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Stem cell therapy applied for digestive anastomosis: Current state and future perspectives

World Journal of Stem Cells 2022年第1期14卷 117-141页

作者： Jacobo Trébol Tihomir Georgiev-Hristov Isabel Pascual-Miguelañez Hector Guadalajara mariano garcía-arranz Damian garcía-Olmo Servicio de Cirugía General y del Aparato Digestivo Complejo Asistencial Universitario de SalamancaSalamanca 37007Spain Departamento de Anatomía e Histología Humanas Universidad de SalamancaSalamanca 37007Spain Servicio de Cirugía General y del Aparato Digestivo Hospital General Universitario de VillalbaMadrid 28400Spain Servicio de Cirugía General y del Aparato Digestivo Hospital Universitario La PazMadrid 28046Spain Servicio de Cirugía General y del Aparato Digestivo Hospital Universitario Fundación Jiménez DíazMadrid 28040Spain Grupo de Investigación en Nuevas Terapias Instituto de Investigación Sanitaria-Fundación Jiménez DíazMadrid 28040Spain Damian garcía-Olmo Departamento de CirugíaUniversidad Autónoma de MadridMadrid 28029Spain Servicio de Cirugía General y del Aparato Digestivo Hospital Universitario Fundación Jiménez Díaz y Grupo Quiron-Salud MadridMadrid 28040Spain

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.METHODS 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 biosutur

关键词： Surgical anastomosis Anastomotic leak Digestive system surgical procedure Cell transplantation Cell therapy Stem cells Tissue engineering

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Stem cell therapy for faecal incontinence: Current state and future perspectives

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World Journal of Stem Cells 2018年第7期10卷 82-105页

作者： Jacobo Trébol Ana Carabias-Orgaz mariano garcía-arranz Damián garcía-Olmo General and Digestive Tract Surgery Department Salamanca University Healthcare Centre Anaesthesiology Department Complejo Asistencial de ávila New Therapies Laboratory Instituto de Investigación Sanitaria-Fundación Jiménez Díaz General and Digestive Tract Surgery Department Quiron-Salud Hospitals Surgery Department Universidad AutónomaMadrid

Faecal continence is a complex function involving different organs and systems. Faecal incontinence is a common disorder with different pathogeneses, disabling consequences and high repercussions for quality of life. Current management modalities are not ideal, and the development of new treatments is needed. Since 2008, stem cell therapies have been validated, 36 publications have appeared(29 in preclinical models and seven in clinical settings), and six registered clinical trials are currently ongoing. Some publications have combined stem cells with bioengineering technologies. The aim of this review is to identify and summarise the existing published knowledge of stem cell utilization as a treatment for faecal incontinence. A narrative or descriptive review is presented. Preclinical studies have demonstrated that cellular therapy, mainly in the form of local injections of muscle-derived(muscle derived stem cells or myoblasts derived from them) or mesenchymal(bone-marrow-or adipose-derived) stem cells, is safe. Cellular therapy has also been shown to stimulate the repair of both acute and subacute anal sphincter injuries, and some encouraging functional results have been obtained. Stem cells combined with normal cells on bioengineered scaffolds have achieved the successful creation and implantation of intrinsically-innervated anal sphincter constructs. The clinical evidence, based on adipose-derived stem cells and myoblasts, is extremely limited yet has yielded some promising results, and appears to be safe. Further investigation in both animal models and clinical settings is necessary to drawing conclusions. Nevertheless, if the preliminary results are confirmed, stem cell therapy for faecal incontinence may well become a clinical reality in the near future.

关键词： Faecal incontinence Anal sphincter Cell implantation Tissue engineering Cell therapy Stem cells

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Rat model of anal sphincter injury and two approaches for stem cell administration

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World Journal of Stem Cells 2018年第1期10卷 1-14页

作者： Jacobo Trébol Tihomir Georgiev-Hristov Luz Vega-Clemente Ignacio garcía-Gómez Ana Carabias-Orgaz mariano garcía-arranz Damián garcía-Olmo Department of General and Digestive Tract Surgery University Hospital“La Paz”Madrid 28046Spain Department of General and Digestive Tract Surgery Villalba General HospitalMadrid 28400Spain New Therapies Laboratory Instituto de Investigación Sanitaria-Fundación Jiménez DíazMadrid 28040Spain Hektoen Institute of Medicine ChicagoIL 60612United States Department of Anaesthesiology Complejo Asistencial deávilaávila 05004Spain New Therapies Laboratory Instituto de Investigación Sanitaria-Fundación Jiménez DíazMadrid 28040Spain Department of General and Digestive Tract Surgery Quiron-Salud HospitalsMadrid 28040Spain Department of Surgery Madrid Autonomous UniversityMadrid 28029Spain

AIM To establish a rat model of anal sphincter injury and test different systems to provide stem cells to injured area.METHODS Adipose-derived stem cells(ASCs) were isolated from BDIX rats and were transfected with green fluorescent protein(GFP) for cell tracking. Biosutures(sutures covered with ASCs) were prepared with 1.5 × 10~6 GFPASCs, and solutions of 10~6 GFP-ASCs in normal saline were prepared for injection. Anorectal normal anatomy was studied on Wistar and BDIX female rats. Then, we designed an anal sphincter injury model consisting of a 1-cm extra-mucosal miotomy beginning at the anal verge in the anterior middle line. The sphincter lesion was confirmed with conventional histology(hematoxylin and eosin) and immunofluorescence with 4', 6-diamidino-2-phenylindole(commonly known as DAPI), GFP and α-actin. Functional effect was assessed with basal anal manometry, prior to and after injury. After sphincter damage, 36 BDIX rats were randomized to three groups for:(1) Cell injection without repair;(2) biosuture repair; and(3) conventional suture repair and cell injection. Functional and safety studies were conducted on all the animals. Rats were sacrificed after 1, 4 or 7 d. Then, histological and immunofluorescence studies were performed on the surgical area.RESULTS With the described protocol, biosutures had been covered with at least 820000-860000 ASCs, with 100% viability. Our studies demonstrated that some ASCs remained adhered after suture passage through the muscle. Morphological assessment showed that the rat anal anatomy is comparable with human anatomy; two sphincters are present, but the external sphincter is poorly developed. Anal sphincter pressure data showed spontaneous, consistent, rhythmic anal contractions, taking the form of "plateaus" with multiple twitches(peaks) in each pressure wave. These basal contractions were very heterogeneous; their frequency was 0.91-4.17 per min(mean 1.6980, SD 0.57698), their mean duration was 26.67 s and mean number of peaks was 12.53. Our morphological assessm

关键词： Fecal incontinence Experimental rat model Anal sphincter Cell implantation Cell therapy Stem cells Mesenchymal stem cell

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Detection of KRAS G12D in colorectal cancer stool by droplet digital PCR

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World Journal of Gastroenterology 2017年第39期23卷 7087-7097页

作者： Susana Olmedillas-López Dennis César Lévano-Linares Carmen Laura Aúz Alexandre Luz Vega-Clemente Edurne León Sánchez Alejandro Villagrasa Jaime Ruíz-Tovar mariano garcía-arranz Damián garcía-Olmo Foundation Health Research Institute-Fundación Jiménez Díaz University Hospital Department of Surgery School of Medicine Universidad Autónoma de Madrid Department of Surgery Rey Juan Carlos University Hospital Department of Pathology Fundación Jiménez Díaz University Hospital Department of Biomedicine and Biotechnology Universidad de Alcalá Department of Surgery Fundación Jiménez Díaz University Hospital

AIM To assess KRAS G12 D mutation detection by droplet digital PCR(dd PCR) in stool-derived DNA from colorectal cancer(CRC) patients.METHODS In this study, tumor tissue and stool samples were collected from 70 patients with stage Ⅰ-Ⅳ CRC diagnosed by preoperative biopsy. KRAS mutational status was determined by pyrosequencing analysis of DNA obtained from formalin-fixed paraffinembedded(FFPE) tumor tissues. The KRAS G12 D mutation was then analyzed by dd PCR in FFPE tumors and stool-derived DNA from patients with this point mutation. Wild-type(WT) tumors, as determined by pyrosequencing, were included as controls; analysis of FFPE tissue and stool-derived DNA by dd PCR was performed for these patients as well.RESULTS Among the total 70 patients included, KRAS mutations were detected by pyrosequencing in 32(45.71%), whereas 38(54.29%) had WT tumors. The frequency of KRAS mutations was higher in left-sided tumors(11 located in the right colon, 15 in the left, and 6 in the rectum). The predominant point mutation was KRAS G12 D(14.29%, n = 10), which was more frequent in early-stage tumors(I-IIA, n = 7). In agreement with pyrosequencing results, the KRAS G12 D mutation was detected by dd PCR in FFPE tumor-derived DNA, and only a residual number of mutated copies was found in WT controls. The KRAS G12 D mutation was also detected in stool-derived DNA in 80% of all fecal samples from CRC patients with this point mutation. CONCLUSION dd PCR is a reliable and sensitive method to analyze KRAS G12 D mutation in stool-derived DNA from CRC patients, especially at early stages. This non-invasive approach is potentially applicable to other relevant biomarkers for CRC management.

关键词：微滴数字 PCR KRAS 凳子修理福尔马林嵌入石蜡 Pyrosequencing Colorectal 癌症

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Stem cell therapy in the management of shoulder rotator cuff disorders

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World Journal of Stem Cells 2015年第4期7卷 691-699页

作者： Maria Valencia Mora Miguel A Ruiz Ibán Jorge Díaz Heredia Raul Barco Laakso Ricardo Cuéllar mariano garcía arranz Unidad de Hombro y Codo Hospital Universitario Ramón y Cajal Hospital Universitario La Paz Departamento de Traumatología y Cirugía Ortopédica Hospital Universitario Donostia Instituto de Investigación Sanitaria Fundación Jiménez Diaz Departamento de Cirugía Universidad Autónoma de Madrid

Rotator cuff tears are frequent shoulder problems that are usually dealt with surgical repair. Despite improved surgical techniques, the tendon-to-bone healing rate is unsatisfactory due to difficulties in restoring the delicate transitional tissue between bone and tendon. It is essential to understand the molecular mechanisms that determine this failure. The study of the molecular environment during embryogenesis and during normal healing after injury is key in devising strategies to get a successful repair. Mesenchymal stem cells(MSC) can differentiate into different mesodermal tissues and have a strong paracrine, anti-inflammatory, immunoregulatory and angiogenic potential. Stem cell therapy is thus a potentially effective therapy to enhance rotator cuff healing. Promising results have been reported with the use of autologous MSC of different origins in animal studies: they have shown to have better healing properties, increasing the amount of fibrocartilage formation and improving the orientation of fibrocartilage fibers with less immunologic response and reduced lymphocyte infiltration. All these changes lead to an increase in biomechanical strength. However, animal research is still inconclusive and more experimental studies are needed before human application. Future directions include expanded stem cell therapy in combination with growth factors or different scaffolds as well as new stem cell types and gene therapy.

关键词： Rotator cuff Enthesis Biologic Stem cells

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A universal additive concept yields record-high efficient organic solar cells

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Science China Materials 2024年第5期67卷 1670-1671页

作者： mariano Campoy Quiles Institute of Materials Science of Barcelona ICMAB-CSICCampus UAB08193BellaterraSpain

Organic photovoltaics(OPVs)are an emerging light-to-electricity conversion technology that promises flexible,lightweight,semitransparent devices based on abundant and non-toxic organic semiconductors.OPV power conversion efficiency under one sun has been increasing at an average pace of approximately 1%every year over the past 10 years,up to current values circa 20%.This has been possible through the continuous synthesis of improved semiconductors.

关键词： additive semiconductors approximate

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Quality assessment of the Topo-Iberia CGPS stations and data quality's effects on postfit ionosphere-free phase residuals

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Geodesy and Geodynamics 2024年第2期15卷 189-199页

作者： Juan A.garcía-Armenteros Center for Advanced Studies in Earth Sciences Energy and Environment(CEACTEMA)University of Jaén23071 JaenSpain

This paper analyzed GPS data from the Topo-Iberia network spanning almost 12 years(2008-2020).The data quality information for all 26 Topo-Iberia stations is provided for the first time,complementing the Spanish Geological Survey’s storage work.Data analyses based on quality indicators obtained using TEQC have been carried out.The guidelines and data quality information from the IGS stations have been considered as the quality references,with the stations ALJI,EPCU,and TIOU standing out as the worst stations,while on the contrary,FUEN,PALM,PILA,and TRIA meet the quality requirements to become an IGS station.The relationship between the GPS data quality and their GAMIT-and Gipsy X-derived postfit ionosphere-free phase residuals has also been investigated,and the results reveal an inversely proportional relationship.It has been found that the stations showing an increase in elevation of the horizon line,also show an increase in cycle slips and multipath,are among the poorest quality stations,and among those with the highest postfit RMS of phase residuals.Moreover,the evolution of the vegetation around the antenna should be considered as it could cause a progressive loss of quality,which is not complying with the IGS standards.The quality assessment shows that the Topo-Iberia stations are appropriate for geodetic purposes,but permanent monitoring would be necessary to avoid the least possible loss of data and quality.In addition,a method to characterize the GNSS data quality is proposed.

关键词： GPS dataquality's effects IGS quality standard Postfit LC phase residual Qualityassessment Topo-Iberia CGPS network

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Myelin histology:a key tool in nervous system research

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Neural Regeneration Research 2024年第2期19卷 277-281页

作者： Óscar Darío garcía-garcía Víctor Carriel Jesús Chato-Astrain Department of Histology Tissue Engineering GroupUniversity of Granada&Instituto de Investigación Biosanitaria ibs.GRANADAGranadaSpain

The myelin sheath is a lipoprotein-rich,multilayered structure capable of increasing conduction velocity in central and peripheral myelinated nerve fibers.Due to the complex structure and composition of myelin,various histological techniques have been developed over the centuries to evaluate myelin under normal,pathological or experimental conditions.Today,methods to assess myelin integrity or content are key tools in both clinical diagnosis and neuroscience research.In this review,we provide an updated summary of the composition and structure of the myelin sheath and discuss some histological procedures,from tissue fixation and processing techniques to the most used and practical myelin histological staining methods.Considering the lipoprotein nature of myelin,the main features and technical details of the different available methods that can be used to evaluate the lipid or protein components of myelin are described,as well as the precise ultrastructural techniques.

关键词： fluorescence microscopy histology light microscopy lipid histochemistry metallographic techniques myelin histochemistry myelin immunohistochemistry myelin structure&composition myelin ultrastructural evaluation tissue fixation&processing

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Interplay between mesenchymal stromal cells and the immune system after transplantation: implications for advanced cell therapy in the retina

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Neural Regeneration Research 2024年第3期19卷 542-547页

作者： María Norte-Muñoz David garcía-Bernal Diego garcía-Ayuso Manuel Vidal-Sanz Marta Agudo-Barriuso Grupo de Investigación Oftalmología Experimental Departamento de OftalmologíaOptometríaOtorrinolaringología y Anatomía PatológicaFacultad de MedicinaUniversidad de MurciaInstituto Murciano de Investigación Biosanitaria(IMIB)Campus de Ciencias de la Salud30120 MurciaSpain Grupo de Investigación Trasplante Hematopoyético y Terapia celular Departamento de Bioquímica e Inmunología.Facultad de MedicinaUniversidad de MurciaInstituto Murciano de Investigación Biosanitaria(IMIB)Campus de Ciencias de la Salud30120 MurciaSpain

Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical models.Mesenchymal stromal cells are well positioned as therapeutics because they address the underlying mechanisms of neurodegeneration,namely trophic factor deprivation and neuroinflammation.Most studies have focused on the beneficial effects of mesenchymal stromal cell transplantation on neuronal survival or functional improvement.However,little attention has been paid to the interaction between mesenchymal stromal cells and the host immune system due to the immunomodulatory properties of mesenchymal stromal cells and the long-held belief of the immunoprivileged status of the central nervous system.Here,we review the crosstalk between mesenchymal stromal cells and the immune system in general and in the context of the central nervous system,focusing on recent work in the retina and the importance of the type of transplantation.

关键词： adaptive immunity cell therapy central nervous system immune system innate immunity mesenchymal stromal cells neuroregeneration preclinical studies retina transplantation

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Navigating the controversy regarding antibiotic prophylaxis in acute variceal bleeding

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World Journal of Gastroenterology 2024年第18期30卷 2485-2487页

作者： David Aguirre-Villarreal Ignacio garcía-Juárez Department of Gastroenterology and Liver Transplant Unit Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico City 14080Mexico

Antibiotic prophylaxis in patients with cirrhosis and acute variceal bleeding is part of the standard of care according to most clinical guidelines.However,with recent evidence arguing against antibiotic prophylaxis,t... 详细信息

关键词： Cirrhosis Acute variceal bleeding Antibiotic prophylaxis Endoscopic band ligation Spontaneous bacterial peritonitis

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