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Wilkinson T, Booth K. Operative Management of Perianal Crohn's Disease. Surg Clin North Am 2025; 105:277-288. [PMID: 40015816 DOI: 10.1016/j.suc.2024.09.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/01/2025]
Abstract
The management of perianal Crohn's disease is challenging and complex and requires a multidisciplinary approach as a favorable working relationship between gastroenterologists and colorectal surgeons is necessary to provide excellent care for this patient population. The use of biologic therapy has impacted the treatment of this disease process, but surgical options have failed to reach the success rates seen in cryptoglandular and traumatic pathologies of the anus. The general management of perianal disease involves control of sepsis, control of anorectal symptoms, minimizing resultant complications and avoidance of proctectomy when possible.
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Affiliation(s)
- Taylor Wilkinson
- Department of Colorectal Surgery, University of Tennessee Chattanooga, Chattanooga, USA
| | - Kristina Booth
- Department of Surgery, Univeristy of Oklahoma Health Sciences, 800 SL Young Boulevard Suite 9000, Oklahoma City, OK 73104, USA.
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Mazzaro MC, de Paula AEC, Pascoal LB, Genaro LM, Pereira IM, Rodrigues BL, Oliveira PDSP, Leal RF. Optimizing Treatment Outcomes in Crohn's Disease: A Comprehensive Systematic Review and Meta-Analysis of Regenerative Therapies with Emphasis on Platelet-Rich Plasma. Pharmaceuticals (Basel) 2024; 17:1519. [PMID: 39598430 PMCID: PMC11597121 DOI: 10.3390/ph17111519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Revised: 10/19/2024] [Accepted: 10/26/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND/OBJECTIVES Crohn's disease (CD) is a chronic inflammatory disorder that significantly affects patients' quality of life; conventional treatments often provide limited relief. METHODS This systematic review and meta-analysis explored the potential of regenerative therapies, particularly platelet-rich plasma (PRP), as an adjunctive treatment for CD. The study protocol was registered with PROSPERO (CRD42024576683), and a comprehensive search was conducted across major databases, such as PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. The search included terms related to CD and PRP. Studies assessing the efficacy of PRP in CD treatment were selected. Statistical analysis was conducted using the PICO framework with R software (version 4.3.2) and meta-package. RESULTS Of the 29 studies identified, 10 met the inclusion criteria, comprising pilot studies and controlled trials. Nine studies focused on Crohn's disease perianal fistulas (CDPF), and one focused on colonic CD. Among 138 patients with CDPF, 82.44% showed some fistula healing after PRP treatment, with 48.05% achieving complete resolution. In a sub-analysis, combining PRP with a stromal vascular fraction (SVF) resulted in a 58.62% complete healing rate, whereas combining PRP with adipose-derived stem cells (ASCs) showed even higher efficacy at 85.89%. PRP treatment alone resulted in a lower complete healing rate of 38.51%. PRP was well tolerated, with minor side effects such as localized pain. CONCLUSIONS These findings suggest that PRP, especially when combined with stem cells, offers a promising new approach for treating CD. However, larger trials are needed to confirm its long-term benefits and refine its clinical applications.
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Affiliation(s)
- Marcia Carolina Mazzaro
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, School of Medical Sciences, University of Campinas (Unicamp), Campinas 13083-878, Brazil
- Healthy Sciences Institute, Federal University of Jataí (UFJ), Jataí 75804-615, Brazil
| | | | - Livia Bitencourt Pascoal
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, School of Medical Sciences, University of Campinas (Unicamp), Campinas 13083-878, Brazil
| | - Livia Moreira Genaro
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, School of Medical Sciences, University of Campinas (Unicamp), Campinas 13083-878, Brazil
| | - Isabela Machado Pereira
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, School of Medical Sciences, University of Campinas (Unicamp), Campinas 13083-878, Brazil
| | - Bruno Lima Rodrigues
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, School of Medical Sciences, University of Campinas (Unicamp), Campinas 13083-878, Brazil
| | - Priscilla de Sene Portel Oliveira
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, School of Medical Sciences, University of Campinas (Unicamp), Campinas 13083-878, Brazil
| | - Raquel Franco Leal
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, School of Medical Sciences, University of Campinas (Unicamp), Campinas 13083-878, Brazil
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Adamina M, Minozzi S, Warusavitarne J, Buskens CJ, Chaparro M, Verstockt B, Kopylov U, Yanai H, Vavricka SR, Sigall-Boneh R, Sica GS, Reenaers C, Peros G, Papamichael K, Noor N, Moran GW, Maaser C, Luglio G, Kotze PG, Kobayashi T, Karmiris K, Kapizioni C, Iqbal N, Iacucci M, Holubar S, Hanzel J, Sabino JG, Gisbert JP, Fiorino G, Fidalgo C, Ellu P, El-Hussuna A, de Groof J, Czuber-Dochan W, Casanova MJ, Burisch J, Brown SR, Bislenghi G, Bettenworth D, Battat R, Atreya R, Allocca M, Agrawal M, Raine T, Gordon H, Myrelid P. ECCO Guidelines on Therapeutics in Crohn's Disease: Surgical Treatment. J Crohns Colitis 2024; 18:1556-1582. [PMID: 38878002 DOI: 10.1093/ecco-jcc/jjae089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Indexed: 07/28/2024]
Abstract
This article is the second in a series of two publications on the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the management of Crohn's disease. The first article covers medical management; the present article addresses surgical management, including preoperative aspects and drug management before surgery. It also provides technical advice for a variety of common clinical situations. Both articles together represent the evidence-based recommendations of the ECCO for Crohn's disease and an update of prior ECCO Guidelines.
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Affiliation(s)
- Michel Adamina
- Department of Surgery, Cantonal Hospital of Fribourg & Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland
| | - Silvia Minozzi
- Department of Epidemiology, Lazio Regional Health Service, Rome, Italy
| | | | | | - Maria Chaparro
- Gastroenterology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa [IIS-Princesa], Universidad Autónoma de Madrid [UAM], Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBEREHD], Madrid, Spain
| | - Bram Verstockt
- Department Gastroenterology & Hepatology, University Hospitals Leuven, KU Leuven, Belgium
- Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - Uri Kopylov
- Department of Gastroenterology, Sheba Medical Center, Ramat Gan, Israel
| | - Henit Yanai
- IBD Center, Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Stephan R Vavricka
- Department of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland
| | - Rotem Sigall-Boneh
- Pediatric Gastroenterology and Nutrition Unit, The E. Wolfson Medical Center, Holon, Israel
- Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology and Metabolism, University of Amsterdam, Amsterdam, The Netherlands
| | - Giuseppe S Sica
- Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology and Metabolism, University of Amsterdam, Amsterdam, The Netherlands
- Department of Surgery, Università Tor Vergata, Roma, Italy
| | | | - Georgios Peros
- Department of Surgery, Cantonal Hospital Winterthur, Winterthur, Switzerland
| | - Konstantinos Papamichael
- Center for Inflammatory Bowel Diseases, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Nurulamin Noor
- Department of Medicine, University of Cambridge, Cambridge, UK
| | - Gordon William Moran
- National Institute of Health Research Nottingham Biomedical Research Centre, University of Nottingham and Nottingham University Hospitals, Nottingham, UK
- Translational Medical Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, UK
| | - Christian Maaser
- Outpatients Department of Gastroenterology, University Teaching Hospital Lueneburg, Lueneburg, Germany
| | - Gaetano Luglio
- Department of Public Health, University of Naples Federico II, Naples, Italy
| | - Paulo Gustavo Kotze
- Health Sciences Postgraduate Program, Pontificia Universidade Católica do Paraná [PUCPR], Curitiba, Brazil
| | - Taku Kobayashi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
| | | | | | - Nusrat Iqbal
- Department of Surgery, Worcestershire Acute Hospitals NHS Trust, Worcester, UK
| | - Marietta Iacucci
- APC Microbiome Ireland, College of Medicine and Health, University College of Cork, Cork, Ireland
| | - Stefan Holubar
- Department of Colon & Rectal Surgery, Cleveland Clinic, Cleveland, OH, USA
| | - Jurij Hanzel
- Department of Gastroenterology, University Medical Centre Ljubljana, Ljubljana, Slovenia
- Department of of Internal Medicine, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - João Guedelha Sabino
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Javier P Gisbert
- Gastroenterology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa [IIS-Princesa], Universidad Autónoma de Madrid [UAM], Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBEREHD], Madrid, Spain
| | | | - Catarina Fidalgo
- Division of Gastroenterology, Hospital Beatriz Ângelo, Loures Division of Gastroenterology, Hospital da Luz, Lisboa, Portugal
| | - Pierre Ellu
- Division of Gastroenterology, Mater Dei Hospital, l-Msida, Malta
| | - Alaa El-Hussuna
- OpenSourceResearch Organization [OSRC.Network], Aalborg, Denmark
| | - Joline de Groof
- Colorectal Surgery, Royal Surrey NHS Foundation Trust, Guildford, UK
| | - Wladyslawa Czuber-Dochan
- Florence Nightingale Faculty of Nursing-Midwifery and Palliative Care, King's College London, London, UK
| | - María José Casanova
- Gastroenterology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa [IIS-Princesa], Universidad Autónoma de Madrid [UAM], Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBEREHD], Madrid, Spain
| | - Johan Burisch
- Gastrounit, Medical Division, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark
| | | | | | - Dominik Bettenworth
- CED Schwerpunktpraxis, Münster and Medical Faculty of the University of Münster, Münster, Germany
| | - Robert Battat
- Division of Gastroenterology, Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada
| | - Raja Atreya
- First Department of Medicine, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
| | - Mariangela Allocca
- IRCCS Hospital San Raffaele and University Vita-Salute San Raffaele, Gastroenterology and Endoscopy, Milan, Italy
| | - Manasi Agrawal
- Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Center for Molecular Prediction of Inflammatory Bowel Disease [PREDICT], Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark
| | - Tim Raine
- Department of Gastroenterology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Hannah Gordon
- Translational Gastroenterology and Liver Unit, Gastroenterology Office, University of Oxford, Oxford, UK
| | - Pär Myrelid
- Department of Surgery and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
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Khan SZ, Arline A, Williams KM, Lee MJ, Steinhagen E, Stein SL. The use of core descriptors from the ENiGMA code study in recent literature: a systematic review. Colorectal Dis 2024; 26:428-438. [PMID: 38296841 DOI: 10.1111/codi.16893] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Accepted: 01/10/2024] [Indexed: 02/02/2024]
Abstract
AIM The heterogeneity in data quality presented in studies regarding Crohn's anal fistula (CAF) limit extrapolation into clinical practice. The ENiGMA collaborators established a core descriptor set to standardize reporting of CAF. The aim of this work was to quantify the use of these descriptors in recent literature. METHOD We completed a systematic review of PubMed and the Cochrane Library, extracting publications from the past 10 years specific to the clinical interventions and outcomes of CAF, and reported in line with PRISMA guidance. Each article was assessed for inclusion of ENiGMA descriptors. The median number of descriptors per publication was evaluated along with the overall frequency of each individual descriptor. Use of ENiGMA descriptors was compared between medical and procedural publications. RESULTS Ninety publications were included. The median number of descriptors was 15 of 37; 16 descriptors were used in over half of the publications while 17 were used in fewer than a third. Descriptors were more frequently used in procedural (n = 16) than medical publications (n = 14) (p = 0.031). In procedural publications, eight descriptors were more frequently used including Faecal incontinence, Number of previous fistula interventions, Presence and severity of anorectal stenosis and Current proctitis. Medical publications were more likely to include Previous response to biological therapy and Duration and type of current course of biological therapy. CONCLUSION With many descriptors being used infrequently and variations between medical and procedural literature, the colorectal community should assess the need for all 37 descriptors.
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Affiliation(s)
- Saher-Zahra Khan
- University Hospitals Research in Surgical Outcomes and Effectiveness Center (UH-RISES), Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
- Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, USA
| | - Andrea Arline
- Case Western Reserve University School of Medicine, Cleveland, USA
| | | | - Matthew J Lee
- Academic Directorate of General Surgery, Sheffield Teaching Hospitals NHS FT, Sheffield, UK
- Department of Oncology and Metabolism, The Medical School, University of Sheffield, Sheffield, UK
| | - Emily Steinhagen
- University Hospitals Research in Surgical Outcomes and Effectiveness Center (UH-RISES), Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
- Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, USA
| | - Sharon L Stein
- University Hospitals Research in Surgical Outcomes and Effectiveness Center (UH-RISES), Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
- Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, USA
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Amor IB, Triantafyllou E, Temime V, Chenaitia H, Benamran D, Vanbiervliet G, Dagher I, Gugenheim J, Lainas P. Endoscopic Administration of Combined Autologous Mesenchymal Stem Cells and Platelet-Rich Plasma for the Treatment of Gastric Staple Line Leaks After Sleeve Gastrectomy. Obes Surg 2024; 34:106-113. [PMID: 38017329 DOI: 10.1007/s11695-023-06942-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Revised: 10/25/2023] [Accepted: 11/08/2023] [Indexed: 11/30/2023]
Abstract
BACKGROUND Gastric staple line leak treatment after laparoscopic sleeve gastrectomy (LSG) remains challenging. Regenerative medicine is gaining place in the accelerated treatment of damaged tissues. This study presents the first series of gastric leak treatment after LSG using endoscopic intragastric administration of combined autologous mesenchymal stem cells (MSC) and platelet-rich plasma (PRP). METHODS MSC-PRP harvesting and endoscopic administration techniques are described in detail. Data were prospectively gathered and analyzed. Primary endpoints were morbidity/mortality rates and fistula closure time. RESULTS Twelve patients (9 women, 3 men) were included. Median age was 41.5 years, median weight 105.5 kg and median BMI 38.9 kg/m2. Median time to gastric staple line leak detection was 10 days post-LSG. Median time between re-laparoscopy and MSC-PRP administration was 5 days. MSC-PRP endoscopic administration was successfully performed and tolerated by all patients, with median procedure duration of 27 min and minimal blood loss. Four postoperative complications were noted: two patients with increased tibial pain at tibial puncture site, one with tibial hematoma, and one with epigastric pain/dysphagia. Median length of hospital stay was 1 day. Gastric leak healing occurred after a median of 14 days, only two patients requiring a second MSC-PRP endoscopic injection. Median follow-up was 19 months, all patients being in good health at last contact. CONCLUSION Endoscopic administration of combined autologous MSC-PRP seems to be a good option for treatment of gastric leaks after sleeve gastrectomy. It is a challenging procedure that should be performed in specialized bariatric centers by expert bariatric surgeons and endoscopists after meticulous patient selection.
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Affiliation(s)
- Imed Ben Amor
- Department of Digestive Surgery, Archet II Hospital, Nice, France
- University of Nice-Sophia-Antipolis, Nice, France
- INSERM U1081, Nice, France
| | - Evangelia Triantafyllou
- Department of Minimally Invasive Digestive & Bariatric Surgery, Metropolitan Hospital, HEAL Academy, 9 Ethnarchou Makariou & 1 Venizelou Streets, Neo Faliro, 18547, Athens, Greece
| | - Victor Temime
- Department of Digestive Surgery, Archet II Hospital, Nice, France
| | - Hichem Chenaitia
- Department of Digestive Surgery, Archet II Hospital, Nice, France
| | - Dorith Benamran
- Department of Digestive Surgery, Archet II Hospital, Nice, France
| | | | - Ibrahim Dagher
- Department of Minimally Invasive Digestive Surgery, Antoine-Béclère Hospital, AP-HP, Clamart, France
- Paris-Saclay University, Orsay, France
| | - Jean Gugenheim
- Department of Digestive Surgery, Archet II Hospital, Nice, France
- University of Nice-Sophia-Antipolis, Nice, France
- INSERM U1081, Nice, France
| | - Panagiotis Lainas
- Department of Minimally Invasive Digestive & Bariatric Surgery, Metropolitan Hospital, HEAL Academy, 9 Ethnarchou Makariou & 1 Venizelou Streets, Neo Faliro, 18547, Athens, Greece.
- Department of Minimally Invasive Digestive Surgery, Antoine-Béclère Hospital, AP-HP, Clamart, France.
- Paris-Saclay University, Orsay, France.
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Rosevics L, Savio MC, Lima Júnior E, Ramos Júnior O. FISTULIZING PERIANAL CROHN'S DISEASE: IS THE PATIENT'S SEX A BURDEN? A SYSTEMATIC REVIEW. ARQUIVOS DE GASTROENTEROLOGIA 2023; 60:490-524. [PMID: 38018554 DOI: 10.1590/s0004-2803.230402023-28] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Accepted: 07/31/2023] [Indexed: 11/30/2023]
Abstract
BACKGROUND Fistulizing perianal Crohn's disease poses a treatment challenge, and researchers postulate that this phenotype in young male patients could have a worst outcome. OBJECTIVE Thus, the aim of this study was to assess whether sex influences the response to treatment for these patients. METHODS This systematic review (PROSPERO CRD42022319629) was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. We selected articles published in English, Spanish, Portuguese, and Italian between 2010 and 2020 in the PubMed and Science Direct databases. According to the PICO acronym, prospective studies in patients older than 18 years with the objective of treating fistulizing perianal Crohn's disease were selected. Studies in pediatric populations, retrospective, without treatment objectives, and that included only rectovaginal fistulas or a single sex were excluded. Study quality was assessed using the Cochrane risk of bias tool and Newcastle-Ottawa scale. RESULTS Of the 1887 articles found, 33 were included. Most studies used anti-TNF drugs as treatment (n=11). Ten studies had subgroup analyses; of them, the two studies reporting sex differences used infliximab and adalimumab as treatment and showed that women had a longer fistula closure time than men. CONCLUSION This systematic review showed that few data corroborate the difference between sexes in the treatment of fistulizing perianal Crohn's disease, possibly having a greater relationship with the phenotype. However, considering the lack of results, further studies with this objective and with standardization of fistulas and response assessment methods are needed.
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Tian CM, Zhang Y, Yang MF, Xu HM, Zhu MZ, Yao J, Wang LS, Liang YJ, Li DF. Stem Cell Therapy in Inflammatory Bowel Disease: A Review of Achievements and Challenges. J Inflamm Res 2023; 16:2089-2119. [PMID: 37215379 PMCID: PMC10199681 DOI: 10.2147/jir.s400447] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Accepted: 05/03/2023] [Indexed: 05/24/2023] Open
Abstract
Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a group of chronic inflammatory diseases of the gastrointestinal tract. Repeated inflammation can lead to complications, such as intestinal fistula, obstruction, perforation, and bleeding. Unfortunately, achieving durable remission and mucosal healing (MH) with current treatments is difficult. Stem cells (SCs) have the potential to modulate immunity, suppress inflammation, and have anti-apoptotic and pro-angiogenic effects, making them an ideal therapeutic strategy to target chronic inflammation and intestinal damage in IBD. In recent years, hematopoietic stem cells (HSCs) and adult mesenchymal stem cells (MSCs) have shown efficacy in treating IBD. In addition, numerous clinical trials have evaluated the efficiency of MSCs in treating the disease. This review summarizes the current research progress on the safety and efficacy of SC-based therapy for IBD in both preclinical models and clinical trials. We discuss potential mechanisms of SC therapy, including tissue repair, paracrine effects, and the promotion of angiogenesis, immune regulation, and anti-inflammatory effects. We also summarize current SC engineering strategies aimed at enhancing the immunosuppressive and regenerative capabilities of SCs for treating intestinal diseases. Additionally, we highlight current limitations and future perspectives of SC-related therapy for IBD.
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Affiliation(s)
- Cheng-Mei Tian
- Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, People’s Republic of China
- Department of Emergency, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, People’s Republic of China
| | - Yuan Zhang
- Department of Medical Administration, Huizhou Institute of Occupational Diseases Control and Prevention, Huizhou, Guangdong, People’s Republic of China
| | - Mei-Feng Yang
- Department of Hematology, Yantian District People’s Hospital, Shenzhen, Guangdong, People’s Republic of China
| | - Hao-Ming Xu
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China
| | - Min-Zheng Zhu
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China
| | - Jun Yao
- Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, People’s Republic of China
| | - Li-Sheng Wang
- Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, People’s Republic of China
| | - Yu-Jie Liang
- Department of Child and Adolescent Psychiatry, Shenzhen Kangning Hospital, Shenzhen, Guangdong, People’s Republic of China
| | - De-Feng Li
- Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, People’s Republic of China
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Coelho HRS, Neves SC, Menezes JNS, Antoniolli-Silva ACMB, Oliveira RJ. Cell therapy with adipose tissue-derived human stem cells in the urinary bladder improves detrusor contractility and reduces voiding residue. BRAZ J BIOL 2023; 83:e268540. [PMID: 37132740 DOI: 10.1590/1519-6984.268540] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Accepted: 02/27/2023] [Indexed: 05/04/2023] Open
Abstract
Detrusor hypocontractility (DH) is a disease without a gold standard treatment in traditional medicine. Therefore, there is a need to develop innovative therapies. The present report presents the case of a patient with DH who was transplanted with 2 x 106 adipose tissue-derived mesenchymal stem cells twice and achieved significant improvements in their quality of life. The results showed that cell therapy reduced the voiding residue from 1,800 mL to 800 mL, the maximum cystometric capacity from 800 to 550 mL, and bladder compliance from 77 to 36.6 mL/cmH2O. Cell therapy also increased the maximum flow from 3 to 11 mL/s, the detrusor pressure from 08 to 35 cmH2O, the urine volume from 267 to 524 mL and the bladder contractility index (BCI) value from 23 to 90. The International Continence on Incontinence Questionnaire - Short Form score decreased from 17 to 8. Given the above, it is inferred that the transplantation of adipose tissue-derived mesenchymal stem cells is an innovative and efficient therapeutic strategy for DH treatment and improves the quality of life of patients affected by this disease.
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Affiliation(s)
- H R S Coelho
- Universidade Federal do Mato Grosso do Sul - UFMS, Faculdade de Medicina - FAMED, Centro de Estudos em Células-Tronco, Terapia Celular e Genética Toxicológica - CeTroGen, Campo Grande, MS, Brasil
- Universidade Federal do Mato Grosso do Sul - UFMS, Faculdade de Medicina - FAMED, Programa de Pós-graduação em Saúde e Desenvolvimento na Região Centro-Oeste, Campo Grande, MS, Brasil
| | - S C Neves
- Universidade Federal do Mato Grosso do Sul - UFMS, Faculdade de Medicina - FAMED, Centro de Estudos em Células-Tronco, Terapia Celular e Genética Toxicológica - CeTroGen, Campo Grande, MS, Brasil
- Universidade Federal do Mato Grosso do Sul - UFMS, Faculdade de Medicina - FAMED, Programa de Pós-graduação em Saúde e Desenvolvimento na Região Centro-Oeste, Campo Grande, MS, Brasil
| | | | - A C M B Antoniolli-Silva
- Universidade Federal do Mato Grosso do Sul - UFMS, Faculdade de Medicina - FAMED, Centro de Estudos em Células-Tronco, Terapia Celular e Genética Toxicológica - CeTroGen, Campo Grande, MS, Brasil
- Universidade Federal do Mato Grosso do Sul - UFMS, Faculdade de Medicina - FAMED, Programa de Pós-graduação em Saúde e Desenvolvimento na Região Centro-Oeste, Campo Grande, MS, Brasil
| | - R J Oliveira
- Universidade Federal do Mato Grosso do Sul - UFMS, Faculdade de Medicina - FAMED, Centro de Estudos em Células-Tronco, Terapia Celular e Genética Toxicológica - CeTroGen, Campo Grande, MS, Brasil
- Universidade Federal do Mato Grosso do Sul - UFMS, Faculdade de Medicina - FAMED, Programa de Pós-graduação em Saúde e Desenvolvimento na Região Centro-Oeste, Campo Grande, MS, Brasil
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Rakowsky S, Papamichael K, Cheifetz AS. Choosing the right biologic for complications of inflammatory bowel disease. Expert Rev Gastroenterol Hepatol 2022; 16:235-249. [PMID: 35094628 DOI: 10.1080/17474124.2022.2036122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Accepted: 01/27/2022] [Indexed: 11/04/2022]
Abstract
INTRODUCTION Inflammatory bowel disease (IBD) is a chronic, inflammatory condition that involves the intestinal tract, and can also present with extra-intestinal manifestations (EIM). Choosing the right treatment for IBD is often nuanced and decisions can become even more complicated when a patient presents with or develops a complication of the disease. AREAS COVERED We aimed to provide an overview of the most common complications of IBD, specifically intestinal and EIM, and summarize the data regarding biologic therapy for treatment of these conditions. A comprehensive literature review was performed using PubMed and Medline databases to identify studies published in the English language relevant to the broad scope of this review. EXPERT OPINION There are still significant gaps in our understanding of the pathophysiology of IBD and its treatment, especially in regards to complications of the disease. As novel therapies continue to emerge for treatment of IBD, we feel concurrent examination of their impact on intestinal complications and EIM of IBD is important and should be a priority of future research.
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Affiliation(s)
- Shana Rakowsky
- Department of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA USA
| | - Konstantinos Papamichael
- Department of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA USA
| | - Adam S Cheifetz
- Department of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA USA
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An Affordable Approach of Mesenchymal Stem Cell Therapy in Treating Perianal Fistula Treatment. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2022; 1401:73-95. [DOI: 10.1007/5584_2022_716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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11
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Sebbagh AC, Rosenbaum B, Péré G, Alric H, Berger A, Wilhelm C, Gazeau F, Mathieu N, Rahmi G, Silva AKA. Regenerative medicine for digestive fistulae therapy: Benefits, challenges and promises of stem/stromal cells and emergent perspectives via their extracellular vesicles. Adv Drug Deliv Rev 2021; 179:113841. [PMID: 34175308 DOI: 10.1016/j.addr.2021.113841] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 05/29/2021] [Accepted: 06/15/2021] [Indexed: 12/11/2022]
Abstract
Despite current management strategies, digestive fistulae remain extremely debilitating complications associated with significant morbidity and mortality, generating a need to develop innovative therapies in these indications. A number of clinical trials and experimental studies have thus investigated the potential of stem/stromal cells (SCs) or SC-derived extracellular vesicles (EVs) administration for post-surgical and Crohn's-associated fistulae. This review summarizes the physiopathology and current standards-of-care for digestive fistulae, along with relevant evidence from animal and clinical studies regarding SC or EV treatment for post-surgical digestive fistulae. Additionally, existing preclinical models of fistulizing Crohn's disease and results of SC therapy trials in this indication will be presented. The optimal formulation and administration protocol of SC therapy products for gastrointestinal fistula treatment and the challenges for a widespread use of darvadstrocel (Alofisel) in clinical practice will be discussed. Finally, the potential advantages of EV therapy and the obstacles towards their clinical translation will be introduced.
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Affiliation(s)
- Anna C Sebbagh
- Laboratoire Matière et Systèmes Complexes (MSC), Université de Paris/CNRS (UMR 7057), Paris, France
| | - Boris Rosenbaum
- Laboratoire Imagerie de l'Angiogénèse, Plateforme d'Imagerie du Petit Animal, Inserm UMR970, Paris Cardiovascular Research Center, Paris, France
| | - Guillaume Péré
- Laboratoire Matière et Systèmes Complexes (MSC), Université de Paris/CNRS (UMR 7057), Paris, France; Laboratoire Imagerie de l'Angiogénèse, Plateforme d'Imagerie du Petit Animal, Inserm UMR970, Paris Cardiovascular Research Center, Paris, France; Department of Digestive Surgery, Esogastric Bariatric and Endocrinal Surgery Unit, Toulouse-Rangueil University Hospital, Toulouse, France
| | - Hadrien Alric
- Laboratoire Matière et Systèmes Complexes (MSC), Université de Paris/CNRS (UMR 7057), Paris, France; Laboratoire Imagerie de l'Angiogénèse, Plateforme d'Imagerie du Petit Animal, Inserm UMR970, Paris Cardiovascular Research Center, Paris, France; Department of Gastroenterology and Endoscopy, Hôpital Européen Georges Pompidou, Assistance Publique Hôpitaux de Paris, Paris, France
| | - Arthur Berger
- Laboratoire Imagerie de l'Angiogénèse, Plateforme d'Imagerie du Petit Animal, Inserm UMR970, Paris Cardiovascular Research Center, Paris, France
| | - Claire Wilhelm
- Laboratoire Matière et Systèmes Complexes (MSC), Université de Paris/CNRS (UMR 7057), Paris, France
| | - Florence Gazeau
- Laboratoire Matière et Systèmes Complexes (MSC), Université de Paris/CNRS (UMR 7057), Paris, France
| | - Noëlle Mathieu
- Human Health Department, SERAMED, LRMED, Institute for Radiological Protection and Nuclear Safety, Fontenay-aux-Roses, France
| | - Gabriel Rahmi
- Laboratoire Imagerie de l'Angiogénèse, Plateforme d'Imagerie du Petit Animal, Inserm UMR970, Paris Cardiovascular Research Center, Paris, France; Department of Gastroenterology and Endoscopy, Hôpital Européen Georges Pompidou, Assistance Publique Hôpitaux de Paris, Paris, France.
| | - Amanda K A Silva
- Laboratoire Matière et Systèmes Complexes (MSC), Université de Paris/CNRS (UMR 7057), Paris, France.
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Efficacy and safety of autologous adipose-derived stromal vascular fraction enriched with platelet-rich plasma in flap repair of transsphincteric cryptoglandular fistulas. Tech Coloproctol 2021; 25:1301-1309. [PMID: 34606026 PMCID: PMC8580893 DOI: 10.1007/s10151-021-02524-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 09/07/2021] [Indexed: 12/26/2022]
Abstract
Background Transanal advancement flap repair of transsphincteric fistulas is a sphincter-preserving procedure, which frequently fails, probably due to ongoing inflammation in the remaining fistula tract. Adipose-derived stromal vascular fraction (SVF) has immunomodulatory properties promoting wound healing and suppressing inflammation. Platelet-rich plasma (PRP) reinforces this biological effect. The aim of this study was to evaluate the efficacy and safety of autologous adipose-derived SVF enriched with PRP in flap repair of transsphincteric cryptoglandular fistulas. Methods A prospective cohort study was conducted including consecutive patients with transsphincteric cryptoglandular fistula in a tertiary referral center. During flap repair, SVF was obtained by lipoharvesting and mechanical fractionation of adipose tissue and combined with PRP was injected around the internal opening and into the fistulous wall. Endpoints were fistula healing at clinical examination and fistula closure on postoperative magnetic resonance imaging (MRI). Adverse events were documented. Results Forty-five patients with transsphincteric cryptoglandular fistula were included (29 males, median age 44 years [range 36–53 years]). In the total study population, primary fistula healing was observed in 38 patients (84%). Among the 42 patients with intestinal continuity at time of surgery, primary fistula healing was observed in 35 patients (84%). In one patient, the fistula recurred, resulting in a long-term healing rate of 82%. MRI, performed in 37 patients, revealed complete closure of the fistula tract in 33 (89.2%). In the other patients, the tract was almost completely obliterated by scar tissue. During follow-up, none of these patients showed clinical signs of recurrence. The postoperative course was uneventful, except for three cases; venous thromboembolism in one patient and bleeding under the flap, necessitating intervention in two patients. Conclusions Addition of autologous SVF enriched with PRP during flap repair is feasible, safe and might improve outcomes in patients with a transsphincteric cryptoglandular fistula. Trial registration Dutch Trial Register, Trial Number: NL8416, https://www.trialregister.nl/
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Tatsis D, Vasalou V, Kotidis E, Anestiadou E, Grivas I, Cheva A, Koliakos G, Venetis G, Pramateftakis MG, Ouzounidis N, Angelopoulos S. The Combined Use of Platelet-Rich Plasma and Adipose-Derived Mesenchymal Stem Cells Promotes Healing. A Review of Experimental Models and Future Perspectives. Biomolecules 2021; 11:1403. [PMID: 34680036 PMCID: PMC8533225 DOI: 10.3390/biom11101403] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 09/15/2021] [Accepted: 09/17/2021] [Indexed: 11/16/2022] Open
Abstract
Wound healing and tissue regeneration are a field of clinical medicine presenting high research interest, since various local and systematic factors can inhibit these processes and lead to an inferior result. New methods of healing enhancement constantly arise, which, however, require experimental validation before their establishment in everyday practice. Platelet-rich plasma (PRP) is a well-known autologous factor that promotes tissue healing in various surgical defects. PRP derives from the centrifugation of peripheral blood and has a high concentration of growth factors that promote healing. Recently, the use of adipose-derived mesenchymal stem cells (ADMSCs) has been thoroughly investigated as a form of wound healing enhancement. ADMSCs are autologous stem cells deriving from fat tissue, with a capability of differentiation in specific cells, depending on the micro-environment that they are exposed to. The aim of the present comprehensive review is to record the experimental studies that have been published and investigate the synergistic use of PRP and ADMSC in animal models. The technical aspects of experimentations, as well as the major results of each study, are discussed. In addition, the limited clinical studies including humans are also reported. Future perspectives are discussed, along with the limitations of current studies on the long-term follow up needed on efficacy and safety.
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Affiliation(s)
- Dimitris Tatsis
- Fourth Surgical Department, School of Medicine, Aristotle University of Thessaloniki, 57010 Thessaloniki, Greece; (V.V.); (E.K.); (E.A.); (M.-G.P.); (N.O.); (S.A.)
- Oral and Maxillofacial Surgery Department, School of Dentistry, Aristotle University of Thessaloniki, 57010 Thessaloniki, Greece;
| | - Varvara Vasalou
- Fourth Surgical Department, School of Medicine, Aristotle University of Thessaloniki, 57010 Thessaloniki, Greece; (V.V.); (E.K.); (E.A.); (M.-G.P.); (N.O.); (S.A.)
| | - Efstathios Kotidis
- Fourth Surgical Department, School of Medicine, Aristotle University of Thessaloniki, 57010 Thessaloniki, Greece; (V.V.); (E.K.); (E.A.); (M.-G.P.); (N.O.); (S.A.)
| | - Elissavet Anestiadou
- Fourth Surgical Department, School of Medicine, Aristotle University of Thessaloniki, 57010 Thessaloniki, Greece; (V.V.); (E.K.); (E.A.); (M.-G.P.); (N.O.); (S.A.)
| | - Ioannis Grivas
- Laboratory of Anatomy, Histology & Embryology, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece;
| | - Angeliki Cheva
- Department of Pathology, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece;
| | - Georgios Koliakos
- Department of Biochemistry, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece;
| | - Gregory Venetis
- Oral and Maxillofacial Surgery Department, School of Dentistry, Aristotle University of Thessaloniki, 57010 Thessaloniki, Greece;
| | - Manousos-George Pramateftakis
- Fourth Surgical Department, School of Medicine, Aristotle University of Thessaloniki, 57010 Thessaloniki, Greece; (V.V.); (E.K.); (E.A.); (M.-G.P.); (N.O.); (S.A.)
| | - Nikolaos Ouzounidis
- Fourth Surgical Department, School of Medicine, Aristotle University of Thessaloniki, 57010 Thessaloniki, Greece; (V.V.); (E.K.); (E.A.); (M.-G.P.); (N.O.); (S.A.)
| | - Stamatis Angelopoulos
- Fourth Surgical Department, School of Medicine, Aristotle University of Thessaloniki, 57010 Thessaloniki, Greece; (V.V.); (E.K.); (E.A.); (M.-G.P.); (N.O.); (S.A.)
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Kröner PT, Lee A, Farraye FA. Respiratory Tract Manifestations of Inflammatory Bowel Disease. Inflamm Bowel Dis 2021; 27:563-574. [PMID: 32448912 DOI: 10.1093/ibd/izaa112] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Indexed: 12/12/2022]
Abstract
Inflammatory bowel disease can manifest in many extraintestinal organ systems. The most frequently involved extraintestinal locations include the mucocutaneous, hepatobiliary, and ocular organ systems. The respiratory tract is less commonly involved and is therefore frequently overlooked. Consequently, it is believed that involvement of the respiratory tract in patients with inflammatory bowel disease is underreported. The pathogenesis is thought to be multifactorial, involving the common embryologic origin shared by the respiratory and luminal digestive tract, molecular mimicry, and immunologic interactions leading to immune-complex deposition in affected tissue. The spectrum of manifestations of the respiratory tract related to inflammatory bowel disease is broad. It not only includes direct involvement of the respiratory tract (ie, airways, interstitium, and pleura) but also can result as a consequence of systemic involvement such as in thromboembolic events. In addition, it may also be related to other conditions that affect the respiratory tract such as sarcoidosis and alpha-1 antitrypsin deficiency. Though some conditions related to respiratory tract involvement might be subclinical, others may have life-threatening consequences. It is critical to approach patients with suspected inflammatory bowel disease-related respiratory tract involvement in concert with pulmonology, infectious diseases, and any other pertinent experts, as treatments may require a multidisciplinary overlap of measures. Therefore, it is of paramount importance for the clinician to be aware of the array of respiratory tract manifestations of patients with inflammatory bowel disease, in addition to the possible spectrum of therapeutic measures.
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Affiliation(s)
- Paul T Kröner
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL
| | - Augustine Lee
- Division of Pulmonary, Allergy and Sleep Medicine, Mayo Clinic, Jacksonville, FL
| | - Francis A Farraye
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL
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Efficacy and Safety of Mesenchymal Stem/Stromal Cell Therapy for Inflammatory Bowel Diseases: An Up-to-Date Systematic Review. Biomolecules 2021; 11:biom11010082. [PMID: 33440772 PMCID: PMC7827559 DOI: 10.3390/biom11010082] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 12/31/2020] [Accepted: 01/06/2021] [Indexed: 12/12/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gut that can lead to severe gastrointestinal symptoms, malnutrition, and complications such as fistulas and cancer. Mesenchymal stem/stromal cells (MSCs) are being investigated as a novel therapy for IBD and have been demonstrated to be safe and effective for perianal fistulizing Crohn’s disease (PFCD). This systematic review aims to present the most recent studies on the safety and efficacy of MSC therapy in IBD. A detailed search strategy of clinical trials on MSCs and IBD was performed on PubMed, with 32 studies selected for inclusion in this review. The newest studies on local MSC injection for PFCD continue to support long-term efficacy while maintaining a favorable safety profile. The evidence for systemic MSC infusion in luminal IBD remains mixed due to marked methodological heterogeneity and unclear safety profiles. Although further studies are needed to better establish the role of this novel treatment modality, MSCs are proving to be a very exciting addition to the limited therapies available for IBD.
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Cao Y, Su Q, Zhang B, Shen F, Li S. Efficacy of stem cells therapy for Crohn's fistula: a meta-analysis and systematic review. Stem Cell Res Ther 2021; 12:32. [PMID: 33413661 PMCID: PMC7792029 DOI: 10.1186/s13287-020-02095-7] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Accepted: 12/10/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Fistulas have puzzled us all the time and stem cell therapy for it is still in its infancy. We conducted a meta-analysis and systematic review to evaluate the efficacy of stem cells and its potential mechanisms in the management of Crohn's fistula. METHODS Electronic databases were searched comprehensively for studies reporting the efficacy and safety of stem cells in patients with any form of Crohn's fistula. A random-effects model was used, and all outcomes were calculated by SPSS 24.0. RESULTS Twenty-nine articles with 1252 patients were included. It showed that stem cell group had a higher rate of fistula healing compared to placebo group in patients of Crohn's fistula (61.75% vs 40.46%, OR 2.21, 95% CI 1.19 to 4.11, P < 0.05). 3 × 107 cells/mL stem cell (SC) group had an advantage in fistula healing rate with 71.0% compared to other doses group of stem cells (RR 1.3, 95% CI 0.76 to 2.22). And the healing rates of patients with perianal and transsphincteric fistulas (77.95%, 76.41%) were higher than those with rectovaginal fistulas. It was an amazing phenomenon that CDAI and PDAI scores occurred an obviously transient rise with the use of stem cells after 1 month (both of P < 0.05), while they returned to the baseline level by giving stem cells 3 months later. Furthermore, the incidence rate of treatment-related adverse events in the stem cell group was significantly lower than in the placebo group (RR 0.58, 95% CI 0.30 to 1.14). CONCLUSIONS Our study has highlighted that stem cells was a promising method in the treatment of Crohn's fistula based on its higher efficacy and lower incidence of adverse events, especially ADSCs and Cx601. While it also needs more clinical and pre-clinical studies to strengthen evidences in the future.
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Affiliation(s)
- Yantian Cao
- Department of Gastroenterology, The Third Affiliated Hospital of Xinxiang Medical University, Hua Lan Avenue, Xinxiang, 453003, Henan Province, China
| | - Qi Su
- Department of General surgery, The Third Affiliated Hospital of Xinxiang Medical University, Hua Lan Avenue, Xinxiang, 453003, Henan Province, China
| | - Bangjie Zhang
- Department of Gastroenterology, The Third Affiliated Hospital of Xinxiang Medical University, Hua Lan Avenue, Xinxiang, 453003, Henan Province, China
| | - Fangfang Shen
- The Key Laboratory for Tumor Translational Medicine, The Third Affiliated Hospital of Xinxiang Medical University, Hua Lan Avenue, Xinxiang, 453003, Henan Province, China
| | - Shaoshan Li
- Department of General surgery, The Third Affiliated Hospital of Xinxiang Medical University, Hua Lan Avenue, Xinxiang, 453003, Henan Province, China.
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Cassinotti A, Passamonti F, Segato S. CELL THERAPY IN INFLAMMATORY BOWEL DISEASE. Pharmacol Res 2021; 163:105247. [PMID: 33069755 DOI: 10.1016/j.phrs.2020.105247] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Revised: 10/06/2020] [Accepted: 10/07/2020] [Indexed: 12/14/2022]
Abstract
In recent years, cell-based therapies have been explored in various immune-mediated inflammatory diseases, including inflammatory bowel disease (IBD). Cell therapy is the process of introducing new cells into an organism or tissue in order to treat a disease. The most studied cellular treatment in IBD was "stem cells-based therapy", which was explored according to different protocols in terms of type of donors, stem cells sources, study design and clinical endpoints. More recently, preliminary studies have also described the clinical use of "regulatory cells", which include T-reg and Tr1 cells, and "tolerogenic" dendritic cells. Finally, induced pluripotent stem cells are the subject of an intensive preclinical research program on animal models, including those related to colitis.
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Affiliation(s)
| | | | - Sergio Segato
- Gastroenterology Unit, ASST Sette Laghi, Varese Italy
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Hossein-Khannazer N, Torabi S, Hosseinzadeh R, Shahrokh S, Asadzadeh Aghdaei H, Memarnejadian A, Kadri N, Vosough M. Novel cell-based therapies in inflammatory bowel diseases: the established concept, promising results. Hum Cell 2021; 34:1289-1300. [PMID: 34057700 PMCID: PMC8165675 DOI: 10.1007/s13577-021-00560-w] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2021] [Accepted: 05/26/2021] [Indexed: 02/05/2023]
Abstract
Inflammatory bowel diseases (IBDs) are chronic and relapsing disorders that affect the quality of life in many individuals around the world. Over the past few years, the prevalence of IBDs is substantially rising which might pose a considerable social and economic burden on health systems. Progresses in the management of chronic inflammatory diseases lead to prolonged remission phase and decreased hospitalization rate. However, during treatment, many patients become refractory to conventional therapies. Recently, advanced approaches using somatic cell therapy medicinal products (SCTMPs) including immune and stem cell-based therapies have drawn many researchers' attentions. Promising results from recent trials, alongside with the emerging market indicated that these therapeutic approaches could be an alternative and promising treatment to conventional therapies. In this review, we will discuss recent advances in cell-based therapies, which have been developed for treatment of IBDs. In addition, the global emerging market and the novel products in this field are highlighted.
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Affiliation(s)
- Nikoo Hossein-Khannazer
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shukoofeh Torabi
- Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Ramin Hosseinzadeh
- Department of Medical Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Shabnam Shahrokh
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamid Asadzadeh Aghdaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Nadir Kadri
- Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.
| | - Massoud Vosough
- Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
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19
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de la Portilla F, Jiménez-Salido A, Araujo-Miguez A, Maestre-Sanchez MV, Reyes-Diaz ML, Ramallo-Solís I, Ramos-Fernández M, Vázquez-Monchul JM, García-Cabrera AM, Jimenez-Rodríguez RM, Díaz-Pavón JM, Padillo-Ruiz FJ. Autologous Platelet-Rich Plasma in the Treatment of Perianal Fistula in Crohn's Disease. J Gastrointest Surg 2020; 24:2814-2821. [PMID: 31823319 DOI: 10.1007/s11605-019-04480-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2019] [Accepted: 11/17/2019] [Indexed: 01/31/2023]
Abstract
AIM To assess clinical healing in patients with perianal Crohn's disease with local intrafistular injection of autologous platelet-rich plasma. METHOD The pilot study was conducted at a single centre between January 2013 and December 2015. Autologous platelet-rich plasma was prepared in platelet-rich and platelet-poor fractions for local intrafistular injection in patients with proven, established perianal Crohn's disease. Patients were permitted biological therapies, and the Perianal Crohn's Disease Activity Index was recorded. Patients were followed for 48 weeks for clinical signs of healing (complete, partial or non-healing), monitoring fistula drainage, closure and epithelialization. RESULTS The study included 29 patients (19 males; mean age 38 ± 12.8 years) with four exclusions in the operating room because surgery was not indicated and four lost to follow-up. Five adverse events were recorded, with two requiring the drainage of abscess collections. Of the 21 patients assessable at 24 weeks, there was complete healing, partial healing and non-healing in 7 (33.3%), 8 (38.1%) and 6 (28.6%) patients, respectively. By 48 weeks, there was complete healing, partial healing and non-healing in 6 (40%), 6 (40%) and 3 (20%) patients, respectively, with a reduction in the number of visible external fistula openings at both time points (P = 0.021). By the end of the study, there was a higher trend of healing if biological therapies were continued (85.7% with biologics vs. 75% without, P = 0.527), but there were no statistically significant differences and no differences in the Perianal Crohn's Disease Activity Index. CONCLUSION Autologous platelet-rich plasma is safe in patients with perianal Crohn's disease, with an acceptable healing rate over a medium-term follow-up, particularly if biological therapies are used concomitantly.
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Affiliation(s)
- F de la Portilla
- Coloproctology Unit Clinical Management Unit of General and Gastrointestinal Surgery Division Seville, Biomedical Research Institute (IBIS), Avenida Manuel Siurot s/n, 41013, Seville, Spain.
| | - A Jiménez-Salido
- Coloproctology Unit Clinical Management Unit of General and Gastrointestinal Surgery Division Seville, Biomedical Research Institute (IBIS), Avenida Manuel Siurot s/n, 41013, Seville, Spain
| | - A Araujo-Miguez
- University Hospital Virgen del Rocio/CSIC University of Seville, SPAIN Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain
| | - M V Maestre-Sanchez
- Coloproctology Unit Clinical Management Unit of General and Gastrointestinal Surgery Division Seville, Biomedical Research Institute (IBIS), Avenida Manuel Siurot s/n, 41013, Seville, Spain
| | - M L Reyes-Diaz
- Coloproctology Unit Clinical Management Unit of General and Gastrointestinal Surgery Division Seville, Biomedical Research Institute (IBIS), Avenida Manuel Siurot s/n, 41013, Seville, Spain
| | - I Ramallo-Solís
- Coloproctology Unit Clinical Management Unit of General and Gastrointestinal Surgery Division Seville, Biomedical Research Institute (IBIS), Avenida Manuel Siurot s/n, 41013, Seville, Spain
| | - M Ramos-Fernández
- Coloproctology Unit Clinical Management Unit of General and Gastrointestinal Surgery Division Seville, Biomedical Research Institute (IBIS), Avenida Manuel Siurot s/n, 41013, Seville, Spain
- University Hospital Virgen del Rocio/CSIC University of Seville, SPAIN Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain
| | - J M Vázquez-Monchul
- Coloproctology Unit Clinical Management Unit of General and Gastrointestinal Surgery Division Seville, Biomedical Research Institute (IBIS), Avenida Manuel Siurot s/n, 41013, Seville, Spain
| | - A M García-Cabrera
- Coloproctology Unit Clinical Management Unit of General and Gastrointestinal Surgery Division Seville, Biomedical Research Institute (IBIS), Avenida Manuel Siurot s/n, 41013, Seville, Spain
| | - R M Jimenez-Rodríguez
- Coloproctology Unit Clinical Management Unit of General and Gastrointestinal Surgery Division Seville, Biomedical Research Institute (IBIS), Avenida Manuel Siurot s/n, 41013, Seville, Spain
| | - J M Díaz-Pavón
- Coloproctology Unit Clinical Management Unit of General and Gastrointestinal Surgery Division Seville, Biomedical Research Institute (IBIS), Avenida Manuel Siurot s/n, 41013, Seville, Spain
| | - F J Padillo-Ruiz
- Coloproctology Unit Clinical Management Unit of General and Gastrointestinal Surgery Division Seville, Biomedical Research Institute (IBIS), Avenida Manuel Siurot s/n, 41013, Seville, Spain
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Gallo G, Tiesi V, Fulginiti S, De Paola G, Vescio G, Sammarco G. Mesenchymal Stromal Cell Therapy in the Management of Perianal Fistulas in Crohn's Disease: An Up-To-Date Review. MEDICINA (KAUNAS, LITHUANIA) 2020; 56:563. [PMID: 33121049 PMCID: PMC7692376 DOI: 10.3390/medicina56110563] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Revised: 10/19/2020] [Accepted: 10/26/2020] [Indexed: 12/12/2022]
Abstract
Crohn's Disease (CD) is a chronic inflammatory disorder that potentially involves the entire gastrointestinal tract. Perianal fistulizing CD (pCD) is a serious and frequent complication associated with significant morbidities and a heavy negative impact on quality of life. The aim of CD treatment is to induce and maintain disease remission and to promote mucosal repair. Unfortunately, even the best therapeutic regimens in pCD do not have long-term efficacy and cause a significant number of side effects. Therefore, it is mandatory to study new therapeutical options such as the use of mesenchymal stromal cells (MSCs). These cells promote tissue repair via the induction of immunomodulation. The present review aims to analyze the existing updated scientific literature on MSCs adoption in the treatment of pCD to evaluate its efficacy and safety and to compare the use of bone marrow and adipose tissue derived MSCs, type of administration, and dose required for recovery.
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Affiliation(s)
- Gaetano Gallo
- Department of Medical and Surgical Sciences, University of Catanzaro, Viale Europa, 88100 Catanzaro, Italy; (V.T.); (S.F.); (G.D.P.); (G.V.)
| | - Vincenzo Tiesi
- Department of Medical and Surgical Sciences, University of Catanzaro, Viale Europa, 88100 Catanzaro, Italy; (V.T.); (S.F.); (G.D.P.); (G.V.)
| | - Serena Fulginiti
- Department of Medical and Surgical Sciences, University of Catanzaro, Viale Europa, 88100 Catanzaro, Italy; (V.T.); (S.F.); (G.D.P.); (G.V.)
| | - Gilda De Paola
- Department of Medical and Surgical Sciences, University of Catanzaro, Viale Europa, 88100 Catanzaro, Italy; (V.T.); (S.F.); (G.D.P.); (G.V.)
| | - Giuseppina Vescio
- Department of Medical and Surgical Sciences, University of Catanzaro, Viale Europa, 88100 Catanzaro, Italy; (V.T.); (S.F.); (G.D.P.); (G.V.)
| | - Giuseppe Sammarco
- Department of Health Sciences, University of Catanzaro, Viale Europa, 88100 Catanzaro, Italy;
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Stem and Progenitor Cells in the Pathogenesis and Treatment of Digestive Diseases. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2020; 1201:125-157. [PMID: 31898785 DOI: 10.1007/978-3-030-31206-0_7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The global epidemic of chronic degenerative diseases expands rapidly. The pathogenesis of these noncommunicable disorders revolves around innate immunity, microbiome, and stem cell alterations. Understanding the mechanisms behind stem cell biology and their regulatory pathways is a key to understanding the origin of human disease. Stem cells are involved in tissue and organ damage and regeneration. The evidence is mounting that not only eukaryotic cells but also gut microbiota may release extracellular microvesicles that are absorbed from the gut into the portal and systemic circulation. Linking the fields of stem cells, innate immunity and microbiome research opens up new avenues to develop novel diagnostic (e.g., biomarkers), therapeutic (e.g., microbiome modulation, stem cell-based medicines), and prognostic (personalized diets) tools. In this chapter, we present the short overview of various stem and progenitor cells of adult tissues circulating in peripheral blood and their role in the pathogenesis and treatment of digestive diseases. We also briefly discuss the role of host-stem cell-microbial interactions as a new frontier of research in gastroenterology.
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22
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Bernardi L, Santos CHMD, Pinheiro VAZ, Oliveira RJ, Antoniolli-Silva ACMB. TRANSPLANTATION OF ADIPOSE-DERIVED MESENCHYMAL STEM CELLS IN REFRACTORY CROHN'S DISEASE: SYSTEMATIC REVIEW. ACTA ACUST UNITED AC 2019; 32:e1465. [PMID: 31859918 PMCID: PMC6918761 DOI: 10.1590/0102-672020190001e1465] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Accepted: 04/09/2019] [Indexed: 12/19/2022]
Abstract
Background: Crohn’s disease is a pathological condition that has different options of
treatment, but there are patients who need other therapeutic approach, such
as the use of adipose-derived mesenchymal stem cells. Aim: Systematic literature review to determine the different ways of
adipose-derived mesenchymal stem cells administration in humans with luminal
refractory and perianal fistulizing Crohn’s disease. Methods: It was conducted a search for articles (from 2008 to 2018) on PubMed and
ScienceDirect databases using the keywords Crohn’s disease, fistulizing
Crohn’s disease, luminal Crohn’s disease and transplantation of mesenchymal
stem cells or mesenchymal stem cells or stromal cells. Thirteen publications
were selected for analysis. Results: Only one study referred to the luminal Crohn´s disease. The number of cells
administered was variable, occurring mainly through subcutaneous adipose
tissue by liposuction. It could be highlighted the autologous transplant
with exclusive infusion of mesenchymal stem cells. The procedures involved
in pre-transplant were mainly curettage, setons placement and stitching with
absorbable suture, and conducting tests and drug treatment for luminal
Crohn´s disease. During transplant, the injection of mesenchymal stem cells
across the fistula path during the transplant was mainly on the intestinal
tract wall. Conclusion: Although the use of mesenchymal stem cells is promising, the transplant on
the luminal region should be more investigated. The injection of mesenchymal
stem cells, exclusively, is more explored when compared to treatment with
other products. The preparation of the fistulizing tract and the location of
cell transplantation involve standardized health care in most studies.
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Affiliation(s)
- Luana Bernardi
- Postgraduate Program in Health and Development in the Center-West Region, Faculty of Medicine, Campo Grande, MS, Brazil
| | - Carlos Henrique Marques Dos Santos
- Coloproctology Department, Maria Aparecida Pedrossian University Hospital, Federal University of Mato Grosso do Sul, Campo Grande, MS, Brazil
| | | | - Rodrigo Juliano Oliveira
- Postgraduate Program in Health and Development in the Center-West Region, Faculty of Medicine, Campo Grande, MS, Brazil.,Stem Cell Study Center, Cell Therapy and Toxicological Genetics, Maria Aparecida Pedrossian University Hospital, Campo Grande, MS, Brazil
| | - Andreia Conceição Milan Brochado Antoniolli-Silva
- Postgraduate Program in Health and Development in the Center-West Region, Faculty of Medicine, Campo Grande, MS, Brazil.,Stem Cell Study Center, Cell Therapy and Toxicological Genetics, Maria Aparecida Pedrossian University Hospital, Campo Grande, MS, Brazil
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23
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Advances in Perianal Disease Associated with Crohn's Disease-Evolving Approaches. Gastrointest Endosc Clin N Am 2019; 29:515-530. [PMID: 31078250 DOI: 10.1016/j.giec.2019.02.011] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Perianal diseases, common complications of Crohn's disease, are difficult to diagnose/manage. Patients with perianal Crohn's disease suffer from persistent pain and drainage, recurrent perianal sepsis, impaired quality of life, and financial burden. Conventional medical and surgical therapies carry risk of infection, myelosuppression, incontinence, disease recurrence. Although the phenotype of Crohn's disease has been extensively studied, reported outcomes are inconsistent. Endoanal ultrasonography is also becoming popular because of low cost and ability to acquire images in real time. Emerging management strategies for treatment including laser therapy, local injection of agents, use of hyperbaric oxygen, and stem cell therapy, have demonstrated efficacy.
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Quera R, Simian D, Pizarro G, Lubascher J, Kronberg U, Ibáñez P, Flores L, Figueroa C. Desarrollo de investigación y academia a partir de la labor clínica: Experiencia de un Programa de Enfermedad Inflamatoria Intestinal. REVISTA MÉDICA CLÍNICA LAS CONDES 2019. [DOI: 10.1016/j.rmclc.2018.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/07/2022] Open
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25
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Turse EP, Dailey FE, Naseer M, Partyka EK, Bragg JD, Tahan V. Stem cells for luminal, fistulizing, and perianal inflammatory bowel disease: a comprehensive updated review of the literature. Stem Cells Cloning 2018; 11:95-113. [PMID: 30568468 PMCID: PMC6267708 DOI: 10.2147/sccaa.s135414] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Much research has been performed over the last decade on stem cell therapy as treatment for patients with inflammatory bowel disease. Hematopoietic and mesenchymal stem cells, both allogeneic (from someone else) and autologous (from own patient), have been studied with safe and efficacious results in the majority of patients treated for luminal, perianal, and/or fistulizing disease. Here in this review, we highlight all human trials that have been conducted utilizing stem cell therapy treatment in patients with inflammatory bowel disease.
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Affiliation(s)
- Erica P Turse
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Missouri Health Center, Columbia, MO 65212, USA,
| | - Francis E Dailey
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Missouri Health Center, Columbia, MO 65212, USA,
| | - Maliha Naseer
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Missouri Health Center, Columbia, MO 65212, USA,
| | - Edward K Partyka
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Missouri Health Center, Columbia, MO 65212, USA,
| | - Jack D Bragg
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Missouri Health Center, Columbia, MO 65212, USA,
| | - Veysel Tahan
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Missouri Health Center, Columbia, MO 65212, USA,
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Álvarez JP, Coloma R, Leiva A, Berry M, Urrutia L, Yañez S, Galecio J, Ramos G, Cárcamo M, Fernández A, Guerrero M. Efecto de ketamina intraoperatoria sobre consumo de morfina durante 24 horas postoperatorias de pacientes obesos sometidos a gastrectomía en manga por videolaparoscopía. Ensayo Clínico Controlado Aleatorizado. REVISTA MÉDICA CLÍNICA LAS CONDES 2018. [DOI: 10.1016/j.rmclc.2018.10.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
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27
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Ibáñez P, Quera R, Lubascher J, Figueroa C, Pizarro G, Kronberg U, Flores L, Simian D. Algoritmos de tratamiento de la enfermedad de Crohn desde una experiencia local. REVISTA MÉDICA CLÍNICA LAS CONDES 2018. [DOI: 10.1016/j.rmclc.2018.07.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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28
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Turse EP, Dailey FE, Naseer M, Partyka EK, Tahan V. One more chance of fistula healing in inflammatory bowel disease: Stem cell therapy. World J Clin Cases 2018; 6:493-500. [PMID: 30397605 PMCID: PMC6212615 DOI: 10.12998/wjcc.v6.i12.493] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2018] [Revised: 08/09/2018] [Accepted: 08/28/2018] [Indexed: 02/05/2023] Open
Abstract
Patients with fistulizing inflammatory bowel disease are traditionally difficult to treat. This patient population often experiences delayed or insufficient healing of fistulas using current standard regimens including antibiotics, immunomodulators, anti-tumor necrosis factor-α drug, placement of setons, and surgical repair. Several studies over the last ten to fifteen years have been conducted using stem cell therapies with promising results in this patient population. These studies show stem cell therapy in fistulizing disease to be successful in healing between 60%-88% compared to currently 50% with infliximab. Moreover, remission was seen 24 wk to 52 wk in these studies. Further research with a multi-approach treatment using medications, stem cell therapy, and surgical interventions will likely be the future of this innovative treatment approach.
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Affiliation(s)
- Erica P Turse
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Missouri Health Center, Columbia, MO 65212, United States
| | - Francis E Dailey
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Missouri Health Center, Columbia, MO 65212, United States
| | - Maliha Naseer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Missouri Health Center, Columbia, MO 65212, United States
| | - Edward K Partyka
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Missouri Health Center, Columbia, MO 65212, United States
| | - Veysel Tahan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Missouri Health Center, Columbia, MO 65212, United States
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Bacakova L, Zarubova J, Travnickova M, Musilkova J, Pajorova J, Slepicka P, Kasalkova NS, Svorcik V, Kolska Z, Motarjemi H, Molitor M. Stem cells: their source, potency and use in regenerative therapies with focus on adipose-derived stem cells - a review. Biotechnol Adv 2018; 36:1111-1126. [PMID: 29563048 DOI: 10.1016/j.biotechadv.2018.03.011] [Citation(s) in RCA: 366] [Impact Index Per Article: 52.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2018] [Revised: 03/12/2018] [Accepted: 03/15/2018] [Indexed: 02/08/2023]
Abstract
Stem cells can be defined as units of biological organization that are responsible for the development and the regeneration of organ and tissue systems. They are able to renew their populations and to differentiate into multiple cell lineages. Therefore, these cells have great potential in advanced tissue engineering and cell therapies. When seeded on synthetic or nature-derived scaffolds in vitro, stem cells can be differentiated towards the desired phenotype by an appropriate composition, by an appropriate architecture, and by appropriate physicochemical and mechanical properties of the scaffolds, particularly if the scaffold properties are combined with a suitable composition of cell culture media, and with suitable mechanical, electrical or magnetic stimulation. For cell therapy, stem cells can be injected directly into damaged tissues and organs in vivo. Since the regenerative effect of stem cells is based mainly on the autocrine production of growth factors, immunomodulators and other bioactive molecules stored in extracellular vesicles, these structures can be isolated and used instead of cells for a novel therapeutic approach called "stem cell-based cell-free therapy". There are four main sources of stem cells, i.e. embryonic tissues, fetal tissues, adult tissues and differentiated somatic cells after they have been genetically reprogrammed, which are referred to as induced pluripotent stem cells (iPSCs). Although adult stem cells have lower potency than the other three stem cell types, i.e. they are capable of differentiating into only a limited quantity of specific cell types, these cells are able to overcome the ethical and legal issues accompanying the application of embryonic and fetal stem cells and the mutational effects associated with iPSCs. Moreover, adult stem cells can be used in autogenous form. These cells are present in practically all tissues in the organism. However, adipose tissue seems to be the most advantageous tissue from which to isolate them, because of its abundancy, its subcutaneous location, and the need for less invasive techniques. Adipose tissue-derived stem cells (ASCs) are therefore considered highly promising in present-day regenerative medicine.
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Affiliation(s)
- Lucie Bacakova
- Department of Biomaterials and Tissue Engineering, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220 Prague, 4-Krc, Czech Republic.
| | - Jana Zarubova
- Department of Biomaterials and Tissue Engineering, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220 Prague, 4-Krc, Czech Republic
| | - Martina Travnickova
- Department of Biomaterials and Tissue Engineering, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220 Prague, 4-Krc, Czech Republic
| | - Jana Musilkova
- Department of Biomaterials and Tissue Engineering, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220 Prague, 4-Krc, Czech Republic
| | - Julia Pajorova
- Department of Biomaterials and Tissue Engineering, Institute of Physiology of the Czech Academy of Sciences, Videnska 1083, 14220 Prague, 4-Krc, Czech Republic
| | - Petr Slepicka
- Department of Solid State Engineering, University of Chemistry and Technology Prague, Technicka 5, 166 28 Prague, 6-Dejvice, Czech Republic
| | - Nikola Slepickova Kasalkova
- Department of Solid State Engineering, University of Chemistry and Technology Prague, Technicka 5, 166 28 Prague, 6-Dejvice, Czech Republic
| | - Vaclav Svorcik
- Department of Solid State Engineering, University of Chemistry and Technology Prague, Technicka 5, 166 28 Prague, 6-Dejvice, Czech Republic
| | - Zdenka Kolska
- Faculty of Science, J.E. Purkyne University, Ceske mladeze 8, 400 96 Usti nad Labem, Czech Republic
| | - Hooman Motarjemi
- Clinic of Plastic Surgery, Faculty Hospital Na Bulovce, Budinova 67/2, 180 81 Prague, 8-Liben, Czech Republic
| | - Martin Molitor
- Clinic of Plastic Surgery, Faculty Hospital Na Bulovce, Budinova 67/2, 180 81 Prague, 8-Liben, Czech Republic
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