualized approach and repeated surgeries with complex or newly developed procedures, even among high-risk causes of fistula, may be necessary to achieve successful closure. PMID: 31508396 [PubMed]
Source: Annals of Surgical Treatment and Research - Category: Surgery Tags: Ann Surg Treat Res Source Type: research
Conditions:   Crohn's Disease;   Fistula;   Anal Fistula;   Pouch, Ileal;   Pouches, Ileoanal Intervention:   Drug: mesenchymal stem cells (MSCs) Sponsor:   The Cleveland Clinic Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Publication date: Available online 23 August 2019Source: Stem Cell ResearchAuthor(s): Lanzi Gaetana, Masneri Stefania, Ferraro Rosalba Monica, Genova Elena, Piovani Giovanna, Barisani Chiara, Pelin Marco, Stocco Gabriele, Decorti Giuliana, Bramuzzo Matteo, Giliani SilviaAbstractCrohn's disease is a debilitating and incurable chronic inflammatory bowel disease, affecting millions of individuals worldwide, with an increasing frequency. Surgery must be applicable in half of the cases often with a disabling course, and pharmacological treatments may have adverse complications. We generated three isogenic clones of iPSCs from p...
Source: Stem Cell Research - Category: Stem Cells Source Type: research
AbstractAplastic anemia (AA) has been reported to be associated with inflammatory bowel disease (IBD), but mostly with ulcerative colitis (UC). Little is known about the associations between AA and Crohn ’s disease (CD). We aim to determine the portraits of patients with AA-CD. Among a total of 657 patients with CD registered in Xijing Hospital of Digestive Diseases IBD center from January 2008 to October 2018, the patients diagnosed with concurrent AA were reviewed. Clinical presentation, medical history, endoscopic features, response to treatment, and prognosis in this set of patients were collected. Six male patie...
Source: Annals of Hematology - Category: Hematology Source Type: research
Abstract The introduction of biologics such as anti-tumor necrosis factor (TNF) monoclonal antibodies followed by anti-integrins has dramatically changed the therapeutic paradigm of inflammatory bowel diseases (IBD). Furthermore, a newly developed anti-p40 subunit of interleukin (IL)-12 and IL-23 (ustekinumab) has been recently approved in the United States for patients with moderate to severe Crohn's disease who have failed treatment with anti-TNFs. However, these immunosuppressive therapeutics which focus on anti-inflammatory mechanisms or immune cells still fail to achieve long-term remission in a significant p...
Source: World Journal of Gastroenterology - Category: Gastroenterology Authors: Tags: World J Gastroenterol Source Type: research
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