{"title":"Astragaloside IV Treats Parkinson's Disease by Regulating the Proliferation and Differentiation of NSCs through the SHH-Nurr1 Pathway.","authors":"Zicong Wu,Jianing Zhang,Han Gao,Wentao Li","doi":"10.1155/2024/2792909","DOIUrl":"https://doi.org/10.1155/2024/2792909","url":null,"abstract":"Recently, there has been a surge of interest in enhancing the differentiation of neural stem cells (NSCs) and supplementing dopamine neurons as a potential treatment for Parkinson's disease, the second most prevalent neurodegenerative disorder. Two factors, sonic hedgehog (SHH) and nuclear receptor-related 1 protein (Nurr1), have been identified as influential in NSCs differentiation. Additionally, Astragaloside IV (AS-IV), an active compound derived from Astragalus, has also been discovered to impact NSCs differentiation. To assess the effects of AS-IV on cell activity, CCK-8 and flow cytometry techniques were employed. Meanwhile, western blotting, immunofluorescence, and real-time PCR were utilized to detect protein expression both in vivo and in vitro. Furthermore, siRNA assay was used to verify the association between SHH and Nurr1 and to investigate whether AS-IV exerts its effects through this pathway. The experimental findings revealed that AS-IV enhances cell activity and promotes the expression of differentiation proteins related to NSCs. Furthermore, the relationship between the SHH-Nurr1 pathway was confirmed, demonstrating that AS-IV induces NSCs differentiation via this pathway. Consequently, SHH, acting as the upstream signaling pathway of Nurr1, influences its expression, while AS-IV regulates the proliferation and differentiation of NSCs by modulating the SHH-Nurr1 pathway.","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"57 1","pages":"2792909"},"PeriodicalIF":4.3,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142191535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem Cells InternationalPub Date : 2024-08-29eCollection Date: 2024-01-01DOI: 10.1155/2024/5789593
Miaomiao Dai, Weisheng Hong, Yi Ouyang
{"title":"Identification and Validation of Hub Genes and Construction of miRNA-Gene and Transcription Factor-Gene Networks in Adipogenesis of Mesenchymal Stem Cells.","authors":"Miaomiao Dai, Weisheng Hong, Yi Ouyang","doi":"10.1155/2024/5789593","DOIUrl":"10.1155/2024/5789593","url":null,"abstract":"<p><strong>Background: </strong>Adipogenic differentiation stands as a crucial pathway in the range of differentiation options for mesenchymal stem cells (MSCs), carrying significant importance in the fields of regenerative medicine and the treatment of conditions such as obesity and osteoporosis. However, the exact mechanisms that control the adipogenic differentiation of MSCs are not yet fully understood.</p><p><strong>Materials and methods: </strong>We procured datasets, namely GSE36923, GSE80614, GSE107789, and GSE113253, from the Gene Expression Omnibus database. These datasets enabled us to perform a systematic analysis, including the identification of differentially expressed genes (DEGs) pre- and postadipogenic differentiation in MSCs. Subsequently, we conducted an exhaustive analysis of DEGs common to all four datasets. To gain further insights, we subjected these overlapped DEGs to comprehensive gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Following the construction of protein-protein interaction (PPI) networks, we meticulously identified a cohort of hub genes pivotal to the adipogenic differentiation process and validated them using real-time quantitative polymerase chain reaction. Subsequently, we ventured into the construction of miRNA-gene and TF-gene interaction networks.</p><p><strong>Results: </strong>Our rigorous analysis revealed a total of 18 upregulated DEGs and 12 downregulated DEGs that consistently appeared across all four datasets. Notably, the peroxisome proliferator-activated receptor signaling pathway, regulation of lipolysis in adipocytes, and the adipocytokine signaling pathway emerged as the top-ranking pathways significantly implicated in the regulation of these DEGs. Subsequent to the construction of the PPI network, we identified and validated 10 key node genes, namely IL6, FABP4, ADIPOQ, LPL, PLIN1, RBP4, ACACB, NT5E, KRT19, and G0S2. Our endeavor to construct miRNA-gene interaction networks led to the discovery of the top 10 pivotal miRNAs, including hsa-mir-27a-3p, hsa-let-7b-5p, hsa-mir-1-3p, hsa-mir-124-3p, hsa-mir-155-5p, hsa-mir-16-5p, hsa-mir-101-3p, hsa-mir-21-3p, hsa-mir-146a-5p, and hsa-mir-148b-3p. Furthermore, the construction of TF-gene interaction networks revealed the top 10 critical TFs: ZNF501, ZNF512, YY1, EZH2, ZFP37, ZNF2, SOX13, MXD3, ELF3, and TFDP1.</p><p><strong>Conclusions: </strong>In summary, our comprehensive study has successfully unraveled the pivotal hub genes that govern the adipogenesis of MSCs. Moreover, the meticulously constructed miRNA-gene and TF-gene interaction networks are poised to significantly augment our comprehension of the intricacies underlying MSC adipogenic differentiation, thus providing a robust foundation for future advances in regenerative biology.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2024 ","pages":"5789593"},"PeriodicalIF":3.8,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dental Stem Cell-Derived Exosomes: A Review of Their Isolation, Classification, Functions, and Mechanisms.","authors":"Xiner Ning, Rui Liu, Yingying Huang, Zhilong Huang, Haodi Li, Qiqi Li, Zengyan Sheng, Junjie Wu","doi":"10.1155/2024/2187392","DOIUrl":"10.1155/2024/2187392","url":null,"abstract":"<p><p>The scientific field concerned with the study of regeneration has developed rapidly in recent years. Stem cell therapy is a highly promising therapeutic modality for repairing tissue defects; however, several limitations exist, such as cytotoxicity, potential immune rejection, and ethical issues. Exosomes secreted by stem cells are cell-specific secreted vesicles that play a regulatory role in many biological functions in the human body; they not only have a series of functional roles of stem cells and exert the expected therapeutic effects, but they can also overcome the mass limitations of stem cells and are thus considered in the research as an alternative treatment strategy for stem cells. Since dental stem cell-derived exosomes (DSC-Exos) are easy to acquire and present modulating effects in several fields, including neurovascular regeneration and craniofacial soft and hard tissue regeneration processes, they are served as an emerging cell-free therapeutic strategy in various systematic diseases. There is a growing body of research on various types of DSC-Exos; however, they lack systematic elaboration and tabular summarization. Therefore, this review presents the isolation, characterization, and phenotypes of DSC-Exos and focuses on their current status of functions and mechanisms, as well as the multiple challenges prior to clinical applications.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2024 ","pages":"2187392"},"PeriodicalIF":3.8,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11343633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem Cells InternationalPub Date : 2024-08-12eCollection Date: 2024-01-01DOI: 10.1155/2024/4095268
Zesong Chen, Chen Yang, Jiang Ji, Miao Chen, Bing Han
{"title":"Umbilical Cord Blood-Derived Cells Can Reconstruct Hematopoiesis in an Aplastic Anemia Animal Model.","authors":"Zesong Chen, Chen Yang, Jiang Ji, Miao Chen, Bing Han","doi":"10.1155/2024/4095268","DOIUrl":"10.1155/2024/4095268","url":null,"abstract":"<p><strong>Objectives: </strong>To explore the efficacy and the mechanism of the umbilical cord-derived cells combined with cyclosporine A (CsA) in treating aplastic anemia (AA) in mice.</p><p><strong>Methods: </strong>Immune-mediated AA model mice were treated with CsA + UC mesenchymal stem cells (UC-MSC), CsA + umbilical cord blood regulatory T cells (UCB-T<sub>reg</sub>), UC-MSC, UCB-T<sub>reg</sub>, CsA alone, or blank control, respectively (<i>n</i> = 9 mice/group). CsA and the cell infusion was administered on d0. Routine peripheral blood testing was performed once weekly; bone marrow colony culture, bone marrow cell flow cytometry, peripheral blood T cell subsets, and serum inflammatory cytokines tests were performed on d14. Transcriptome sequencing was performed for cells from CsA + UC-MSC, CsA + UCB-T<sub>reg</sub>, and CsA groups to detect the possible related genes. Gene function cluster and signal pathway enrichment analysis were also performed.</p><p><strong>Results: </strong>Blank control mice died due to pancytopenia within 21 days, whereas mice in other groups survived for >28 days. On d14, the CsA + UC-MSC and CsA + UCB-T<sub>reg</sub> groups had higher white blood cell (WBC) counts than the other groups (<i>p</i> < 0.05), along with higher burst-forming unit (BFU) and colony-forming unit-granulocyte, macrophage (CFU-GM) counts (<i>p</i> < 0.01). The CsA + UC-MSC group had the highest BFU count (<i>p</i> < 0.01). The CsA + UC-MSC and CsA + UCB-T<sub>reg</sub> groups exhibited the highest bone marrow CD34<sup>+</sup> cell proportion (9.68% ± 1.35% and 8.17% ± 0.53%, respectively; <i>p</i> < 0.01). Tumor necrosis factor (TNF)-<i>α</i> and interleukin (IL)-2 levels in the CsA + UC-MSC group (<i>p</i> < 0.05) and TNF-<i>α</i>, interleukin-2, and interferon (INF)-<i>γ</i> levels in the CsA + UC-T<sub>reg</sub> group (<i>p</i> < 0.01) were lower than those in the CsA group. Compared with CsA treatment, CsA + UC-MSC significantly downregulated the histone methylation pathway (<i>p</i> < 0.05), whereas CsA + UCB-T<sub>reg</sub> significantly upregulated energy metabolism processes (<i>p</i> < 0.05). Treatment with CsA + UC-MSC upregulated superoxide dismutase activity compared with CsA + UCB-T<sub>reg</sub> treatment.</p><p><strong>Conclusions: </strong>Adding UC-MSC or UCB-T<sub>reg</sub> to CsA markedly enhanced the reconstruction of hematopoiesis in AA mice, with UC-MSC eliciting greater efficiency than UCB-T<sub>reg</sub>. Accordingly, the addition of these cells could further improve immune abnormalities.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2024 ","pages":"4095268"},"PeriodicalIF":3.8,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11333133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142005264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem Cells InternationalPub Date : 2024-08-08eCollection Date: 2024-01-01DOI: 10.1155/2024/9999155
Jared Becerril-Rico, Julian Grandvallet-Contreras, M Patricia Ruíz-León, Sebastián Dorantes-Cano, Lizbeth Ramírez-Vidal, José M Tinajero-Rodríguez, Elizabeth Ortiz-Sánchez
{"title":"Circulating Gastric Cancer Stem Cells as Blood Screening and Prognosis Factor in Gastric Cancer.","authors":"Jared Becerril-Rico, Julian Grandvallet-Contreras, M Patricia Ruíz-León, Sebastián Dorantes-Cano, Lizbeth Ramírez-Vidal, José M Tinajero-Rodríguez, Elizabeth Ortiz-Sánchez","doi":"10.1155/2024/9999155","DOIUrl":"10.1155/2024/9999155","url":null,"abstract":"<p><p>Gastric cancer (GC) is the fourth leading cause of cancer-related death, associated with late diagnosis and treatment resistance. Currently, screening tests for GC are not cost-effective or have low accuracy. Previously, we described an extended phenotype of gastric cancer stem cells (GCSCs; CD24<sup>+</sup>CD44<sup>+</sup>CD54<sup>+</sup>EpCAM<sup>+</sup>) that is associated with metastasis and tumor stage in GC patients. The goal of the current research is to evaluate the presence of these GCSCs in the peripheral blood of GC patients and healthy volunteers. A total of 73 blood samples were collected from 32 GC patients and 41 healthy volunteers. After peripheral blood mononuclear cell (PBMC) extraction, multiparametric flow cytometry was performed looking for GCSCs. Using clustering data through artificial intelligence (AI), we defined high/low levels of circulating GCSCs (cGCSCs) and proceeded to evaluate its association with clinical and prognostic variables. Finally, a diagnostic test analysis was performed evaluating patients and healthy volunteers. We found that cGCSCs are present in most GC patients with a mean concentration of 0.48%. The AI clustering showed two groups with different cGCSC levels and clinical characteristics. Through statistical analysis, we confirmed the association between cGCSC levels and lymph node metastasis, distant metastasis, and overall survival. The diagnostic test analysis showed sensibility, specificity, and area under the curve (AUC) of 83%, 95%, and 0.911, respectively. Our results suggest that the assessment of cGCSCs CD24<sup>+</sup>CD44<sup>+</sup>CD54<sup>+</sup>EpCAM<sup>+</sup> could be a potential noninvasive test, with prognostic value, as well as highly sensitive and specific for screening or diagnosis of GC; however, a larger scale study will be necessary to confirm this.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2024 ","pages":"9999155"},"PeriodicalIF":3.8,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11326876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem Cells InternationalPub Date : 2024-07-30eCollection Date: 2024-01-01DOI: 10.1155/2024/2934308
Marielly Reis Resende Sousa, Amandda Évelin Silva-Carvalho, Maurício Gonçalves da Costa Sousa, Danilo César Mota Martins, Emãnuella Melgaço Garcez, Luma Dayane de Carvalho Filiú Braga, Juliana Lott de Carvalho, Tanise Vendruscolo Dalmolin, Taia Maria Berto Rezende, Felipe Saldanha-Araujo
{"title":"IFN-<i>γ</i>-Licensed Mesenchymal Stem Cells Are More Susceptible to Death when Exposed to Quorum-Sensing Signal Molecule OdDHL and Less Effective in Inhibiting the Growth of <i>Pseudomonas aeruginosa</i>.","authors":"Marielly Reis Resende Sousa, Amandda Évelin Silva-Carvalho, Maurício Gonçalves da Costa Sousa, Danilo César Mota Martins, Emãnuella Melgaço Garcez, Luma Dayane de Carvalho Filiú Braga, Juliana Lott de Carvalho, Tanise Vendruscolo Dalmolin, Taia Maria Berto Rezende, Felipe Saldanha-Araujo","doi":"10.1155/2024/2934308","DOIUrl":"10.1155/2024/2934308","url":null,"abstract":"<p><p>Currently, a series of licensing strategies has been investigated to enhance the functional properties of mesenchymal stem cells (MSCs). Licensing with IFN-<i>γ</i> is one of the most investigated strategies for enhancing the immunosuppressive potential of such cells. However, it is not yet known whether this licensing strategy could interfere with the ability of MSCs to control bacterial growth, which may be relevant considering their clinical potential. In this study, we compared the antimicrobial potential of IFN-<i>γ</i>-licensed and unlicensed MSCs by exposing them to <i>Pseudomonas aeruginosa</i> and its quorum-sensing inducer molecule OdDHL. Our data show that-when challenged with OdDHL-IFN-<i>γ</i>-licensed and unlicensed MSCs present increased levels of the antimicrobial <i>HAMP</i> transcript, but that only IFN-<i>γ</i>-licensed MSCs undergo modulation of <i>CASP1</i> and <i>BCL2</i>, entering apoptosis. Furthermore, we demonstrate that only IFN-<i>γ</i>-licensed MSCs show modulation in genes involved in apoptosis and tend to undergo cell death when cultured with <i>P. aeruginosa</i>. As a consequence, IFN-<i>γ</i>-licensed MSCs showed lower capacity to control bacterial growth, compared to unlicensed MSCs. Taken together, our observations reveal an increased susceptibility to apoptosis of IFN-<i>γ</i>-licensed MSCs, which compromises their potential to control the bacterial growth <i>in vitro</i>. These findings are relevant to the field of cell therapy, considering the potential applicability of MSCs.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2024 ","pages":"2934308"},"PeriodicalIF":3.8,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141898267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem Cells InternationalPub Date : 2024-07-30eCollection Date: 2024-01-01DOI: 10.1155/2024/3100942
Chun-Yi Guan, Dan Zhang, Xue-Cheng Sun, Xu Ma, Hong-Fei Xia
{"title":"hUC-MSC Combined with DHEA Alleviates Ovarian Senescence in Naturally Aging Mice through Enhancing Antioxidant Capacity and Inhibiting Inflammatory Response.","authors":"Chun-Yi Guan, Dan Zhang, Xue-Cheng Sun, Xu Ma, Hong-Fei Xia","doi":"10.1155/2024/3100942","DOIUrl":"10.1155/2024/3100942","url":null,"abstract":"<p><p>The ovary is an important organ for women to maintain reproductive and endocrine functions. Ovarian aging can lead to female reproductive aging, which is a key factor causing rapid aging of the female body. Umbilical cord-derived MSCs (UC-MSCs) play a therapeutic role in various degenerative diseases. Dehydroepiandrosterone (DHEA) is widely used in the treatment of reversing oocyte quality. However, it is unclear whether UC-MSCs combined with DHEA supplementation can improve ovarian senescence in naturally aging mice. To address this question, we studied the influence of the combination of human UC-MSCs (hUC-MSCs) and DHEA on ovarian morphology and function in naturally aging mice. The results showed a significant augmentation in the number of primary follicles, as well as a significant upregulation of estradiol (E2), follicle-stimulating hormone (FSH), and anti-Mullerian hormone (AMH) hormone levels, and a significant increase in survival rate in naturally aging mice treated by hUC-MSCs and DHEA. Moreover, the combination of hUC-MSCs and DHEA significantly reduced the reactive oxygen species (ROS) level and downregulated the expression levels of proinflammatory factors IL-6, IL-18, and TNF-<i>α</i>. Furthermore, the PI3K/AKT/mTOR pathway was inhibited. Conclusively, the combination therapy of hUC-MSC + DHEA contributed to restore ovarian function in aging mice and extend their lifespan by restoring hormone levels and inhibiting inflammatory factors.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2024 ","pages":"3100942"},"PeriodicalIF":3.8,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141898266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem Cells InternationalPub Date : 2024-07-16eCollection Date: 2024-01-01DOI: 10.1155/2024/4654912
Yuting Zeng, Zhenru Wu, Gen Chen, Guoqiang Liu, Bo Zhang, Yongjie Zhou, Menglin Chen, Rong Yao, Yujun Shi
{"title":"Peripheral Injection of hUC-MSCs in the Treatment of Acute Liver Failure: A Pre-Clinical Cohort Study in Rhesus Monkeys.","authors":"Yuting Zeng, Zhenru Wu, Gen Chen, Guoqiang Liu, Bo Zhang, Yongjie Zhou, Menglin Chen, Rong Yao, Yujun Shi","doi":"10.1155/2024/4654912","DOIUrl":"10.1155/2024/4654912","url":null,"abstract":"<p><strong>Background: </strong>Using a toxin-induced lethal acute liver failure (ALF) monkey model, we have recently shown that early peripheral infusion of human umbilical cord mesenchymal stem cells (hUC-MSCs) can alleviate liver damage and improve animal survival by suppressing the activation of circulating monocytes and the subsequent cytokine storm. Here, we explored whether the administration of hUC-MSCs could still improve ALF when the cytokine storm is fully developed.</p><p><strong>Method: </strong>We treated ALF monkeys with peripheral delivery of hUC-MSCs at 48 hr after toxin challenge. Liver indices, histology, imaging, and animal survival were recorded and analyzed.</p><p><strong>Results: </strong>In our cohort study, we conducted and demonstrated that the infusion of hUC-MSCs significantly improved liver histology, effectively controlled inflammatory cytokine storms, and increased survival rates. Additionally, the administration of a higher dose of hUC-MSCs (2 × 10<sup>7</sup>/monkey) yielded superior outcomes compared to a lower dose (1 × 10<sup>7</sup>/monkey).</p><p><strong>Conclusion: </strong>Treatment of hUC-MSCs can significantly improve the pathological and survival outcomes of ALF even when the cytokine storm has been fully developed, indicating a promising clinical solution for ALF.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2024 ","pages":"4654912"},"PeriodicalIF":3.8,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11265939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem Cells InternationalPub Date : 2024-07-09eCollection Date: 2024-01-01DOI: 10.1155/2024/2385568
Bruno Freire Botelho, André Luis Barreira, Marcio Gomes Filippo, Karina Dutra Asensi, Lanuza A P Faccioli, Anna Beatriz Dos Santos Salgado, Elizabeth Figueiredo de Salles, Carlos Eduardo Cruz Marques, Pedro Leme Silva, Regina Coeli Dos Santos Goldenberg, Angelo Maiolino, Bianca Gutfilen, Sergio Augusto Lopes de Souza, Maurilo Leite Junior, Marcelo Marcos Morales
{"title":"Safety and Biodistribution of an Autologous Bone Marrow-Derived Mononuclear Cell Infusion into Renal Arteries in Patients with Focal Segmental Glomerulosclerosis: A Phase 1 Study.","authors":"Bruno Freire Botelho, André Luis Barreira, Marcio Gomes Filippo, Karina Dutra Asensi, Lanuza A P Faccioli, Anna Beatriz Dos Santos Salgado, Elizabeth Figueiredo de Salles, Carlos Eduardo Cruz Marques, Pedro Leme Silva, Regina Coeli Dos Santos Goldenberg, Angelo Maiolino, Bianca Gutfilen, Sergio Augusto Lopes de Souza, Maurilo Leite Junior, Marcelo Marcos Morales","doi":"10.1155/2024/2385568","DOIUrl":"10.1155/2024/2385568","url":null,"abstract":"<p><p>Patients with focal segmental glomerulosclerosis (FSGS) who are refractory to drug treatment may present progressive loss of kidney function, leading to chronic kidney disease stage 5 under dialysis treatment. The safety of systemic administration of bone marrow-derived mononuclear cells (BMDMCs) has been shown in different preclinical models of kidney diseases. However, to date, no study has evaluated the safety and biodistribution of BMDMCs after infusion in renal arteries in patients with FSGS. We used a prospective, non-randomized, single-center longitudinal design to investigate this approach. Five patients with refractory FSGS and an estimated glomerular filtration rate (eGFR) between 20 and 40 ml/min/1.73 m<sup>2</sup> underwent bone marrow aspiration and received an arterial infusion of autologous BMDMCs (5 × 10<sup>7</sup>) for each kidney. In addition, BMDMCs labeled with technetium-99m (<sup>99m</sup>Tc-BMDMCs) were used to assess the biodistribution by scintigraphy. All patients completed the 270-day follow-up protocol with no serious adverse events. A transient increase in creatinine was observed after the cell therapy, with improvement on day 30. <sup>99m</sup>Tc-BMDMCs were detected in both kidneys and counts were higher after 2 hr compared with 24 hr. The arterial infusion of BMDMCs in both kidneys of patients with FSGS was considered safe with stable eGFR at the end of follow-up. This trial is registered with NCT02693366.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2024 ","pages":"2385568"},"PeriodicalIF":3.8,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11251782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}