Omar T F Ahmed, Ziyad Tarek Ahmed, Abdulrahman W Dairi, Maha Saad Zain Al-Abeden, Mohammed H Alkahlot, Rana H Alkahlot, Ghazi I Al Jowf, Lars M T Eijssen, Khawaja Husnain Haider
{"title":"The inconclusive superiority debate of allogeneic versus autologous MSCs in treating patients with HFrEF: a systematic review and meta-analysis of RCTs.","authors":"Omar T F Ahmed, Ziyad Tarek Ahmed, Abdulrahman W Dairi, Maha Saad Zain Al-Abeden, Mohammed H Alkahlot, Rana H Alkahlot, Ghazi I Al Jowf, Lars M T Eijssen, Khawaja Husnain Haider","doi":"10.1186/s13287-025-04209-5","DOIUrl":"https://doi.org/10.1186/s13287-025-04209-5","url":null,"abstract":"<p><strong>Background: </strong>Recent randomized controlled trials have consistently demonstrated the safety and potential efficacy of MSC therapy for heart failure patients. This study delves into mesenchymal stem cells' promising potential, offering a beacon of hope for the future of heart failure treatment with reduced ejection fraction (HFrEF).</p><p><strong>Methods: </strong>We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for this systematic review and meta-analysis. We searched four databases and registers for RCTs, including PubMed, EBSCO, clinicaltrials.gov, ICTRP, and other relevant websites. We then selected thirteen RCTs with 1184 participants based on our pre-defined inclusion/exclusion criteria. Two independent assessors extracted the data and performed a quality assessment. The data were then plotted for various outcomes, including death, hospitalization, major adverse cardiac events, pump function parameters, and 6-min walk distance.</p><p><strong>Results: </strong>The safety of MSC-based treatment has been consistently demonstrated with MSCs from autologous (<sup>Auto</sup>MSCs) and allogeneic (<sup>Allo</sup>MSCs) sources. This reassuring finding underscores the reliability of MSC-based therapy irrespective of their source. However, <sup>Auto</sup>MSCs showed a trend toward greater protective benefits. Subgroup analysis revealed no significant differences between <sup>Auto</sup>MSCs and <sup>Allo</sup>MSCs in improving LVEF; 0.86% (95% CI - 1.21-2.94%) for <sup>Allo</sup>MSCs versus 2.17% (- 0.48%; 95% CI - 1.33-5.67%) for <sup>Auto</sup>MSCs. <sup>Allo</sup>MSCs significantly reduced end-diastolic volume (LVEDV) by - 2.08 mL (95% CI - 3.52-0.64 mL). Only <sup>Allo</sup>MSCs significantly improved 6-min walking distance (6-MWD); 31.88 m (95% CI 5.03-58.74 m) for <sup>Allo</sup>MSCs versus 31.71 m (95% CI - 8.91-71.25 m) for <sup>Auto</sup>MSCs. The exclusion of studies using adipose-derived cells resulted in even better safety and a significant improvement in LVEF for <sup>Allo</sup>MSCs treatment.</p><p><strong>Conclusion: </strong>Our findings suggest that <sup>Allo</sup>MSCs are at par with <sup>Auto</sup>MSCs in improving functional outcomes in heart failure patients. This underscores the need for future investigations in a larger patient cohort, emphasizing the urgency and importance of further research to fully understand the potential of MSCs in treating heart failure.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"175"},"PeriodicalIF":7.1,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11993956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144044517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lucie Janeckova, Monika Stastna, Dusan Hrckulak, Linda Berkova, Jan Kubovciak, Jakub Onhajzer, Vitezslav Kriz, Stela Dostalikova, Tereza Mullerova, Katerina Vecerkova, Marketa Tenglerova, Stepan Coufal, Klara Kostovcikova, Richard S Blumberg, Dominik Filipp, Konrad Basler, Tomas Valenta, Michal Kolar, Vladimir Korinek
{"title":"Tcf4 regulates secretory cell fate decisions in the small intestine and colon tumors: insights from transcriptomic, histological, and microbiome analyses.","authors":"Lucie Janeckova, Monika Stastna, Dusan Hrckulak, Linda Berkova, Jan Kubovciak, Jakub Onhajzer, Vitezslav Kriz, Stela Dostalikova, Tereza Mullerova, Katerina Vecerkova, Marketa Tenglerova, Stepan Coufal, Klara Kostovcikova, Richard S Blumberg, Dominik Filipp, Konrad Basler, Tomas Valenta, Michal Kolar, Vladimir Korinek","doi":"10.1186/s13287-025-04280-y","DOIUrl":"https://doi.org/10.1186/s13287-025-04280-y","url":null,"abstract":"<p><strong>Background: </strong>The canonical Wnt signaling pathway controls the continuous renewal of the intestinal epithelium and the specification of epithelial cell lineages. Tcf4, a nuclear mediator of Wnt signaling, is essential for the differentiation and maintenance of Paneth cells in the small intestine. Its deficiency is associated with reduced expression of key α-defensins, highlighting its role in host-microbe interactions. However, the exact function of Tcf4 in specifying the secretory lineage and its contribution to antimicrobial peptide production remain incompletely understood. Remarkably, α-defensin expression has also been detected in human colon adenomas, where aberrant Wnt signaling is a hallmark. This raises important questions: What is the role of these Paneth-like cells in tumor biology, and how does Tcf4 influence their identity and function?</p><p><strong>Methods: </strong>We investigated cell specification in small intestinal crypts and colon tumors using conditional Tcf7l2 deletion, cell type-specific Cre recombinases, and reporter alleles in mice. Transcriptomic (single-cell and bulk RNA sequencing) and histological analyses were performed and complemented by microbiome profiling, antibiotic treatment, and intestinal organoids to functionally validate the main findings.</p><p><strong>Results: </strong>The inactivation of Tcf4 depletes Paneth cells and antimicrobial peptides, disrupting the gut microbiota balance. In secretory progenitors, loss of Tcf4 shifts differentiation toward goblet cells. In the small intestine, alternative secretory progenitors produce Wnt ligands to support stem cells and epithelial renewal in the absence of Paneth cells. In colon tumors, Paneth-like cells form a tumor cell population, express Wnt ligands, and require Tcf4 for their identity. Loss of Tcf4 redirects their differentiation toward goblet cells.</p><p><strong>Conclusions: </strong>Tcf4 controls the balance between Paneth and goblet cells and is essential for antimicrobial peptide production in the small intestine. In colon adenomas, Paneth-like tumor cells drive antimicrobial gene expression and provide Wnt3 ligands, which may have implications for cancer therapy.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"170"},"PeriodicalIF":7.1,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11993999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sona Zare, Alireza Jafarzadeh, Solmaz Zare, Amir Shamloo
{"title":"Exploring the dermatological applications of human mesenchymal stem cell secretome: a comprehensive review.","authors":"Sona Zare, Alireza Jafarzadeh, Solmaz Zare, Amir Shamloo","doi":"10.1186/s13287-025-04311-8","DOIUrl":"https://doi.org/10.1186/s13287-025-04311-8","url":null,"abstract":"<p><strong>Introduction: </strong>Mesenchymal stem cell (MSC)-derived conditioned media is emerging as a promising alternative to stem cell therapy, owing to its abundant content of growth factors and cytokines.</p><p><strong>Objective: </strong>This review evaluates the clinical applications of MSC-conditioned media in improving scars, promoting wound healing, stimulating hair growth, and rejuvenating the skin.</p><p><strong>Materials and methods: </strong>A thorough search of relevant databases was performed to identify studies meeting the inclusion criteria. From an initial pool of 75 articles, 16 studies published up to 2024 were selected based on their relevance, focus, and alignment with the research objectives.</p><p><strong>Results: </strong>Among the 17 selected studies, 5 examined the role of conditioned media in skin rejuvenation, 3 investigated its effects on hair growth, 5 assessed its efficacy in scar treatment, 2 assessed its efficacy in Inflammatory Dermatologic Disease and 2 explored its role in wound healing. All studies reported favorable outcomes, demonstrating significant improvements in scars, hair regrowth, and skin rejuvenation with the application of conditioned media.</p><p><strong>Conclusion: </strong>This review underscores the potential of MSC-derived conditioned media in dermatology. Several studies also highlighted its enhanced therapeutic effects when combined with adjunctive treatments, such as laser therapy and microneedling, showcasing improved outcomes in dermatological care.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"177"},"PeriodicalIF":7.1,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11993991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144010746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Harnessing stem cell therapeutics in LPS-induced animal models: mechanisms, efficacies, and future directions.","authors":"Chengran Wang, Fanghong Ge, Fangjun Ge, Zhonghang Xu, Jinlan Jiang","doi":"10.1186/s13287-025-04290-w","DOIUrl":"https://doi.org/10.1186/s13287-025-04290-w","url":null,"abstract":"<p><p>The severity and threat posed by inflammation are well documented, and lipopolysaccharides (LPS), as important inducers of inflammatory responses, are widely recognized for studying host immunity and the resulting tissue and organ damage. The LPS-induced disease model, triggers a remarkable release of inflammatory factors, immune and coagulation dysfunction, and damage to vital organs such as the brain, lungs, heart, liver, and kidneys. Recently, the role of mesenchymal stem cells (MSCs) in various clinical diseases has garnered significant attention due to their immunomodulatory, anti-inflammatory, tissue healing, anti-apoptotic, and antibacterial properties. Despite the common use of LPS models to induce disease models and simulate acute inflammation, the integration of stem cell therapy within these models remains underexplored. This article integrates the LPS induced animal model and reviews the current evidence regarding the therapeutic mechanisms of stem cells in LPS-induced disease models across various human body systems. Furthermore, this review predicts and hypothesizes the feasibility and potential of using stem cells in disease models that have not yet been extensively studied, based on existing animal inflammation models.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"176"},"PeriodicalIF":7.1,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11993993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Small molecules direct the generation of ameloblast-like cells from human embryonic stem cells.","authors":"Ximei Zhu, YiMeng Zhao, Xiaofan Bai, Qiannan Dong, Chunli Tian, Ruilin Sun, Congjuan Yan, Jianping Ruan, Zhongbo Liu, Jianghong Gao","doi":"10.1186/s13287-025-04294-6","DOIUrl":"https://doi.org/10.1186/s13287-025-04294-6","url":null,"abstract":"<p><strong>Background: </strong>Ameloblasts present a promising avenue for the investigation of enamel and tooth regeneration. Previous protocols for directing the differentiation of human embryonic stem cells (hESCs) into dental epithelial (DE) cells involving the need for additional cells, conditional medium, and the use of costly cytokines. Importantly, ameloblasts have not been generated from hESCs in previous studies. Hence, we aimed to identify defined differentiation conditions that would solely utilize small molecules to achieve the production of ameloblasts.</p><p><strong>Methods: </strong>We developed a three-step strategy entailing the progression of hESCs through non-neural ectoderm (NNE) and DE to generate functional ameloblasts in vitro. Initially, the NNE fate was induced from hESCs using a 6-day differentiation protocol with 1 µmol/L Retinoic acid (RA). Subsequently, the NNE lineage was differentiated into DE by employing a combination of 1 µmol/L LDN193189 (a BMP signaling inhibitor) and 1 µmol/L XAV939 (a WNT signaling inhibitor). In the final phase, 3 µmol/L CHIR99021 (a WNT signaling activator) and 2 µmol/L DAPT (a NOTCH signaling inhibitor) were utilized to achieve the fate of ameloblasts from DE cells. Three-dimensional cultures were investigated to enhance the ameloblast differentiation ability of the induced DE cells. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunofluorescence were conducted to assess the expression of lineage-specific markers. Alizarin Red S (ARS) staining was performed to evaluate the formation of mineralization nodules.</p><p><strong>Results: </strong>The application of RA facilitated the efficient generation of NNE within a six-day period. Subsequently, upon stimulation with LDN193189 and XAV939, a notable emergence of DE cells was observed on the eighth days. By the tenth day, ameloblast-like cells derived from hESCs were generated. Upon cultivation in spheroids, these cells exhibited elevated levels of ameloblast markers AMBN and AMELX expression, suggesting that spheroid culture augments the differentiation of ameloblasts.</p><p><strong>Conclusion: </strong>We established an efficient small molecule-based method to differentiate hESCs into ameloblast-like cells through the concerted modulation of RA, BMP, WNT, and NOTCH signaling pathways, potentially advancing research in enamel and tooth regeneration.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"173"},"PeriodicalIF":7.1,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11993985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L Dalle Carbonare, M Cominacini, E Trabetti, C Bombieri, J Pessoa, M G Romanelli, M T Valenti
{"title":"The bone microenvironment: new insights into the role of stem cells and cell communication in bone regeneration.","authors":"L Dalle Carbonare, M Cominacini, E Trabetti, C Bombieri, J Pessoa, M G Romanelli, M T Valenti","doi":"10.1186/s13287-025-04288-4","DOIUrl":"https://doi.org/10.1186/s13287-025-04288-4","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs) play a crucial role in bone formation and remodeling. Intrinsic genetic factors and extrinsic environmental cues regulate their differentiation into osteoblasts. Within the bone microenvironment, a complex network of biochemical and biomechanical signals orchestrates bone homeostasis and regeneration. In addition, the crosstalk among MSCs, immune cells, and neighboring cells-mediated by extracellular vesicles and non-coding RNAs (such as circular RNAs and micro RNAs) -profoundly influences osteogenic differentiation and bone remodeling. Recent studies have explored specific signaling pathways that contribute to effective bone regeneration, highlighting the potential of manipulating the bone microenvironment to enhance MSC functionality. The integration of advanced biomaterials, gene editing techniques, and controlled delivery systems is paving the way for more targeted and efficient regenerative therapies. Furthermore, artificial intelligence could improve bone tissue engineering, optimize biomaterial design, and enable personalized treatment strategies. This review explores the latest advancements in bone regeneration, emphasizing the intricate interplay among stem cells, immune cells, and signaling molecules. By providing a comprehensive overview of these mechanisms and their clinical implications, we aim to shed light on future research directions in this rapidly evolving field.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"169"},"PeriodicalIF":7.1,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11993959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144052796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Z Du, A Bas-Cristóbal Menéndez, M Urban, A Hartley, D Ratsma, M Koedam, T P P van den Bosch, M Clahsen-van Groningen, J Gribnau, J Mulder, M E J Reinders, C C Baan, B van der Eerden, R P Harbottle, Martin J Hoogduijn
{"title":"Erythropoietin delivery through kidney organoids engineered with an episomal DNA vector.","authors":"Z Du, A Bas-Cristóbal Menéndez, M Urban, A Hartley, D Ratsma, M Koedam, T P P van den Bosch, M Clahsen-van Groningen, J Gribnau, J Mulder, M E J Reinders, C C Baan, B van der Eerden, R P Harbottle, Martin J Hoogduijn","doi":"10.1186/s13287-025-04282-w","DOIUrl":"https://doi.org/10.1186/s13287-025-04282-w","url":null,"abstract":"<p><strong>Background: </strong>The kidney's endocrine function is essential for maintaining body homeostasis. Erythropoietin (EPO) is one of the key endocrine factors produced by the kidney, and kidney disease patients frequently experience anemia due to impaired EPO production. In the present study we explored the potential of human induced pluripotent stem cell (iPSC)-derived kidney organoids to restore EPO production.</p><p><strong>Methods: </strong>EPO secretion by kidney organoids was examined under 1% and 20% oxygen levels. To increase the EPO secreting capacity of kidney organoids, iPSC were genetically engineered with a non-integrating scaffold/matrix attachment region (S/MAR) DNA vector containing the EPO gene and generated EPO-overexpressing (EPO+) kidney organoids. To assess the physiological effects of EPO + organoids, 2-8 organoids were implanted subcutaneously in immunodeficient mice.</p><p><strong>Results: </strong>Kidney organoids produced low amounts of EPO under 1% oxygen. EPO S/MAR DNA vectors persisted and continued to robustly express EPO during iPSC expansion and kidney organoid differentiation without interfering with cellular proliferation. EPO + iPSC demonstrated efficient differentiation into kidney organoids. One-month post-implantation, EPO + organoids displayed continuously elevated EPO mRNA levels and significantly increased endothelial cell numbers compared to control organoids. Hematocrit levels were notably elevated in mice implanted with EPO + organoids in an organoid number-dependent manner. EPO + organoids furthermore influenced bone homeostasis in their hosts, evidenced by a change in trabecular bone composition.</p><p><strong>Conclusion: </strong>Kidney organoids modified by EPO S/MAR DNA vector allow stable long-term delivery of EPO. The observed physiological effects following the implantation of EPO + organoids underscore the potential of gene-edited kidney organoids for endocrine restoration therapy.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"174"},"PeriodicalIF":7.1,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11993987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Editorial Expression of Concern: Any closer to successful therapy of multiple myeloma? CAR-T cell is a good reason for optimism.","authors":"","doi":"10.1186/s13287-025-04260-2","DOIUrl":"https://doi.org/10.1186/s13287-025-04260-2","url":null,"abstract":"","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"168"},"PeriodicalIF":7.1,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11987320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cell-based regenerative and rejuvenation strategies for treating neurodegenerative diseases.","authors":"Sixiu Deng, Huangfan Xie, Bingqing Xie","doi":"10.1186/s13287-025-04285-7","DOIUrl":"10.1186/s13287-025-04285-7","url":null,"abstract":"<p><p>Neurodegenerative diseases including Alzheimer's and Parkinson's disease are age-related disorders which severely impact quality of life and impose significant societal burdens. Cellular senescence is a critical factor in these disorders, contributing to their onset and progression by promoting permanent cell cycle arrest and reducing cellular function, affecting various types of cells in brain. Recent advancements in regenerative medicine have highlighted \"R3\" strategies-rejuvenation, regeneration, and replacement-as promising therapeutic approaches for neurodegeneration. This review aims to critically analyze the role of cellular senescence in neurodegenerative diseases and organizes therapeutic approaches within the R3 regenerative medicine paradigm. Specifically, we examine stem cell therapy, direct lineage reprogramming, and partial reprogramming in the context of R3, emphasizing how these interventions mitigate cellular senescence and counteracting aging-related neurodegeneration. Ultimately, this review seeks to provide insights into the complex interplay between cellular senescence and neurodegeneration while highlighting the promise of cell-based regenerative strategies to address these debilitating conditions.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"167"},"PeriodicalIF":7.1,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nerea Dominguez-Pinilla, Luis Ignacio González-Granado, Aitor Gonzaga, María López Diaz, Cecilia Castellano Yáñez, Clara Aymerich, Xabier Freire, Olga Ordoñez, Álvaro Gimeno Diaz de Atauri, María Salomé Albi Rodríguez, Elisa Martínez López, Rodrigo Iñiguez, Olga Serrano Garrote, Almudena Castro Frontiñán, Etelvina Andreu, Ana María Gutierrez-Vilchez, Marga Anton-Bonete, Gema Martinez-Navarrete, Nerea Castillo-Flores, Cristina Prat-Vidal, Margarita Blanco, Rocío Morante Valverde, Eduardo Fernandez, Sergi Querol, Luis Manuel Hernández-Blasco, Sylvia Belda-Hofheinz, Bernat Soria
{"title":"Consecutive intrabronchial administration of Wharton's jelly-derived mesenchymal stromal cells in ECMO-supported pediatric patients with end-stage interstitial lung disease: a safety and feasibility study (CIBA method).","authors":"Nerea Dominguez-Pinilla, Luis Ignacio González-Granado, Aitor Gonzaga, María López Diaz, Cecilia Castellano Yáñez, Clara Aymerich, Xabier Freire, Olga Ordoñez, Álvaro Gimeno Diaz de Atauri, María Salomé Albi Rodríguez, Elisa Martínez López, Rodrigo Iñiguez, Olga Serrano Garrote, Almudena Castro Frontiñán, Etelvina Andreu, Ana María Gutierrez-Vilchez, Marga Anton-Bonete, Gema Martinez-Navarrete, Nerea Castillo-Flores, Cristina Prat-Vidal, Margarita Blanco, Rocío Morante Valverde, Eduardo Fernandez, Sergi Querol, Luis Manuel Hernández-Blasco, Sylvia Belda-Hofheinz, Bernat Soria","doi":"10.1186/s13287-025-04289-3","DOIUrl":"10.1186/s13287-025-04289-3","url":null,"abstract":"<p><strong>Background: </strong>Patients ineligible for lung transplant with end-stage Interstitial Lung Disease (ILD) on Extra-Corporeal Membrane Oxygenation (ECMO) face an appalling prognosis with limited therapeutic options. Due to the beneficial effect of Mesenchymal Stromal Cells (MSC) on inflammatory, immunological and infectious diseases, cell therapy has been proposed as an option, but administration is hampered by the ECMO.</p><p><strong>Methods: </strong>Cryopreserved Wharton-jelly derived MSC (WJ-MSC) were conveniently diluted and directly applied consecutively on each lobule (5,1 ml = 10<sup>7</sup> cells) at a continuous slow rate infused over one hour via flexible bronchoscopy (Consecutive IntraBronchial Administration method, CIBA method).</p><p><strong>Results: </strong>Intrabronchial administration of MSC to a patient on ECMO was well tolerated by the patient even though it did not reverse the patient's ILD. This manuscript presents preliminary evidence from ongoing clinical trials program on Cell Therapy of Inflammatory, Immune and Infectious Diseases and, to our knowledge, is the first report of intrabronchial administration of MSC in a paediatric ECMO patient with ILD. Even more, MSC administered by this method do not reach the systemic circulation and do get blocked on ECMO membrane.</p><p><strong>Conclusions: </strong>Direct intrabronchial administration of MSC in a patient on ECMO is feasible and safe, and may be a new avenue to be assayed in ECMO patients with inflammatory, immunological and infectious diseases of the lung.</p>","PeriodicalId":21876,"journal":{"name":"Stem Cell Research & Therapy","volume":"16 1","pages":"164"},"PeriodicalIF":7.1,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143789087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}