American journal of stem cells最新文献

{"title":"A bioactive composite of freeze-dried stem cells, porous microcarriers, and fibrinogen-thrombin gel for dental pulp tissue engineering.","authors":"Mariam Z Kakabadze, Tamta Jikia, Teona Paresishvili, Lia Karalashvili, David Chakhunashvili, Merab Janelidze, Zurab Kakabadze","doi":"10.62347/RJPQ4886","DOIUrl":"10.62347/RJPQ4886","url":null,"abstract":"<p><strong>Background: </strong>The aim of this study was to develop a novel biocompatible composite for the regeneration of damaged dental pulp tissue.</p><p><strong>Materials and methods: </strong>To create the composite, porous microcarriers were loaded with freeze-dried bone marrow stem cells and embedded in a fibrinogen-thrombin gel. The regenerative potential of the composite was evaluated in both ectopic and orthotopic animal models of dental pulp injury.</p><p><strong>Results: </strong>The composite stimulated the migration and proliferation of host pulp cells via growth factors and cytokines secreted by freeze-dried bone marrow stem cells. Furthermore, the microcarrier-based scaffold created a three-dimensional microenvironment that preserved the paracrine activity of stem cells, promoting the effective regeneration of damaged or partially amputated dental pulp.</p><p><strong>Conclusion: </strong>This bioactive composite demonstrates significant potential for regenerative endodontics, facilitating the restoration of dental pulp. Further studies are needed to elucidate the specific role of paracrine factors from freeze-dried stem cells in improving pulp tissue regeneration.</p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"15 1","pages":"13-26"},"PeriodicalIF":1.9,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13006739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147508761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GDF11 activates AMPK-dependent mitophagy to drive osteogenic differentiation of rat bone marrow mesenchymal stem cells.","authors":"Xinfeng Gao, Qiting He, Junjun Chen, Gen Wu, Shaoqiang Xia, Shuaiwei Shang, Linghang Xue, Xinqiang Bei, Kai Xiao","doi":"10.62347/RLSG3699","DOIUrl":"10.62347/RLSG3699","url":null,"abstract":"<p><strong>Background: </strong>Growth differentiation factor 11 (GDF11) has emerged as a potential regulator of bone regeneration; however, the molecular mechanisms through which it influences osteogenic differentiation, particularly in relation to mitochondrial quality control, remain unclear. This study aimed to elucidate the role of adenosine monophosphate-activated protein kinase (AMPK)-dependent mitophagy in GDF11-mediated osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMMSCs).</p><p><strong>Methods: </strong>rBMMSCs were induced toward osteogenic differentiation with or without GDF11 treatment. To specifically inhibit AMPK-dependent mitophagy, Compound C, an AMPK inhibitor, was employed. Osteogenic differentiation was evaluated using alkaline phosphatase (ALP) staining and activity assays, while Alizarin Red S (ARS) staining was performed to assess matrix mineralization. The expression of Mitophagy- and osteogenesis-associated markers was analyzed through immunofluorescence staining, quantitative real-time PCR, and western blotting.</p><p><strong>Results: </strong>GDF11 significantly enhanced the osteogenic differentiation of rBMMSCs, as evidenced by increased ALP activity, more intense ALP staining, enhanced calcium nodule formation, and elevated expression of ALP and RUNX2. GDF11 activated mitochondrial function by promoting AMPK phosphorylation and inducing Mitophagy. Inhibition of AMPK significantly impaired Mitophagy, while Compound C-mediated blockade of AMPK-dependent mitophagy not only suppressed basal osteogenic differentiation but also abolished the pro-osteogenic effects of GDF11. This was reflected by a pronounced reduction in GDF11-induced ALP activity, mineralization, and the expression of key osteogenic genes at both the mRNA and protein levels.</p><p><strong>Conclusion: </strong>GDF11 enhances the osteogenic differentiation of rBMMSCs by activating AMPK-dependent mitophagy. These findings identify AMPK-dependent Mitophagy as a pivotal mechanism mediating the osteogenic actions of GDF11, providing new mechanistic insights that may guide the development of novel strategies for bone regeneration.</p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"15 1","pages":"1-12"},"PeriodicalIF":1.9,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13006738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147508852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First live births after adipose-derived stem cells and platelet-rich plasma intraovarian administration.","authors":"Zaher Merhi, Bhavika Garg, Jessica Haroun","doi":"10.62347/KWFR2442","DOIUrl":"10.62347/KWFR2442","url":null,"abstract":"<p><p>This report describes two women aged 45 and older who achieved live births following intraovarian administration of a novel combination of mechanically processed adipose nanofat rich in adipose-derived stem cells (ADSCs) and autologous platelet-rich plasma (PRP). Both patients had a history of prolonged infertility and multiple failed assisted reproductive technology cycles with in vitro fertilization (IVF). Case 1, a 46-year-old with diminished ovarian reserve and prior miscarriage, underwent adipose-PRP treatment after unsuccessful minimal stimulation IVF. Six months later, she conceived naturally and delivered a healthy infant at age 47. Case 2, a 45-year-old with endometriosis and multiple failed IVF attempts, conceived via frozen embryo transfer of her only euploid embryo produced three months after adipose-PRP treatment, resulting in the birth of a healthy infant. The combination approach was developed to comply with U.S. FDA minimal manipulation guidelines, avoiding enzymatic processing of adipose tissue. This report is, to our knowledge, the first to document natural conception in women with age over 45 following combined adipose nanofat ADSCs and PRP intraovarian injection, and among the few to describe live births at this age using autologous oocytes after such therapy. These findings suggest that adipose-PRP treatment may offer a promising regenerative option for women with extremely diminished ovarian reserve who desire genetically related offspring, though controlled studies are required to confirm long term safety, efficacy, and appropriate patient selection.</p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"14 5","pages":"277-283"},"PeriodicalIF":1.9,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12816867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of FN1 gene interference in neural differentiation of human bone marrow mesenchymal stem cells.","authors":"Buhe Buren, Chaoqian Han, Chenyuan Yang, Feng Li, Dongsheng Fan, Xiaolong Wang, Xiaosai Hou, Xiaoxu Liu, Shangfei Jing","doi":"10.62347/TCNJ7008","DOIUrl":"10.62347/TCNJ7008","url":null,"abstract":"<p><strong>Objective: </strong>Fibronectin 1 (FN1) encodes fibronectin, a protein essential for cell adhesion, migration, extracellular matrix assembly, and regulation of cell differentiation and proliferation. While FN1 has been implicated in osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), its role in neural differentiation remains unclear. This study aimed to investigate the effect of FN1 gene interference on neural differentiation of human BMSCs and explore the underlying molecular mechanisms.</p><p><strong>Method: </strong>Three small interfering RNAs (ssi-417, si-4467 and si-5468) targeting FN1 were designed and transfected into BMSCs undergoing neural differentiation. Morphological changes were observed, and FN1 expression was assessed at both mRNA and protein levels. Alkaline phosphatase (ALP) staining was performed, and the expression of neural differentiation-related markers (MAP2, Tuj1, NSE and DCX) was quantified. Transcriptome sequencing was used to identify differentially expressed genes (DEGs), alternative splicing (AS) events and key pathways. Protein-protein interaction (PPI) network analysis was conducted to identify hub genes.</p><p><strong>Result: </strong>Cells in the FN1 interference group retained a spindle-shaped mesenchymal morphology. FN1 expression at both mRNA and protein levels was significantly reduced in all three siRNA groups compared with the model group (<i>P</i> < 0.05). ALP staining showed a higher positive rate in the FN1 interference group. Expression of neural differentiation markers (MAP2, Tuj1, NSE and DCX) was significantly downregulated in the interference group compared with the model group (<i>P</i> < 0.05). Transcriptome analysis revealed 1047 upregulated and 1077 downregulated DEGs, enriched in pathways related to signal transduction, immune response, RNA processing, apoptosis and DNA repair. Additionally, 2246 alternative splicing events were identified, and PPI network analysis highlighted IL-6 as a core gene.</p><p><strong>Conclusion: </strong>FN1 gene interference inhibits neural differentiation of BMSCs and alters key signaling pathways and splicing patterns, suggesting that FN1 plays a critical role in regulating stem cell fate. These findings provide new insights into the molecular mechanisms underlying neural differentiation of BMSCs.</p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"14 4","pages":"201-216"},"PeriodicalIF":1.9,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12629971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145585686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and efficacy of allogeneic umbilical cord-derived mesenchymal stem cell transplantation in type 2 diabetes: a pilot clinical trial.","authors":"Ramin Raoufinia, Jalil Tavakol-Afshari, Mozhgan Afkhamizadeh, Ehsan Saburi, Amir Adhami Moghadam, Sareh Etemad, Hamid Reza Rahimi","doi":"10.62347/OPHF7871","DOIUrl":"10.62347/OPHF7871","url":null,"abstract":"<p><strong>Background: </strong>Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and β-cell dysfunction, with chronic inflammation playing a central pathogenic role. Mesenchymal stem cells (MSCs) possess therapeutic potential through immunomodulatory and tissue-reparative properties. This study aimed to evaluate the safety and efficacy of intravenous allogeneic umbilical cord-derived MSCs (UC-MSCs) in patients with T2DM.</p><p><strong>Methods: </strong>Eleven adults with T2DM (disease duration ≥ 10 years; HbA1c ≤ 8%) received a single intravenous infusion of 1 × 10⁸ UC-MSCs. This open-label pilot trial assessed safety (adverse events, hematologic and metabolic parameters) and efficacy (glycemic control and inflammatory gene expression) over a 2-month follow-up period. UC-MSCs were isolated under standardized conditions.</p><p><strong>Results: </strong>UC-MSC transplantation in patients with T2DM was well tolerated, with only transient fever (36.3%) and mild muscle pain (18.2%) reported. The intervention resulted in significant metabolic improvements, including a 2.1% reduction in HbA1c (P = 0.00095) and a decrease in fasting glucose by 93.7 mg/dL (P = 0.00097). Treatment also modulated inflammatory pathways, as evidenced by upregulating of IKBα (1.76-fold, P = 0.0067) and downregulating of TNFα (0.62-fold) and IL-6 (0.65-fold). Variability in IKBα expression accounted for 48% of the variance in HbA1c (r = -0.69). Two distinct response patterns were observed: improvement in insulin sensitivity (7/11) via NF-κB suppression, and enhancement of β-cell function (3/11).</p><p><strong>Conclusion: </strong>Allogeneic UC-MSC transplantation appears safe and significantly improves glycemic control in patients with T2DM. The heterogeneity in patient responses underscores the importance of stratification based on inflammatory status. These findings support UC-MSC therapy as a promising disease-modifying strategy and highlight the need for larger, controlled clinical trials.</p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"14 4","pages":"244-260"},"PeriodicalIF":1.9,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12629970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145585763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic growth factors preconditioning strategy to improve hepatic differentiation efficiency of UC-MSCs <i>in vitro</i>.","authors":"Zahid Habib Qureshi, Tahir Maqbool, Bakhtawar Farooq, Awais Altaf, Muzammal Mateen Azhar, Muhammad Rafiq, Muhammad Sarwar","doi":"10.62347/XFHZ3412","DOIUrl":"10.62347/XFHZ3412","url":null,"abstract":"<p><strong>Background: </strong>Liver diseases remain a major global health burden, with limited treatment options for advanced hepatic dysfunction. Stem cell-based therapies offer a favorable strategy for liver regeneration by providing a renewable source of functional hepatocyte-like cells (HLCs). This study aims to investigate the effect of Fibroblast growth factor (FGF) and Insulin-like Growth Factor (IGF) pre-treatment on the differentiation capacity of Umbilical Cord-Derived Mesenchymal Stem Cells (UC-MSCs) and their potential application in regenerative therapy for liver fibrosis or cirrhosis.</p><p><strong>Methods: </strong>Cell viability was evaluated through MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), crystal violet, and trypan blue assays. For the assessment of differentiation potential, ELISA (Enzyme-Linked Immunosorbent Assay) and Immunocytochemistry of Hepatocyte Growth Factor (HGF) and Epidermal Growth Factor (EGF) were performed. For angiogenesis, an ELISA of Vascular Endothelial Growth Factor (VEGF) was performed. For apoptosis, an ELISA of p53 was performed. Gene expression analysis of differentiation markers, including Cytochrome P450 Family 1 Subfamily A Member 2 (CYP1A2), Cytochrome P450 Family 3 Subfamily A Member 2 (CYP3A2), Hepatocyte Growth Factor (HGF), Epidermal Growth Factor (EGF), Alkaline Phosphatase (ALP), Alpha-Fetoprotein (AFP), and albumin, was also performed. Furthermore, antioxidant enzymes were also measured.</p><p><strong>Results: </strong>UC-MSCs preconditioned with FGF and IGF exhibited significantly enhanced viability and reduced cell death, as confirmed by MTT, crystal violet, and trypan blue assays. ELISA and immunocytochemistry demonstrated marked upregulation of hepatic markers (HGF, EGF), angiogenic factor (VEGF), and reduced expression of the apoptotic marker p53 in the preconditioned groups. The gene expression analysis confirmed superior regenerative potential in the FGF+IGF-treated group. Antioxidative analysis further validated a higher level of antioxidative potential in preconditioned cells.</p><p><strong>Conclusion: </strong>Preconditioned UC-MSCs offer a promising cell-based alternative to liver transplantation by enhancing regeneration, reducing apoptosis, and promoting angiogenesis and antioxidant defense in damaged liver tissue.</p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"14 4","pages":"187-200"},"PeriodicalIF":1.9,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12629968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145585719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of differentiation potential of ovarian surface epithelial stem cells into Oocyte-like cells between human- and mice-derived cells.","authors":"Amoura M Abou-El-Naga, Mohamed A M Sobh, Mohamed M Fathy, Ahmed M Badawy, Ahmed Hk El-Hashash","doi":"10.62347/RQXG2881","DOIUrl":"10.62347/RQXG2881","url":null,"abstract":"<p><strong>Background: </strong>The ovarian surface epithelium (OSE) stem cells are crucial components of the human ovary and play a significant role in both the reproductive function and ovulatory wound repair. Harnessing these stem cells could provide a novel therapeutic strategy for reproductive disorders.</p><p><strong>Methods: </strong>In this study, we determine and compare the differentiation potential of OSE stem cells into Oocyte-like cells between human and mice-derived OSE stem cells. In addition, we assessed OSE cellular characteristics associated with their stemness and self-renewal abilities and demonstrated their capacity for in vitro differentiation.</p><p><strong>Results: </strong>We found that the ovarian surface epithelium harbored putative stem cells characterized by Alkaline Phosphatase (AP) activity, cell proliferation, expression of mesenchymal lineage surface markers, and pluripotent transcriptional markers. Interestingly, human-derived OSE stem cells exhibited increased AP activity and cell proliferation compared to mouse OSE stem cells, suggesting high levels of self-renewal and differentiation potential. Moreover, our evaluation of the in vitro differentiation potential into Oocyte-like cells for human or mouse OSE stem cells demonstrated an enhanced oogenesis potential for human OSE stem cells compared to mouse OSE cells, as evidenced by the analysis of germ cell marker expression and the production of Oocyte-like cells.</p><p><strong>Conclusion: </strong>Our data highlighted the difference in the characterization and differentiation potential into Oocyte-like cells between human-derived OSE stem cells and mouse-derived OSE stem cells and lay a foundation for a future establishment of stem cell line with implications for reproductive cell therapy. In the realm of reproductive medicine, infertile patients with nonfunctional ovaries represent a significant area of interest, and any potential to regenerate their ovaries would hold great importance.</p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"14 4","pages":"170-186"},"PeriodicalIF":1.9,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12629973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145585896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovative approaches in neural stem cell therapy: a comprehensive review of mechanisms and applications.","authors":"Nicholas Panin, Luis Torres, Yug Patel, Alana Michelson, Amanda Hung, Ahmed H El-Hashash","doi":"10.62347/GZVM7194","DOIUrl":"10.62347/GZVM7194","url":null,"abstract":"<p><p>Stem cell therapy is revolutionizing the treatment of neurological disorders, offering innovative approaches for regeneration and repair. This paper explores five distinct mechanisms of stem cell therapy, focusing on their applications and therapeutic potential. Neural stem cells (NSCs) combined with pharmacological agents, such as FTY720, enhance remyelination and neural repair in multiple sclerosis (MS) and spinal cord injuries (SCI). Induced pluripotent stem cells (iPSCs) provide a personalized approach by enabling the generation of patient-specific NSCs for treating conditions like Parkinson's Disease (PD). Gene-editing technologies, such as CRISPR-Cas9, expand the scope of NSC applications by facilitating precise interventions for genetic disorders like SMARD1. Neurotrophic factors derived from NSCs present a cell-free alternative to promote neuronal survival and repair in diseases such as Parkinson's and Huntington's disease. Additionally, NSC-derived extracellular vesicle therapies, such as intranasal delivery methods for AD treatment, offer non-invasive approaches to reduce neuroinflammation and enhance cognitive recovery. While these mechanisms demonstrate remarkable therapeutic potential, challenges such as cost, scalability, and safety remain. This review provides a comprehensive analysis of these mechanisms, highlighting their contributions to the future of regenerative medicine and personalized therapeutic strategies.</p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"14 4","pages":"230-243"},"PeriodicalIF":1.9,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12629974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145585646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosome-rich mesenchymal stem cell secretome improves strength in patients with amyotrophic lateral sclerosis, Kennedy disease, congenital myasthenic syndrome and Lewy body dementia.","authors":"Chadwick C Prodromos, Ruby Del Villar, Max Y Jin, Alaa Abd-Elsayed, Kenneth Candido","doi":"10.62347/FTXA8845","DOIUrl":"10.62347/FTXA8845","url":null,"abstract":"<p><strong>Aim: </strong>Amyotrophic lateral sclerosis (ALS), Lewy Body dementia (LBD), Kennedy disease (KD), and Congenital Myasthenic Syndrome (CMS) are progressive motor disorders for which no disease modifying treatment exists. ALS and LBD are uniformly, and often rapidly, fatal. No treatment of any kind has ever resulted in actual improvement for ALS patients; the best that has been achieved is minor slowing of their progression. Forty-one preclinical studies of intra-nasal instillation of mesenchymal stem cell exosomes have, however, demonstrated complete safety and efficacy for models of a variety of neurocognitive and motor disorders. We hypothesized that intranasal exosomes treatment in humans would be completely safe and also effective for the treatment of motor disorders such as ALS, LBD, KD and CMS.</p><p><strong>Methods: </strong>18 patients with ALS, Kennedy Disease, Congenital Myasthenic Syndrome, or Lewy Body Dementia had 32 AlloEx Exosome^® treatments to assess safety, attenuation of disease, and increase in strength and motor function. The study was conducted under the clinical trial NCT07105371 found at clinicaltrials.gov/study/NCT07105371.</p><p><strong>Results: </strong>There were no adverse events of any kind reported among these treatments. All patients, except for one, achieved some degree of clinical and strength improvement; the longest improvement was recorded at the 6-month follow-up.</p><p><strong>Conclusion: </strong>Intranasally-instilled AlloEx Exosomes^® are completely safe, attenuate progression, and improve strength in ALS, Kennedy Disease, CMS, and LBD.</p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"14 4","pages":"217-229"},"PeriodicalIF":1.9,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12629969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145585661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of key immune genes in mesenchymal stem cells in a 3D environment.","authors":"Haojiang Li, Jianfei Gao, Ren Zhang, Jie Liu, Haiquan Tian, Yujia Xin, Xiaoliang Song, Xiangyi Li, Yuewen He","doi":"10.62347/AMKH1816","DOIUrl":"10.62347/AMKH1816","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study was to identify the different immune-related genes (DIRGs) of mesenchymal stem cells (MSCs) in three-dimensional (3D) vs. two-dimensional (3D) environment.</p><p><strong>Materials and methods: </strong>The gene expression dataset GSE52896 was downloaded from the Gene Expression Omnibus (GEO) database. We obtained immune-related genes from the ImmPort database. The array was processed with the R language to obtain differentially expressed genes (DEGs). A protein-protein interaction (PPI) network was constructed with the STRING database and analyzed with Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis data were performed with DAVID (https://davidbioinformatics.nih.gov/). We constructed a least absolute shrinkage and selection operator (LASSO) regression model and multiple support vector machine - recursive feature elimination (mSVM-RFE) model to identify the key DIRGs in cells growing in 3D culture. The performance of the key genes was validated in the GSE58919 dataset. Western blot analysis was performed to verify the expression of one key gene, Cysteine and Glycine Rich Protein 1 (CSRP1). Key immune-related genes were identified using CIBERSORT (https://cibersortx.stanford.edu/).</p><p><strong>Results: </strong>A total of 446 DEGs were screened under two different culture conditions (2D and 3D), and 65 DEGs were identified. GO analysis revealed changes in inflammatory response, extracellular region, and protein binding. KEGG enrichment analysis showed that the DEGs were enriched in pathways involved in cytokine-cytokine receptor interactions, viral protein interactions with cytokines and cytokine receptors and the TNF signaling pathway. Seven key genes were obtained from the intersection of the outputs of the LASSO and mSVM-RFE algorithms. The expression of the seven key genes was verified in the GSE52896 dataset. Western blot (WB) confirmed the alteration of CSRP1 expression under different culture conditions.</p><p><strong>Conclusion: </strong>Stem cells showed significant changes in immune response gene expression under 3D culture conditions. CSRP1 plays essential roles in MSC immunomodulation.</p>","PeriodicalId":7657,"journal":{"name":"American journal of stem cells","volume":"14 4","pages":"261-276"},"PeriodicalIF":1.9,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12629972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145585955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}