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Alric H, Mathieu N, Sebbagh A, Peré G, Demarquay C, Cronemberger A, Berger A, Marcel B, Wilhelm C, Gazeau F, Mariani A, Karoui M, Clément O, Araujo-Filho I, Silva AKA, Rahmi G. Thermoresponsive gel embedding extracellular vesicles from adipose stromal cells improves the healing of colonic anastomoses following irradiation in rats. Commun Biol 2024; 7:1673. [PMID: 39702754 DOI: 10.1038/s42003-024-07364-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Accepted: 12/04/2024] [Indexed: 12/21/2024] Open
Abstract
Anastomotic leak occurrence is a severe complication after colorectal surgery. Considering the difficulty of treating these leaks and their impact on patient care, there is a strong need for an efficient prevention strategy. We evaluated a combination of extracellular vesicles (EVs) from rat adipose-derived stromal cells with a thermoresponsive gel, Pluronic® F127 (PF-127) to prevent anastomotic leaks. The pro-regenerative and immunomodulatory potencies of EVs are assessed in vitro. In vivo efficacy are assessed in rat with a colonic anastomosis model after irradiation. Endoscopic, anatomical and histological data show a consistent effect of EVs + gel on the healing of colonic anastomosis. These results are illustrated by a smaller anastomotic ulcer size, less fibrosis and less inflammatory infiltrations in the EVs + gel group. This multi-modal investigation is the first to point-out the translational potential of EVs combined with PF-127 for the healing of high-risk colorectal anastomosis.
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Affiliation(s)
- Hadrien Alric
- Laboratoire de Recherche en Imagerie du Vivant, PARCC, INSERM U970, Université Paris Cité, Paris, France.
- Service d'Hépato-Gastro-Entérologie et Endoscopies Digestives, Hôpital Européen Georges Pompidou, APHP.Centre-Université Paris Cité, Paris, France.
| | - Noëlle Mathieu
- Laboratoire de Radiobiologie des Expositions Médicales, Institut de Radioprotection et de Sureté Nucléaire, Fontenay-Aux-Roses, France
| | - Anna Sebbagh
- Laboratoire Matière et Systèmes Complexes, CNRS, UMR 7057, Université Paris Cité, Paris, France
| | - Guillaume Peré
- Laboratoire de Recherche en Imagerie du Vivant, PARCC, INSERM U970, Université Paris Cité, Paris, France
- Service de Chirurgie Digestive, Centre-Hospitalo-Universitaire Toulouse-Rangueil, Toulouse, France
| | - Christelle Demarquay
- Laboratoire de Radiobiologie des Expositions Médicales, Institut de Radioprotection et de Sureté Nucléaire, Fontenay-Aux-Roses, France
| | - André Cronemberger
- Laboratoire Matière et Systèmes Complexes, CNRS, UMR 7057, Université Paris Cité, Paris, France
| | - Arthur Berger
- Laboratoire de Recherche en Imagerie du Vivant, PARCC, INSERM U970, Université Paris Cité, Paris, France
- Service d'Hépato-Gastroentérologie et Oncologie Digestive, Centre-Hospitalo-Universitaire Bordeaux, Bordeaux, France
| | - Benjamin Marcel
- Laboratoire Matière et Systèmes Complexes, CNRS, UMR 7057, Université Paris Cité, Paris, France
| | - Claire Wilhelm
- Laboratoire PhysicoChimie Curie, Institut Curie, PSL Research University-Sorbonne Université-CNRS, Paris, France
| | - Florence Gazeau
- Laboratoire Matière et Systèmes Complexes, CNRS, UMR 7057, Université Paris Cité, Paris, France
| | - Antoine Mariani
- Laboratoire de Recherche en Imagerie du Vivant, PARCC, INSERM U970, Université Paris Cité, Paris, France
- Service de Chirurgie Digestive, Hôpital Européen Georges Pompidou, Assistance Publique Hôpitaux de Paris, Paris, France
| | - Mehdi Karoui
- Laboratoire de Recherche en Imagerie du Vivant, PARCC, INSERM U970, Université Paris Cité, Paris, France
- Service de Chirurgie Digestive, Hôpital Européen Georges Pompidou, Assistance Publique Hôpitaux de Paris, Paris, France
| | - Olivier Clément
- Laboratoire de Recherche en Imagerie du Vivant, PARCC, INSERM U970, Université Paris Cité, Paris, France
- Service d'Imagerie, Hôpital Européen Georges Pompidou, Assistance Publique Hôpitaux de Paris, Paris, France
| | - Irami Araujo-Filho
- Department of Surgery, Federal University of Rio Grande do Norte. Institute of Teaching, Research, and Innovation, Liga Contra o Cancer, Natal, Brazil
| | - Amanda K A Silva
- Laboratoire Matière et Systèmes Complexes, CNRS, UMR 7057, Université Paris Cité, Paris, France
| | - Gabriel Rahmi
- Laboratoire de Recherche en Imagerie du Vivant, PARCC, INSERM U970, Université Paris Cité, Paris, France
- Service d'Hépato-Gastro-Entérologie et Endoscopies Digestives, Hôpital Européen Georges Pompidou, APHP.Centre-Université Paris Cité, Paris, France
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Ntampakis G, Pramateftakis MG, Anestiadou E, Bitsianis S, Ioannidis O, Bekiari C, Koliakos G, Karakota M, Tsakona A, Cheva A, Angelopoulos S. Experimental models of high-risk bowel anastomosis in rats: A systematic review. World J Exp Med 2024; 14:94135. [PMID: 38948424 PMCID: PMC11212746 DOI: 10.5493/wjem.v14.i2.94135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Revised: 04/23/2024] [Accepted: 05/10/2024] [Indexed: 06/19/2024] Open
Abstract
BACKGROUND Anastomotic leaks remain one of the most dreaded complications in gastrointestinal surgery causing significant morbidity, that negatively affect the patients' quality of life. Experimental studies play an important role in understanding the pathophysiological background of anastomotic healing and there are still many fields that require further investigation. Knowledge drawn from these studies can lead to interventions or techniques that can reduce the risk of anastomotic leak in patients with high-risk features. Despite the advances in experimental protocols and techniques, designing a high-quality study is still challenging for the investigators as there is a plethora of different models used. AIM To review current state of the art for experimental protocols in high-risk anastomosis in rats. METHODS This systematic review was performed according to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. To identify eligible studies, a comprehensive literature search was performed in the electronic databases PubMed (MEDLINE) and Scopus, covering the period from conception until 18 October 2023. RESULTS From our search strategy 102 studies were included and were categorized based on the mechanism used to create a high-risk anastomosis. Methods of assessing anastomotic healing were extracted and were individually appraised. CONCLUSION Anastomotic healing studies have evolved over the last decades, but the findings are yet to be translated into human studies. There is a need for high-quality, well-designed studies that will help to the better understanding of the pathophysiology of anastomotic healing and the effects of various interventions.
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Affiliation(s)
- Georgios Ntampakis
- Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece
| | | | - Elissavet Anestiadou
- Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece
| | - Stefanos Bitsianis
- Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece
| | - Orestis Ioannidis
- Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece
| | - Chryssa Bekiari
- Laboratory of Anatomy and Histology, School of Veterinary Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
- Experimental and Research Center, Papageorgiou General Hospital of Thessaloniki, Thessaloniki 56403, Greece
| | - George Koliakos
- Laboratory of Biochemistry, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
| | - Maria Karakota
- Laboratory of Biochemistry, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
| | - Anastasia Tsakona
- Department of Pathology, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
| | - Angeliki Cheva
- Department of Pathology, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
| | - Stamatios Angelopoulos
- Fourth Department of Surgery, Medical School, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece
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Geropoulos G, Psarras K, Papaioannou M, Geropoulos V, Niti A, Nikolaidou C, Koimtzis G, Symeonidis N, Pavlidis ET, Koliakos G, Pavlidis TE, Galanis I. The Effectiveness of Adipose Tissue-Derived Mesenchymal Stem Cells Mixed with Platelet-Rich Plasma in the Healing of Inflammatory Bowel Anastomoses: A Pre-Clinical Study in Rats. J Pers Med 2024; 14:121. [PMID: 38276243 PMCID: PMC10817310 DOI: 10.3390/jpm14010121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Revised: 12/22/2023] [Accepted: 12/25/2023] [Indexed: 01/27/2024] Open
Abstract
Introduction: Multiple factors have been linked with increased risk of anastomotic leak in bowel surgery, including infections, inflammatory bowel disease, patient comorbidities and poor surgical technique. The aim of this study was to investigate the positive effect, if any, of adipose derived mesenchymal stem cells (MSCs) mixed with platelet-rich plasma (PRP) in the healing of bowel anastomoses, in an inflammatory environment after establishment of experimental colitis. Materials and Methods: Thirty-five male Wistar rats were divided into five groups of seven animals: normal controls, colitis controls, PRP, MSCs, and PRP+MSCs. All groups underwent laparotomy, one-cm segmental colectomy and anastomosis in situ. In the colitis group, colectomy was performed at the affected area. Colitis was previously established by transrectal administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) except for the normal controls. Post-mortem histopathological, tissue hydroxyproline and anastomotic bursting pressure (ABP) assessments were performed. The Mann-Whitney U test was used to assess statistical significance differences between groups. Results: No perioperative mortality was noted. Tissue hydroxyproline and ABP were significantly increased in the group of PRP+MSCs compared to colitis controls (p = 0.0151 and p = 0.0104, respectively). Inflammatory cell infiltration was lower and fibroblast activity higher in PRP+MSCs group, but not statistically significant (p > 0.05). Neoangiogenesis (p = 0.0073) and anastomotic area epithelialization (p = 0.0182) were significantly higher in PRP + MSCs group compared to colitis controls. Discussion: The synergistic effect of the PRP and MSCs is apparently responsible for the improved healing markers in bowel anastomoses even on inflammatory bowel. This gives hope for primary anastomoses and stoma saving in many emergency and/or elective circumstances, especially in immunocompromised or malnourished patients, even in cases with inflammation or peritonitis. Clinical studies should follow in order to support the clinical application of PRP+MSCs in gastrointestinal anastomoses.
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Affiliation(s)
- Georgios Geropoulos
- 2nd Propaedeutical Department of Surgery, Hippokration Hospital, School of Medicine, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece (G.K.); (N.S.); (E.T.P.); (T.E.P.); (I.G.)
| | - Kyriakos Psarras
- 2nd Propaedeutical Department of Surgery, Hippokration Hospital, School of Medicine, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece (G.K.); (N.S.); (E.T.P.); (T.E.P.); (I.G.)
| | - Maria Papaioannou
- Laboratory of Biological Chemistry, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece;
| | - Vasileios Geropoulos
- 2nd Propaedeutical Department of Surgery, Hippokration Hospital, School of Medicine, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece (G.K.); (N.S.); (E.T.P.); (T.E.P.); (I.G.)
| | - Argyri Niti
- Biohellenika Biotechnology Company, 55535 Thessaloniki, Greece; (A.N.)
| | - Christina Nikolaidou
- Department of Histopathology, Hippokration Hospital, 54642 Thessaloniki, Greece;
| | - Georgios Koimtzis
- 2nd Propaedeutical Department of Surgery, Hippokration Hospital, School of Medicine, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece (G.K.); (N.S.); (E.T.P.); (T.E.P.); (I.G.)
| | - Nikolaos Symeonidis
- 2nd Propaedeutical Department of Surgery, Hippokration Hospital, School of Medicine, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece (G.K.); (N.S.); (E.T.P.); (T.E.P.); (I.G.)
| | - Efstathios T. Pavlidis
- 2nd Propaedeutical Department of Surgery, Hippokration Hospital, School of Medicine, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece (G.K.); (N.S.); (E.T.P.); (T.E.P.); (I.G.)
| | - Georgios Koliakos
- Biohellenika Biotechnology Company, 55535 Thessaloniki, Greece; (A.N.)
| | - Theodoros E. Pavlidis
- 2nd Propaedeutical Department of Surgery, Hippokration Hospital, School of Medicine, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece (G.K.); (N.S.); (E.T.P.); (T.E.P.); (I.G.)
| | - Ioannis Galanis
- 2nd Propaedeutical Department of Surgery, Hippokration Hospital, School of Medicine, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece (G.K.); (N.S.); (E.T.P.); (T.E.P.); (I.G.)
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Ntampakis G, Pramateftakis MG, Ioannidis O, Bitsianis S, Christidis P, Symeonidis S, Koliakos G, Karakota M, Bekiari C, Tsakona A, Cheva A, Aggelopoulos S. The Role of Adipose Tissue Mesenchymal Stem Cells in Colonic Anastomosis Healing in Inflammatory Bowel Disease: Experimental Study in Rats. J Clin Med 2023; 12:6336. [PMID: 37834980 PMCID: PMC10573964 DOI: 10.3390/jcm12196336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2023] [Revised: 09/28/2023] [Accepted: 09/30/2023] [Indexed: 10/15/2023] Open
Abstract
(1) Background: A surgical operation on an inflamed bowel is, diachronically, a challenge for the surgeon, especially for patients with inflammatory bowel disease. Adipose tissue-derived mesenchymal stromal cells are already in use in clinical settings for their anti-inflammatory properties. The rationale of the current study was to use AdMSCs in high-risk anastomoses to monitor if they attenuate inflammation and prevent anastomotic leak. (2) Methods: a total of 4 groups of rats were subjected to a surgical transection of the large intestine and primary anastomosis. In two groups, DSS 5% was administered for 7 days prior to the procedure, to induce acute intestinal inflammation. After the anastomosis, 5 × 106 autologous AdMSCs or an acellular solution was injected locally. Macroscopic evaluation, bursting pressure, hydroxyproline, and inflammatory cytokine expression were the parameters measured on the 8th post-operative day. (3) Results: Significantly less intra-abdominal complications, higher bursting pressures, and a decrease in pro-inflammatory markers were found in the groups that received AdMSCs. No difference in VEGF expression was observed on the 8th post-operative day. (4) Conclusions: AdMSCs attenuate inflammation in cases of acutely inflamed anastomosis.
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Affiliation(s)
- Georgios Ntampakis
- 4th Department of General Surgery, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (G.N.)
| | | | - Orestis Ioannidis
- 4th Department of General Surgery, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (G.N.)
| | - Stefanos Bitsianis
- 4th Department of General Surgery, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (G.N.)
| | - Panagiotis Christidis
- 4th Department of General Surgery, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (G.N.)
| | - Savvas Symeonidis
- 4th Department of General Surgery, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (G.N.)
| | - Georgios Koliakos
- Laboratory of Biochemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
| | - Maria Karakota
- Laboratory of Biochemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
| | - Chrysanthi Bekiari
- Experimental and Research Center, Papageorgiou General Hospital of Thessaloniki, 56403 Thessaloniki, Greece
- Laboratory of Anatomy and Histology, Veterinary School, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
| | - Anastasia Tsakona
- Pathology Department, Faculty of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
| | - Angeliki Cheva
- Pathology Department, Faculty of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
| | - Stamatios Aggelopoulos
- 4th Department of General Surgery, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (G.N.)
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Yu W, Zhou H, Feng X, Liang X, Wei D, Xia T, Yang B, Yan L, Zhao X, Liu H. Mesenchymal stem cell secretome-loaded fibrin glue improves the healing of intestinal anastomosis. Front Bioeng Biotechnol 2023; 11:1103709. [PMID: 37064233 PMCID: PMC10102583 DOI: 10.3389/fbioe.2023.1103709] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2022] [Accepted: 03/24/2023] [Indexed: 04/03/2023] Open
Abstract
Anastomotic leakage is a serious complication following gastrointestinal surgery and one of the leading causes of patient mortality. Despite the significant clinical and economic burden, there are currently no reliable treatment options to improve the healing of intestinal anastomosis and subsequently prevent anastomotic leakage. Recently, the development of regenerative medicine has shown promise for improving anastomotic healing. Recent studies have illustrated that stem cell-derived secretome can enhance tissue regeneration without the safety and ethical limitations of stem cell transplantation. Herein, we developed a fibrin glue topical delivery system loaded with mesenchymal stem cells (MSCs)-derived secretome for controlled delivery of bioactive factors, and evaluated its application potential in improving the healing of intestinal anastomosis. Under in vitro conditions, the MSCs secretome significantly promoted cell proliferation viability in a dose-dependent manner and resulted in the controlled release of growth factors via fibrin glue delivery. We established a rat surgical anastomotic model and experimentally found that MSCs secretome-loaded fibrin glue enhanced anastomotic bursting pressure, increased granulation tissue formation and collagen deposition, and significantly promoted anastomotic healing. Mechanistically, fibrin glue accelerated cell proliferation, angiogenesis, and macrophage M2 polarization at the surgical anastomotic site by releasing bioactive factors in the secretome, and it also alleviated the inflammatory response and cell apoptosis at the anastomotic site. Our results demonstrated for the first time that MSCs-derived secretome could promote the healing of intestinal anastomosis. Considering the accessibility and safety of the cell-free secretome, we believed that secretome-loaded fibrin glue would be a cell-free therapy to accelerate the healing of intestinal anastomosis with great potential for clinical translation.
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Affiliation(s)
- Wenwen Yu
- The Second Clinical Medical College, Lanzhou University, Lanzhou, China
| | - Haicun Zhou
- Department of Breast Surgery, Gansu Maternal and Child Healthcare Hospital, Lanzhou, China
| | - Xueliang Feng
- The Second Clinical Medical College, Lanzhou University, Lanzhou, China
| | - Xiaoqin Liang
- The Second Clinical Medical College, Lanzhou University, Lanzhou, China
| | - Dengwen Wei
- Department of Abdominal Surgery, Gansu Provincial Cancer Hospital, Gansu Provincial Academic Institute for Medical Research, Lanzhou, China
| | - Tianhong Xia
- Key Laboratory of Stem Cells and Gene Drugs of Gansu Province, The 940th Hospital of Joint Logistics Support Force of Chinese People’s Liberation Army, Lanzhou, China
| | - Bin Yang
- Key Laboratory of Stem Cells and Gene Drugs of Gansu Province, The 940th Hospital of Joint Logistics Support Force of Chinese People’s Liberation Army, Lanzhou, China
| | - Long Yan
- Key Laboratory of Stem Cells and Gene Drugs of Gansu Province, The 940th Hospital of Joint Logistics Support Force of Chinese People’s Liberation Army, Lanzhou, China
| | - Xiaochen Zhao
- Key Laboratory of Stem Cells and Gene Drugs of Gansu Province, The 940th Hospital of Joint Logistics Support Force of Chinese People’s Liberation Army, Lanzhou, China
| | - Hongbin Liu
- The Second Clinical Medical College, Lanzhou University, Lanzhou, China
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Carmichael SP, Shin J, Vaughan JW, Chandra PK, Holcomb JB, Atala AJ. Regenerative Medicine Therapies for Prevention of Abdominal Adhesions: A Scoping Review. J Surg Res 2022; 275:252-264. [PMID: 35306261 PMCID: PMC9038705 DOI: 10.1016/j.jss.2022.02.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 12/26/2021] [Accepted: 02/08/2022] [Indexed: 01/02/2023]
Abstract
INTRODUCTION Globally, abdominal adhesions constitute a significant burden of morbidity and mortality. They represent the commonest complication of abdominal operations with a lifelong risk of multiple pathologies, including adhesive small bowel obstruction, female infertility, and chronic pain. Adhesions represent a problem of the entire abdomen, forming at the time of injury and progressing through multiple complex pathways. Clinically available preventative strategies are limited to barrier technologies. Significant knowledge gaps persist in the characterization and mitigation of the involved molecular pathways underlying adhesion formation. Thus, the objectives of this scoping review are to describe the known molecular pathophysiology implicated in abdominal adhesion formation and summarize novel preclinical regenerative medicine preventative strategies for potential future clinical investigation. METHODS A literature review was performed in accordance with the Preferred Reporting Items for Systematic Reviews Extension for Scoping Reviews. Included peer-reviewed publications were published within the last 5 y and contained in vivo preclinical experimental studies of postoperative adhesions with the assessment of underlying mechanisms of adhesion formation and successful therapy for adhesion prevention. Studies not involving regenerative medicine strategies were excluded. Data were qualitatively synthesized. RESULTS A total of 1762 articles were identified. Of these, 1001 records were excluded by the described screening criteria. Sixty-eight full-text articles were evaluated for eligibility, and 11 studies were included for review. CONCLUSIONS Novel and reliable preventative strategies are urgently needed. Recent experimental data propose novel regenerative medicine targets for adhesion prevention.
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Affiliation(s)
- Samuel P Carmichael
- Division of Acute Care Surgery, Department of Surgery, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina; Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.
| | - Jaewook Shin
- Department of Surgery, Warren Alpert Medical School of Brown University, Providence, Rhode Island
| | - John W Vaughan
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina
| | - Prafulla K Chandra
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina
| | - John B Holcomb
- Department of Surgery, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama
| | - Anthony J Atala
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina
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Trébol J, Georgiev-Hristov T, Pascual-Miguelañez I, Guadalajara H, García-Arranz M, García-Olmo D. Stem cell therapy applied for digestive anastomosis: Current state and future perspectives. World J Stem Cells 2022; 14:117-141. [PMID: 35126832 PMCID: PMC8788180 DOI: 10.4252/wjsc.v14.i1.117] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 06/21/2021] [Accepted: 12/31/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Digestive tract resections are usually followed by an anastomosis. Anastomotic leakage, normally due to failed healing, is the most feared complication in digestive surgery because it is associated with high morbidity and mortality. Despite technical and technological advances and focused research, its rates have remained almost unchanged the last decades. In the last two decades, stem cells (SCs) have been shown to enhance healing in animal and human studies; hence, SCs have emerged since 2008 as an alternative to improve anastomoses outcomes.
AIM To summarise the published knowledge of SC utilisation as a preventative tool for hollow digestive viscera anastomotic or suture leaks.
METHODS PubMed, Science Direct, Scopus and Cochrane searches were performed using the key words “anastomosis”, “colorectal/colonic anastomoses”, “anastomotic leak”, “stem cells”, “progenitor cells”, “cellular therapy” and “cell therapy” in order to identify relevant articles published in English and Spanish during the years of 2000 to 2021. Studies employing SCs, performing digestive anastomoses in hollow viscera or digestive perforation sutures and monitoring healing were finally included. Reference lists from the selected articles were reviewed to identify additional pertinent articles.
Given the great variability in the study designs, anastomotic models, interventions (SCs, doses and vehicles) and outcome measures, performing a reliable meta-analysis was considered impossible, so we present the studies, their results and limitations.
RESULTS Eighteen preclinical studies and three review papers were identified; no clinical studies have been published and there are no registered clinical trials. Experimental studies, mainly in rat and porcine models and occasionally in very adverse conditions such as ischaemia or colitis, have been demonstrated SCs as safe and have shown some encouraging morphological, functional and even clinical results. Mesenchymal SCs are mostly employed, and delivery routes are mainly local injections and cell sheets followed by biosutures (sutures coated by SCs) or purely topical. As potential weaknesses, animal models need to be improved to make them more comparable and equivalent to clinical practice, and the SC isolation processes need to be standardised. There is notable heterogeneity in the studies, making them difficult to compare. Further investigations are needed to establish the indications, the administration system, potential adjuvants, the final efficacy and to confirm safety and exclude definitively oncological concerns.
CONCLUSION The future role of SC therapy to induce healing processes in digestive anastomoses/sutures still needs to be determined and seems to be currently far from clinical use.
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Affiliation(s)
- Jacobo Trébol
- Servicio de Cirugía General y del Aparato Digestivo, Complejo Asistencial Universitario de Salamanca, Salamanca 37007, Spain
- Departamento de Anatomía e Histología Humanas, Universidad de Salamanca, Salamanca 37007, Spain
| | - Tihomir Georgiev-Hristov
- Servicio de Cirugía General y del Aparato Digestivo, Hospital General Universitario de Villalba, Madrid 28400, Spain
| | - Isabel Pascual-Miguelañez
- Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitario La Paz, Madrid 28046, Spain
| | - Hector Guadalajara
- Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitario Fundación Jiménez Díaz, Madrid 28040, Spain
| | - Mariano García-Arranz
- Grupo de Investigación en Nuevas Terapias, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz, Madrid 28040, Spain
- Departamento de Cirugía, Universidad Autónoma de Madrid, Madrid 28029, Spain
| | - Damian García-Olmo
- Departamento de Cirugía, Universidad Autónoma de Madrid, Madrid 28029, Spain
- Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitario Fundación Jiménez Díaz y Grupo Quiron-Salud Madrid, Madrid 28040, Spain
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Effects of Neoadjuvant Radiotherapy on Postoperative Complications in Rectal Cancer: A Meta-Analysis. JOURNAL OF ONCOLOGY 2022; 2022:8197701. [PMID: 35035483 PMCID: PMC8754670 DOI: 10.1155/2022/8197701] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 11/29/2021] [Accepted: 12/18/2021] [Indexed: 02/06/2023]
Abstract
Objective Neoadjuvant radiotherapy (nRT) is an important treatment approach for rectal cancer. The relationship, however, between nRT and postoperative complications is still controversial. Here, we conducted a meta-analysis to evaluate such concerns. Methods The electronic literature from 1983 to 2021 was searched in PubMed, Embase, and Web of Science. Postoperative complications after nRT were included in the meta-analysis. The pooled odds ratio (OR) was calculated by the random-effects model. Statistical analysis was conducted by Review Manager 5.3 and STATA 14. Results A total of 23,723 patients from 49 studies were included in the meta-analysis. The pooled results showed that nRT increased the risk of anastomotic leakage (AL) compared to upfront surgery (OR = 1.23; 95% CI, 1.07-1.41; p=0.004). Subgroup analysis suggested that both long-course (OR = 1.20, 95% CI 1.03-1.40; p=0.02) and short-course radiotherapy (OR = 1.25, 95% CI, 1.02-1.53; p=0.04) increased the incidence of AL. In addition, nRT was the main risk factor for wound infection and pelvic abscess. The pooled data in randomized controlled trials, however, indicated that nRT was not associated with AL (OR = 1.01; 95% CI 0.82-1.26; p=0.91). Conclusions nRT may increase the risk of AL, wound infection, and pelvic abscess compared to upfront surgery among patients with rectal cancer.
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Burke JR, Helliwell J, Wong J, Quyn A, Herrick S, Jayne D. The use of mesenchymal stem cells in animal models for gastrointestinal anastomotic leak: A systematic review. Colorectal Dis 2021; 23:3123-3140. [PMID: 34363723 DOI: 10.1111/codi.15864] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 07/29/2021] [Accepted: 07/29/2021] [Indexed: 02/08/2023]
Abstract
AIM Anastomotic leak is the most feared complication of gastrointestinal surgery. Mesenchymal stem cell technology is used clinically to promote wound healing; however, the safety and efficacy of this technology on anastomotic healing has yet to be defined. The aim of this study was to investigate whether mesenchymal stem cells confer any benefit when applied to animal models for gastrointestinal anastomotic leak, identify the methodology and how efficacy is assessed. METHODS The MEDLINE, EMBASE, WebofScience and Cochrane Library databases were interrogated between 1 January1947 to 1 May 2020. All studies where mesenchymal stem cells were applied to laboratory animal leak models to demonstrate a healing effect were considered. All experimental and histological outcomes were examined. Compliance to ARRIVE and current International Consensus was assessed. RESULTS A total of 1205 studies were screened. Twelve studies reported on 438 gastrointestinal anastomoses in four species using 11 models; seven in the colon. No studies utilised a model with a known leak rate. Significant variance was observed in histological outcomes with efficacy demonstrated in five out of 12 studies. One study demonstrated a benefit in leak rate. Colorectal studies had a greater median ARRIVE compliance, 60.8% (IQR 63.2-64.5) compared to noncolorectal 45.4% (IQR 43.8-49.0). CONCLUSIONS Mesenchymal stem cell delivery to an animal anastomosis is safe and feasible. Use may confer benefit but findings are currently limited to surrogate histological outcomes. There is consistency in outcome measures reported but variance in how this is assessed. Poor compliance to ARRIVE but good compliance to current international consensus in leak models of the colon was observed.
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Affiliation(s)
- Joshua Richard Burke
- The John Goligher Colorectal Surgery Unit, St. James's University Hospital, Leeds Teaching Hospital Trust, Leeds, UK
| | - Jack Helliwell
- The John Goligher Colorectal Surgery Unit, St. James's University Hospital, Leeds Teaching Hospital Trust, Leeds, UK
| | - Jason Wong
- Division of Cell Matrix Biology & Regenerative Medicine, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK
| | - Aaron Quyn
- The John Goligher Colorectal Surgery Unit, St. James's University Hospital, Leeds Teaching Hospital Trust, Leeds, UK
| | - Sarah Herrick
- Division of Cell Matrix Biology & Regenerative Medicine, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK
| | - David Jayne
- The John Goligher Colorectal Surgery Unit, St. James's University Hospital, Leeds Teaching Hospital Trust, Leeds, UK
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10
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Gundestrup AK, Lynggaard CD, Forner L, Heino TJ, Jakobsen KK, Fischer-Nielsen A, Grønhøj C, von Buchwald C. Mesenchymal Stem Cell Therapy for Osteoradionecrosis of the Mandible: a Systematic Review of Preclinical and Human Studies. Stem Cell Rev Rep 2021; 16:1208-1221. [PMID: 32869179 DOI: 10.1007/s12015-020-10034-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Osteoradionecrosis (ORN) of the mandible is a severe complication of radiotherapy for head and neck cancer and is arduously difficult to manage. Current treatment options carry risks with some patients remaining incurable. Mesenchymal stromal/stem cell (MSC) therapy has shown promising results supporting osteogenesis and regeneration of radiotherapy-damaged tissues. The aim of this study was to systematically review the literature on the safety and efficacy of MSCs in treating ORN. METHODS A systematic search was performed on MEDLINE, Embase, Cochranes Library online databases, and clinicaltrials.gov to identify preclinical and clinical studies examining the effect of MSCs on osseous healing of ORN. The preclinical studies were assessed according to the SYRCLEs guidelines and risk of bias tool. RESULTS Six studies (n = 142) from 5 countries were eligible for analysis. Of these four were preclinical studies and two clinical case studies. Preclinical studies found MSC treatment to be safe, demonstrating bone restorative effects and improved soft tissue regeneration. In the clinical cases, healing of bone and soft tissue was reported with no serious adverse events. CONCLUSION The evidence from the included studies suggests that MSCs may have beneficial regenerative effects on the healing of ORN. None of the studies reported adverse events with the use of MSCs. More carefully controlled studies with well-identified cells are however needed to demonstrate the efficacy of MSCs in a clinical setting. Graphical abstract.
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Affiliation(s)
- Anders Kierkegaard Gundestrup
- Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Charlotte Duch Lynggaard
- Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Lone Forner
- Department of Oral and Maxillofacial Surgery, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Terhi J Heino
- Institute of Biomedicine, Faculty of Medicine, University of Turku, Turku, Finland
| | - Kathrine Kronberg Jakobsen
- Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Anne Fischer-Nielsen
- Department of Immunology, Cell Therapy Facility, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Christian Grønhøj
- Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Christian von Buchwald
- Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
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Moussa L, Lapière A, Squiban C, Demarquay C, Milliat F, Mathieu N. BMP Antagonists Secreted by Mesenchymal Stromal Cells Improve Colonic Organoid Formation: Application for the Treatment of Radiation-induced Injury. Cell Transplant 2021; 29:963689720929683. [PMID: 33108903 PMCID: PMC7784604 DOI: 10.1177/0963689720929683] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Radiation therapy is crucial in the therapeutic arsenal to cure cancers; however, non-neoplastic tissues around an abdominopelvic tumor can be damaged by ionizing radiation. In particular, the radio-induced death of highly proliferative stem/progenitor cells of the colonic mucosa could induce severe ulcers. The importance of sequelae for patients with gastrointestinal complications after radiotherapy and the absence of satisfactory management has opened the field to the testing of innovative treatments. The aim of this study was to use adult epithelial cells from the colon, to reduce colonic injuries in an animal model reproducing radiation damage observed in patients. We demonstrated that transplanted in vitro-amplified epithelial cells from colonic organoids (ECO) of C57/Bl6 mice expressing green fluorescent protein implant, proliferate, and differentiate in irradiated mucosa and reduce ulcer size. To improve the therapeutic benefit of ECO-based treatment with clinical translatability, we performed co-injection of ECO with mesenchymal stromal cells (MSCs), cells involved in niche function and widely used in clinical trials. We observed in vivo an improvement of the therapeutic benefit and in vitro analysis highlighted that co-culture of MSCs with ECO increases the number, proliferation, and size of colonic organoids. We also demonstrated, using gene expression analysis and siRNA inhibition, the involvement of bone morphogenetic protein antagonists in MSC-induced organoid formation. This study provides evidence of the potential of ECO to limit late radiation effects on the colon and opens perspectives on combined strategies to improve their amplification abilities and therapeutic effects.
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Affiliation(s)
- Lara Moussa
- Human Health Department, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PSE-SANTE, SERAMED, LRMed, Fontenay-aux-Roses, France
| | - Alexia Lapière
- Human Health Department, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PSE-SANTE, SERAMED, LRMed, Fontenay-aux-Roses, France
| | - Claire Squiban
- Human Health Department, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PSE-SANTE, SERAMED, LRMed, Fontenay-aux-Roses, France
| | - Christelle Demarquay
- Human Health Department, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PSE-SANTE, SERAMED, LRMed, Fontenay-aux-Roses, France
| | - Fabien Milliat
- Human Health Department, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PSE-SANTE, SERAMED, LRMed, Fontenay-aux-Roses, France
| | - Noëlle Mathieu
- Human Health Department, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PSE-SANTE, SERAMED, LRMed, Fontenay-aux-Roses, France
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12
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The impact of gastrointestinal anastomotic leaks on survival of patients undergoing cytoreductive surgery and heated intraperitoneal chemotherapy. Am J Surg 2021; 223:331-338. [PMID: 33832737 DOI: 10.1016/j.amjsurg.2021.03.061] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Revised: 02/15/2021] [Accepted: 03/28/2021] [Indexed: 12/29/2022]
Abstract
BACKGROUND Gastrointestinal (GI) leaks after cytoreductive surgery and hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC) is a known life-threatening complication that may alter patients' outcomes. Our aim is to investigate risk factors associated with GI leaks and evaluate the impact of GI leaks on patient's oncological outcomes. METHODS A retrospective analysis of perioperative and oncological outcomes of patients with and without GI leaks after CRS/HIPEC. RESULTS Out of 191 patients included in this study, GI leaks were identified in 17.8% (34/191) of patients. Small bowel anastomoses were the most common site (44%). Most of the GI leaks were managed conservatively and re-operation was needed in 44.1% of cases. Univariate analysis identified higher PCI (p = 0.03), higher number of packed cells transfused (p = 0.036), pelvic peritonectomy (p = 0.013), high number of anastomoses (p = 0.003) and colonic resection (p = 0.042) as factors associated with GI leaks. Multivariate analysis identified stapled anastomoses (OR 2.59, p = 0.001) and pelvic peritonectomy (OR 2.33, p = 0.044) as independent factors associated with GI leaks. Disease-free survival tended to be worse in the leak group but did not reach statistical significance (p = 0.235). The 3- and 5-year OS was 73.2% and 52.9% in the leak group compared to 75.8% and 73.2% in the non-leak group (p = 0.236). CONCLUSIONS GI leak showed no impact on overall and disease free survival after CRS/HIPEC.Avoidance of stapled reconstruction in high risk patients with high tumor burden and large number of anastomoses may yield improved outcomes.
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Therapeutic Potential of Mesenchymal Stromal Cells and Extracellular Vesicles in the Treatment of Radiation Lesions-A Review. Cells 2021; 10:cells10020427. [PMID: 33670501 PMCID: PMC7922519 DOI: 10.3390/cells10020427] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Revised: 02/08/2021] [Accepted: 02/13/2021] [Indexed: 12/14/2022] Open
Abstract
Ionising radiation-induced normal tissue damage is a major concern in clinic and public health. It is the most limiting factor in radiotherapy treatment of malignant diseases. It can also cause a serious harm to populations exposed to accidental radiation exposure or nuclear warfare. With regard to the clinical use of radiation, there has been a number of modalities used in the field of radiotherapy. These includes physical modalities such modified collimators or fractionation schedules in radiotherapy. In addition, there are a number of pharmacological agents such as essential fatty acids, vasoactive drugs, enzyme inhibitors, antioxidants, and growth factors for the prevention or treatment of radiation lesions in general. However, at present, there is no standard procedure for the treatment of radiation-induced normal tissue lesions. Stem cells and their role in tissue regeneration have been known to biologists, in particular to radiobiologists, for many years. It was only recently that the potential of stem cells was studied in the treatment of radiation lesions. Stem cells, immediately after their successful isolation from a variety of animal and human tissues, demonstrated their likely application in the treatment of various diseases. This paper describes the types and origin of stem cells, their characteristics, current research, and reviews their potential in the treatment and regeneration of radiation induced normal tissue lesions. Adult stem cells, among those mesenchymal stem cells (MSCs), are the most extensively studied of stem cells. This review focuses on the effects of MSCs in the treatment of radiation lesions.
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14
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Helissey C, Cavallero S, Brossard C, Dusaud M, Chargari C, François S. Chronic Inflammation and Radiation-Induced Cystitis: Molecular Background and Therapeutic Perspectives. Cells 2020; 10:E21. [PMID: 33374374 PMCID: PMC7823735 DOI: 10.3390/cells10010021] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Revised: 12/10/2020] [Accepted: 12/22/2020] [Indexed: 12/14/2022] Open
Abstract
Radiation cystitis is a potential complication following the therapeutic irradiation of pelvic cancers. Its clinical management remains unclear, and few preclinical data are available on its underlying pathophysiology. The therapeutic strategy is difficult to establish because few prospective and randomized trials are available. In this review, we report on the clinical presentation and pathophysiology of radiation cystitis. Then we discuss potential therapeutic approaches, with a focus on the immunopathological processes underlying the onset of radiation cystitis, including the fibrotic process. Potential therapeutic avenues for therapeutic modulation will be highlighted, with a focus on the interaction between mesenchymal stromal cells and macrophages for the prevention and treatment of radiation cystitis.
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Affiliation(s)
- Carole Helissey
- Department of Radiation Biological Effects, French Armed Forces Biomedical Research Institute, 91220 Brétigny-sur-Orge, France; (C.H.); (S.C.); (C.C.)
- Clinical Unit Research, HIA Bégin, 94160 Saint-Mandé, France
| | - Sophie Cavallero
- Department of Radiation Biological Effects, French Armed Forces Biomedical Research Institute, 91220 Brétigny-sur-Orge, France; (C.H.); (S.C.); (C.C.)
| | - Clément Brossard
- Radiobiology of Medical Exposure Laboratory (LRMed), Institute for Radiological Protection and Nuclear Safety (IRSN), 92260 Fontenay-aux-Roses, France;
| | - Marie Dusaud
- Department of Urology, HIA Bégin, 94160 Saint-Mand, France;
| | - Cyrus Chargari
- Department of Radiation Biological Effects, French Armed Forces Biomedical Research Institute, 91220 Brétigny-sur-Orge, France; (C.H.); (S.C.); (C.C.)
- Gustave Roussy Comprehensive Cancer Center, Department of Radiation Oncology, 94805 Villejuif, France
- French Military Health Academy, Ecole du Val-de-Grâce (EVDG), 75005 Paris, France
| | - Sabine François
- Department of Radiation Biological Effects, French Armed Forces Biomedical Research Institute, 91220 Brétigny-sur-Orge, France; (C.H.); (S.C.); (C.C.)
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15
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Fang AH, Chao W, Ecker M. Review of Colonic Anastomotic Leakage and Prevention Methods. J Clin Med 2020; 9:E4061. [PMID: 33339209 PMCID: PMC7765607 DOI: 10.3390/jcm9124061] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Revised: 12/10/2020] [Accepted: 12/12/2020] [Indexed: 12/15/2022] Open
Abstract
Although surgeries involving anastomosis are relatively common, anastomotic leakages are potentially deadly complications of colorectal surgeries due to increased risk of morbidity and mortality. As a result of the potentially fatal effects of anastomotic leakages, a myriad of techniques and treatments have been developed to treat these unfortunate cases. In order to better understand the steps taken to treat this complication, we have created a composite review involving some of the current and best treatments for colonic anastomotic leakage that are available. The aim of this article is to present a background review of colonic anastomotic leakage, as well as current strategies to prevent and treat this condition, for a broader audience, including scientist, engineers, and especially biomedical engineers.
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Affiliation(s)
- Alex H. Fang
- Texas Academy of Mathematics and Science, University of North Texas, Denton, TX 76203, USA; (A.H.F.); (W.C.)
- Department of Biomedical Engineering, University of North Texas, Denton, TX 76203, USA
| | - Wilson Chao
- Texas Academy of Mathematics and Science, University of North Texas, Denton, TX 76203, USA; (A.H.F.); (W.C.)
- Department of Biomedical Engineering, University of North Texas, Denton, TX 76203, USA
| | - Melanie Ecker
- Department of Biomedical Engineering, University of North Texas, Denton, TX 76203, USA
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16
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Effect of Breast Cancer and Adjuvant Therapy on Adipose-Derived Stromal Cells: Implications for the Role of ADSCs in Regenerative Strategies for Breast Reconstruction. Stem Cell Rev Rep 2020; 17:523-538. [PMID: 32929604 DOI: 10.1007/s12015-020-10038-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/04/2020] [Indexed: 12/14/2022]
Abstract
Tissue engineering using Adipose Derived Stromal Cells (ADSCs) has emerged as a novel regenerative medicine approach to replace and reconstruct soft tissue damaged or lost as a result of disease process or therapeutic surgical resection. ADSCs are an attractive cell source for soft tissue regeneration due to the fact that they are easily accessible, multipotent, non-immunogenic and pro-angiogenic. ADSC based regenerative strategies have been successfully translated to the clinical setting for the treatment of Crohn's fistulae, musculoskeletal pathologies, wound healing, and cosmetic breast augmentation (fat grafting). ADSCs are particularly attractive as a source for adipose tissue engineering as they exhibit preferential differentiation to adipocytes and support maintenance of mature adipose graft volume. The potential for reconstruction with an autologous tissue sources and a natural appearance and texture is particularly appealing in the setting of breast cancer; up to 40% of patients require mastectomy for locoregional control and current approaches to post-mastectomy breast reconstruction (PMBR) are limited by the potential for complications at the donor and reconstruction sites. Despite their potential, the use of ADSCs in breast cancer patients is controversial due to concerns regarding oncological safety. These concerns relate to the regeneration of tissue at a site where a malignancy has been treated and the impact this may have on stimulating local disease recurrence or dissemination. Pre-clinical data suggest that ADSCs exhibit pro-oncogenic characteristics and are involved in stimulating progression, and growth of tumour cells. However, there have been conflicting reports on the oncologic outcome, in terms of locoregional recurrence, for breast cancer patients in whom ADSC enhanced fat grafting was utilised as an alternative to reconstruction for small volume defects. A further consideration which may impact the successful translation of ADSC based regenerative strategies for post cancer reconstruction is the potential effects of cancer therapy. This review aims to address the effect of malignant cells, adjuvant therapies and patient-specific factors that may influence the success of regenerative strategies using ADSCs for post cancer tissue regeneration.
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Tovar I, Guerrero R, López-Peñalver JJ, Expósito J, Ruiz de Almodóvar JM. Rationale for the Use of Radiation-Activated Mesenchymal Stromal/Stem Cells in Acute Respiratory Distress Syndrome. Cells 2020; 9:cells9092015. [PMID: 32887260 PMCID: PMC7565018 DOI: 10.3390/cells9092015] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Revised: 08/29/2020] [Accepted: 08/31/2020] [Indexed: 12/17/2022] Open
Abstract
We have previously shown that the combination of radiotherapy with human umbilical-cord-derived mesenchymal stromal/stem cells (MSCs) cell therapy significantly reduces the size of the xenotumors in mice, both in the directly irradiated tumor and in the distant nonirradiated tumor or its metastasis. We have also shown that exosomes secreted from MSCs preirradiated with 2 Gy are quantitatively, functionally and qualitatively different from the exosomes secreted from nonirradiated mesenchymal cells, and also that proteins, exosomes and microvesicles secreted by MSCs suffer a significant change when the cells are activated or nonactivated, with the amount of protein present in the exosomes of the preirradiated cells being 1.5 times greater compared to those from nonirradiated cells. This finding correlates with a dramatic increase in the antitumor activity of the radiotherapy when is combined with MSCs or with preirradiated mesenchymal stromal/stem cells (MSCs*). After the proteomic analysis of the load of the exosomes released from both irradiated and nonirradiated cells, we conclude that annexin A1 is the most important and significant difference between the exosomes released by the cells in either status. Knowing the role of annexin A1 in the control of hypoxia and inflammation that is characteristic of acute respiratory-distress syndrome (ARDS), we designed a hypothetical therapeutic strategy, based on the transplantation of mesenchymal stromal/stem cells stimulated with radiation, to alleviate the symptoms of patients who, due to pneumonia caused by SARS-CoV-2, require to be admitted to an intensive care unit for patients with life-threatening conditions. With this hypothesis, we seek to improve the patients' respiratory capacity and increase the expectations of their cure.
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Affiliation(s)
- Isabel Tovar
- Departamento de Oncología Médica y Radioterapia, Servicio Andaluz de Salud (SAS), Avenida de las Fuerzas Armadas 2, 18014 Granada, Spain; (I.T.); (R.G.); (J.E.)
- Instituto de Investigación Biosanitaria, Ibis Granada, Hospital Universitario Virgen de las Nieves, Avenida de las Fuerzas Armadas 2, 18014 Granada, Spain
| | - Rosa Guerrero
- Departamento de Oncología Médica y Radioterapia, Servicio Andaluz de Salud (SAS), Avenida de las Fuerzas Armadas 2, 18014 Granada, Spain; (I.T.); (R.G.); (J.E.)
- Instituto de Investigación Biosanitaria, Ibis Granada, Hospital Universitario Virgen de las Nieves, Avenida de las Fuerzas Armadas 2, 18014 Granada, Spain
| | - Jesús J. López-Peñalver
- Unidad de Radiología Experimental, Centro de Investigación Biomédica, Universidad de Granada, PTS Granada, 18016 Granada, Spain;
| | - José Expósito
- Departamento de Oncología Médica y Radioterapia, Servicio Andaluz de Salud (SAS), Avenida de las Fuerzas Armadas 2, 18014 Granada, Spain; (I.T.); (R.G.); (J.E.)
- Instituto de Investigación Biosanitaria, Ibis Granada, Hospital Universitario Virgen de las Nieves, Avenida de las Fuerzas Armadas 2, 18014 Granada, Spain
- Departamento de Radiología y Medicina Física, Facultad de Medicina, Universidad de Granada, PTS Granada, 18016 Granada, Spain
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Reischl S, Wilhelm D, Friess H, Neumann PA. Innovative approaches for induction of gastrointestinal anastomotic healing: an update on experimental and clinical aspects. Langenbecks Arch Surg 2020; 406:971-980. [PMID: 32803330 PMCID: PMC8208906 DOI: 10.1007/s00423-020-01957-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Accepted: 08/04/2020] [Indexed: 12/17/2022]
Abstract
PURPOSE In most cases, traditional techniques to perform an anastomosis following gastrointestinal resections lead to successful healing. However, despite focused research in the field, in certain high-risk situations leakage rates remain almost unchanged. Here, additional techniques may help the surgeon to protect the anastomosis and prevent leakage. We give an overview of some of the latest developments on experimental and clinical techniques for induction of anastomotic healing. METHODS We performed a review of the current literature on approaches to improve anastomotic healing. RESULTS Many promising approaches with a high clinical potential are in the developmental pipeline. Highly experimental approaches like inhibition of matrix metalloproteinases, stem cell therapy, hyperbaric oxygen therapy, induction of the hypoxic adaptive response, and the administration of growth factors are still in the preclinical phase. Other more clinical developments aim to strengthen the anastomotic suture line mechanically while shielding it from the influence of the microbiome. Among them are gluing, seaming the staple line, attachment of laminar biomaterials, and temporary intraluminal tubes. In addition, individualized bowel preparation, selectively reducing certain detrimental microbial populations could become the next stage of bowel preparation. Compression anastomoses are evolving as an equivalent technique additional to established hand-sewn and stapled anastomoses. Fluorescence angiography and flexible endoscopy could complement intraoperative quality control additionally to the air leak tests. Virtual ileostomy is a concept to prepare the bowel for the easy formation of a stoma in case of leakage. CONCLUSION A variety of promising diagnostic and prophylactic measures that may support the surgeon in identifying high-risk anastomoses and support them according to their potential deficits is currently in development.
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Affiliation(s)
- Stefan Reischl
- Department of Surgery, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - Dirk Wilhelm
- Department of Surgery, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - Helmut Friess
- Department of Surgery, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - Philipp-Alexander Neumann
- Department of Surgery, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
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Chen C, Zhang Q, Yu W, Chang B, Le AD. Oral Mucositis: An Update on Innate Immunity and New Interventional Targets. J Dent Res 2020; 99:1122-1130. [PMID: 32479139 DOI: 10.1177/0022034520925421] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Oral mucositis (OM), a common debilitating toxicity associated with chemo- and radiation therapies, is a significant unmet clinical need for head and neck cancer patients. The biological complexities of chemoradiotherapy-induced OM involve interactions among disrupted tissue structures, inflammatory infiltrations, and oral microbiome, whereby several master inflammatory pathways constitute the complicated regulatory networks. Oral mucosal damages triggered by chemoradiotherapy-induced cell apoptosis were further exacerbated by the amplified inflammatory cascades dominantly governed by the innate immune responses. The coexistence of microbiome and innate immune components in oral mucosal barriers indicates that a signaling hub coordinates the interaction between environmental cues and host cells during tissue and immune homeostasis. Dysbiotic shifts in oral microbiota caused by cytotoxic cancer therapies may also contribute to the progression and severity of chemoradiotherapy-induced OM. In this review, we have updated the mechanisms involving innate immunity-governed inflammatory cascades in the pathobiology of chemoradiotherapy-induced OM and the development of new interventional targets for the management of this severe morbidity in head and neck cancer patients.
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Affiliation(s)
- C Chen
- Department of Oral & Maxillofacial Surgery & Pharmacology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.,Center of Innovation & Precision Dentistry, School of Dental Medicine, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA, USA
| | - Q Zhang
- Department of Oral & Maxillofacial Surgery & Pharmacology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - W Yu
- Department of Orthodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - B Chang
- Department of Oral & Maxillofacial Surgery & Pharmacology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.,Department of Oral & Maxillofacial Surgery, Penn Medicine Hospital of the University of Pennsylvania, Philadelphia, PA, USA
| | - A D Le
- Department of Oral & Maxillofacial Surgery & Pharmacology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.,Center of Innovation & Precision Dentistry, School of Dental Medicine, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA, USA.,Department of Oral & Maxillofacial Surgery, Penn Medicine Hospital of the University of Pennsylvania, Philadelphia, PA, USA
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Farias VDA, Tovar I, del Moral R, O'Valle F, Expósito J, Oliver FJ, Ruiz de Almodóvar JM. Enhancing the Bystander and Abscopal Effects to Improve Radiotherapy Outcomes. Front Oncol 2020; 9:1381. [PMID: 31970082 PMCID: PMC6960107 DOI: 10.3389/fonc.2019.01381] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2019] [Accepted: 11/22/2019] [Indexed: 12/12/2022] Open
Abstract
In this paper, we summarize published articles and experiences related to the attempt to improve radiotherapy outcomes and, thus, to personalize the radiation treatment according to the individual characteristics of each patient. The evolution of ideas and the study of successively published data have led us to envisage new biophysical models for the interpretation of tumor and healthy normal tissue response to radiation. In the development of the model, we have shown that when mesenchymal stem cells (MSCs) and radiotherapy are administered simultaneously in experimental radiotherapy on xenotumors implanted in a murine model, the results of the treatment show the existence of a synergic mechanism that is able to enhance the local and systemic actions of the radiation both on the treated tumor and on its possible metastasis. We are convinced that, due to the physical hallmarks that characterize the neoplastic tissues, the physical-chemical tropism of MSCs, and the widespread functions of macromolecules, proteins, and exosomes released from activated MSCs, the combination of radiotherapy plus MSCs used intratumorally has the effect of counteracting the pro-tumorigenic and pro-metastatic signals that contribute to the growth, spread, and resistance of the tumor cells. Therefore, we have concluded that MSCs are appropriate for therapeutic use in a clinical trial for rectal cancer combined with radiotherapy, which we are going to start in the near future.
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Affiliation(s)
- Virgínea de Araújo Farias
- Centro de Investigación Biomédica, Instituto Universitario de Investigación en Biopatología y Medicina Regenerativa, PTS Granada, Granada, Spain
- CIBERONC (Instituto de Salud Carlos III), Granada, Spain
- Instituto de Parasitología y Biomedicina “López Neyra”, Consejo Superior de Investigaciones Científicas, PTS Granada, Granada, Spain
| | - Isabel Tovar
- Complejo Hospitalario de Granada, Servicio Andaluz de Salud, PTS Granada, Granada, Spain
| | - Rosario del Moral
- Complejo Hospitalario de Granada, Servicio Andaluz de Salud, PTS Granada, Granada, Spain
| | - Francisco O'Valle
- Centro de Investigación Biomédica, Instituto Universitario de Investigación en Biopatología y Medicina Regenerativa, PTS Granada, Granada, Spain
- CIBERONC (Instituto de Salud Carlos III), Granada, Spain
- Instituto de Parasitología y Biomedicina “López Neyra”, Consejo Superior de Investigaciones Científicas, PTS Granada, Granada, Spain
- Departamento de Anatomía Patológica, Facultad de Medicina, Universidad de Granada, PTS Granada, Granada, Spain
| | - José Expósito
- Complejo Hospitalario de Granada, Servicio Andaluz de Salud, PTS Granada, Granada, Spain
| | - Francisco Javier Oliver
- CIBERONC (Instituto de Salud Carlos III), Granada, Spain
- Instituto de Parasitología y Biomedicina “López Neyra”, Consejo Superior de Investigaciones Científicas, PTS Granada, Granada, Spain
| | - José Mariano Ruiz de Almodóvar
- Centro de Investigación Biomédica, Instituto Universitario de Investigación en Biopatología y Medicina Regenerativa, PTS Granada, Granada, Spain
- CIBERONC (Instituto de Salud Carlos III), Granada, Spain
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Adipose tissue grafting for management of persistent anastomotic leak after low anterior resection. Tech Coloproctol 2019; 23:981-985. [PMID: 31617034 DOI: 10.1007/s10151-019-02095-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2019] [Accepted: 09/17/2019] [Indexed: 10/25/2022]
Abstract
BACKGROUND An anastomotic leak is the most dreaded complication after low anterior resection. Adipose tissue grafting may induce healing in a persistent anastomotic defect. The aim of the present study was to report retrospectively reviewed outcomes for a series of patients who were managed with heterotopic grafted adipose tissue to facilitate anastomotic healing. METHODS Patients with anastomotic leakage after low anterior resection sequentially treated with grafting of adipose tissue were included in the study. All patients had pelvic radiation during treatment and had a diverting ileostomy in situ. The cohort had a persistent defect despite being treated with available modalities such as suture repair, fibrin glue, Endo-Sponge and surgical debridement. The outcomes were reviewed and reported. RESULTS There were 11 patients (8 males and 3 females) with a median age of 54 years (range 33-72 years). Five patients experienced complete healing of the anastomotic defect with successful reversal of the diverting ileostomy. The anastomotic defect of one other patient in the series appeared to have healed and hence his diverting ileostomy was reversed. However, he presented with a recurrent leak, which ultimately necessitated an abdominoperineal resection. Another patient had a persistent defect after an attempt at adipose tissue grafting and opted to proceed with a takedown of the anastomosis. In the remaining four patients, the outcome after adipose tissue grafting remains unknown, as two patients succumbed to metastatic disease, one was lost to follow-up and the remaining patient developed a recurrence which required pelvic exenteration. Procedural associated morbidity occurred in one patient who developed fat embolism, which was treated expectantly. CONCLUSIONS Adipose tissue grafting is safe and feasible, though its effectiveness remains uncertain. It may be useful selectively in the management of persistent anastomotic leak after radiation and low anterior resection.
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Alvarenga V, Silva PTD, Bonfá ND, Pêgo B, Nanini H, Bernardazzi C, Madi K, Baetas da Cruz W, Castelo-Branco MT, de Souza HSP, Schanaider A. Protective effect of adipose tissue-derived mesenchymal stromal cells in an experimental model of high-risk colonic anastomosis. Surgery 2019; 166:914-925. [PMID: 31519305 DOI: 10.1016/j.surg.2019.07.023] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2019] [Revised: 06/20/2019] [Accepted: 07/11/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Dehiscence of intestinal anastomosis results in high morbidity and mortality. The aim of this study was to investigate the effects of locally administered adipose tissue-derived mesenchymal stromal cells in a model of high-risk colonic anastomosis in rats. METHODS Seven days after induction of colitis with 2,4,6-trinitrobenzene sulfonic acid, Wistar rats were submitted to a transection of the descending colon followed by end-to-end anastomosis and were then treated with 2×106 adipose tissue-derived mesenchymal stromal cells (from the preperitoneal fat) or an acellular culture solution instilled onto the surface of the anastomosis. At day 14, after macroscopic survey of the abdominal cavity, the anastomotic area was submitted to histologic and immunohistochemical analysis, evaluation of myeloperoxidase activity, fibrosis, epithelial integrity, NF-κ B activation, expression of inflammatory cytokines, and extracellular matrix-related genes. RESULTS Anastomotic leakage and mortality associated with high-risk anastomosis decreased with treatment with adipose tissue-derived mesenchymal stromal cells (P < .03). Application of adipose tissue-derived mesenchymal stromal cells resulted in lower histologic scores (P = .011), decreased deposition of collagen fibers (P = .003), preservation of goblet cells (P = .033), decreased myeloperoxidase activity (P = .012), decreased accumulation of CD4+ T-cells (P = .014) and macrophages (P = .011) in the lamina propria, a decrease in the number of apoptotic cells (P = .008), and the activation of NF-κ B (P = .036). Overexpression of IL-17, TNF-α , IFN-γ, and metalloproteinases in the acellular culture solution-treated, high-risk anastomosis group decreased (P < .05) to near normal values with adipose tissue-derived mesenchymal stromal cells treatment. CONCLUSION Improvements in outcomes of a high-risk colonic anastomosis with adipose tissue-derived mesenchymal stromal cells therapy reflect the immunomodulatory activity and healing effect of these cells, even after just topical administration and reinforces their use in future translational research.
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Affiliation(s)
- Valter Alvarenga
- Centro de Cirurgia Experimental, Programa de Pós-Graduação em Ciências Cirúrgicas, Departamento de Cirurgia, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | | | | | - Beatriz Pêgo
- Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Brazil
| | - Hayandra Nanini
- Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Brazil
| | - Cláudio Bernardazzi
- Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Brazil
| | - Kalil Madi
- Departamento de Patologia, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Wagner Baetas da Cruz
- Laboratório Translacional em Fisiologia Molecular (LabTrans) do Centro de Cirurgia Experimental, Departamento de Cirurgia, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Morgana Teixeira Castelo-Branco
- Laboratório de Imunologia Celular, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | | | - Alberto Schanaider
- Centro de Cirurgia Experimental, Programa de Pós-Graduação em Ciências Cirúrgicas, Departamento de Cirurgia, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
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Mazini L, Rochette L, Amine M, Malka G. Regenerative Capacity of Adipose Derived Stem Cells (ADSCs), Comparison with Mesenchymal Stem Cells (MSCs). Int J Mol Sci 2019; 20:ijms20102523. [PMID: 31121953 PMCID: PMC6566837 DOI: 10.3390/ijms20102523] [Citation(s) in RCA: 248] [Impact Index Per Article: 41.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Revised: 05/03/2019] [Accepted: 05/06/2019] [Indexed: 12/13/2022] Open
Abstract
Adipose tissue is now on the top one of stem cell sources regarding its accessibility, abundance, and less painful collection procedure when compared to other sources. The adipose derived stem cells (ADSCs) that it contains can be maintained and expanded in culture for long periods of time without losing their differentiation capacity, leading to large cell quantities being increasingly used in cell therapy purposes. Many reports showed that ADSCs-based cell therapy products demonstrated optimal efficacy and efficiency in some clinical indications for both autologous and allogeneic purposes, hence becoming considered as potential tools for replacing, repairing, and regenerating dead or damaged cells. In this review, we analyzed the therapeutic advancement of ADSCs in comparison to bone marrow (BM) and umbilical cord (UC)-mesenchymal stem cells (MSCs) and designed the specific requirements to their best clinical practices and safety. Our analysis was focused on the ADSCs, rather than the whole stromal vascular fraction (SVF) cell populations, to facilitate characterization that is related to their source of origins. Clinical outcomes improvement suggested that these cells hold great promise in stem cell-based therapies in neurodegenerative, cardiovascular, and auto-immunes diseases.
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Affiliation(s)
- Loubna Mazini
- Laboratoire Cellules Souches et Ingénierie Tissulaire, Centre Interface Applications Médicales CIAM, Université Mohammed VI polytechnique, Ben Guérir 43150, Morocco.
| | - Luc Rochette
- Equipe d'Accueil (EA 7460), Physiopathologie et Epidémiologie Cérébro-Cardiovasculaires (PEC2), Université de Bourgogne Franche Comté, Faculté des Sciences de Santé, 7 Bd Jeanne d'Arc, 21000 Dijon, France.
| | - Mohamed Amine
- Laboratoire d'Epidémiologie et de Biostatique, Centre Interface Applications Médicales CIAM, Université Mohammed VI polytechnique, Ben Guérir 43150, Morocco.
- Département de Santé Publique et de Médecine Communautaire, Faculté de Médecine et de Pharmacie, Université Cadi Ayyad, Marrakech 40000, Morocco.
| | - Gabriel Malka
- Laboratoire Cellules Souches et Ingénierie Tissulaire, Centre Interface Applications Médicales CIAM, Université Mohammed VI polytechnique, Ben Guérir 43150, Morocco.
- Laboratoire d'Epidémiologie et de Biostatique, Centre Interface Applications Médicales CIAM, Université Mohammed VI polytechnique, Ben Guérir 43150, Morocco.
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Mazini L, Rochette L, Amine M, Malka G. Regenerative Capacity of Adipose Derived Stem Cells (ADSCs), Comparison with Mesenchymal Stem Cells (MSCs). Int J Mol Sci 2019. [PMID: 31121953 DOI: 10.3390/ijms20102523.pmid:31121953;pmcid:pmc6566837] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/08/2023] Open
Abstract
Adipose tissue is now on the top one of stem cell sources regarding its accessibility, abundance, and less painful collection procedure when compared to other sources. The adipose derived stem cells (ADSCs) that it contains can be maintained and expanded in culture for long periods of time without losing their differentiation capacity, leading to large cell quantities being increasingly used in cell therapy purposes. Many reports showed that ADSCs-based cell therapy products demonstrated optimal efficacy and efficiency in some clinical indications for both autologous and allogeneic purposes, hence becoming considered as potential tools for replacing, repairing, and regenerating dead or damaged cells. In this review, we analyzed the therapeutic advancement of ADSCs in comparison to bone marrow (BM) and umbilical cord (UC)-mesenchymal stem cells (MSCs) and designed the specific requirements to their best clinical practices and safety. Our analysis was focused on the ADSCs, rather than the whole stromal vascular fraction (SVF) cell populations, to facilitate characterization that is related to their source of origins. Clinical outcomes improvement suggested that these cells hold great promise in stem cell-based therapies in neurodegenerative, cardiovascular, and auto-immunes diseases.
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Affiliation(s)
- Loubna Mazini
- Laboratoire Cellules Souches et Ingénierie Tissulaire, Centre Interface Applications Médicales CIAM, Université Mohammed VI polytechnique, Ben Guérir 43150, Morocco.
| | - Luc Rochette
- Equipe d'Accueil (EA 7460), Physiopathologie et Epidémiologie Cérébro-Cardiovasculaires (PEC2), Université de Bourgogne Franche Comté, Faculté des Sciences de Santé, 7 Bd Jeanne d'Arc, 21000 Dijon, France.
| | - Mohamed Amine
- Laboratoire d'Epidémiologie et de Biostatique, Centre Interface Applications Médicales CIAM, Université Mohammed VI polytechnique, Ben Guérir 43150, Morocco.
- Département de Santé Publique et de Médecine Communautaire, Faculté de Médecine et de Pharmacie, Université Cadi Ayyad, Marrakech 40000, Morocco.
| | - Gabriel Malka
- Laboratoire Cellules Souches et Ingénierie Tissulaire, Centre Interface Applications Médicales CIAM, Université Mohammed VI polytechnique, Ben Guérir 43150, Morocco.
- Laboratoire d'Epidémiologie et de Biostatique, Centre Interface Applications Médicales CIAM, Université Mohammed VI polytechnique, Ben Guérir 43150, Morocco.
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