Stem Cells International最新文献

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Retracted: Effects of Fibulin-5 Gene Silencing on Proliferation and Apoptosis of IgG4-ROD Lacrimal Gland Fibroblasts 撤回:Fibulin-5基因沉默对IgG4-ROD泪腺成纤维细胞增殖和凋亡的影响
IF 4.3 3区 医学
Stem Cells International Pub Date : 2023-12-20 DOI: 10.1155/2023/9856916
Stem Cells International
{"title":"Retracted: Effects of Fibulin-5 Gene Silencing on Proliferation and Apoptosis of IgG4-ROD Lacrimal Gland Fibroblasts","authors":"Stem Cells International","doi":"10.1155/2023/9856916","DOIUrl":"https://doi.org/10.1155/2023/9856916","url":null,"abstract":"<jats:p />","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"76 4","pages":""},"PeriodicalIF":4.3,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138954461","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}
引用次数: 0
Combination Therapy with Platelet-Rich Plasma and Epidermal Neural Crest Stem Cells Increases Treatment Efficacy in Vascular Dementia 富血小板血浆和表皮神经干细胞联合疗法可提高血管性痴呆症的疗效
IF 4.3 3区 医学
Stem Cells International Pub Date : 2023-12-18 DOI: 10.1155/2023/3784843
Somayeh Akbari, Masoud Haghani, Mojtaba Ghobadi, Etrat Hooshmandi, Afshin Borhani Haghighi, Mohammad Saied Salehi, Sareh Pandamooz, Negar Azarpira, Afsoon Afshari, Shahrbanoo Zabihi, Marzieh Nemati, Mahnaz Bayat
{"title":"Combination Therapy with Platelet-Rich Plasma and Epidermal Neural Crest Stem Cells Increases Treatment Efficacy in Vascular Dementia","authors":"Somayeh Akbari, Masoud Haghani, Mojtaba Ghobadi, Etrat Hooshmandi, Afshin Borhani Haghighi, Mohammad Saied Salehi, Sareh Pandamooz, Negar Azarpira, Afsoon Afshari, Shahrbanoo Zabihi, Marzieh Nemati, Mahnaz Bayat","doi":"10.1155/2023/3784843","DOIUrl":"https://doi.org/10.1155/2023/3784843","url":null,"abstract":"This study aimed to evaluate the efficacy and treatment mechanism of platelet-rich plasma (PRP) and neural crest-derived epidermal stem cells (ESCs) in their administration alone and combination in vascular dementia (VaD) model by two-vessel occlusion (2VO). <i>Methods</i>. Sixty-six rats were divided into six groups: the control, sham, 2VO + vehicle, 2VO + PRP, 2VO + ESC, and 2VO + ESC + PRP. The treated groups received 1 million cells on days 4, 14, and 21 with or without 500 <i>µ</i>l PRP (twice a week) after 2VO. The memory performance and anxiety were evaluated by behavioral tests including open field, passive avoidance, and Morris water maze. The basal-synaptic transmission (BST) and long-term potentiation (LTP) were assessed through field-potential recordings of the CA1. The mRNA expression levels of IGF-1, TGF-<i>β</i>1, PSD-95, and GSk-3<i>β</i> were measured in the rat hippocampus by quantitative reverse transcription polymerase chain reaction. <i>Results</i>. The results demonstrated impaired learning, memory, and synaptic plasticity in the 2VO rats, along with a significant decrease in the expression of IGF-1, TGF-<i>β</i>1, PSD-95, and upregulation of GSK-3<i>β</i>. Treatment with ESC alone and ESC + PRP showed similar improvements in spatial memory and LTP induction, with associated upregulation of PSD-95 and downregulation of GSK-3<i>β</i>. However, only the ESC + PRP group showed recovery in BST. Furthermore, combination therapy was more effective than PRP monotherapy for LTP and memory. <i>Conclusions</i>. The transplantation of ESC showed better effects than PRP alone, and combination therapy increased the treatment efficacy with the recovery of BST. This finding may be a clue for the combination therapy of ESC and PRP for VaD.","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"1 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138715553","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}
引用次数: 0
Advances and Challenges in Cancer Stem Cells for Onco-Therapeutics 肿瘤干细胞治疗的进展和挑战
IF 4.3 3区 医学
Stem Cells International Pub Date : 2023-12-06 DOI: 10.1155/2023/8722803
Sulaiman Mohammed Alnasser
{"title":"Advances and Challenges in Cancer Stem Cells for Onco-Therapeutics","authors":"Sulaiman Mohammed Alnasser","doi":"10.1155/2023/8722803","DOIUrl":"https://doi.org/10.1155/2023/8722803","url":null,"abstract":"Six decades have passed since the foundational recognition of the primary properties of the stem cells. Research on stem cells has since remained at the forefront of efforts to combat a spectrum of diseases, most notably cancer. Despite remarkable progress in medical science, a definitive cure for cancer has remained elusive, spurring the pursuit of diverse therapeutic strategies, among which stem cell therapy is a particularly promising avenue. Moreover, the utilization of cancer stem cells as a therapeutic source holds immense potential for addressing intractable diseases. The strategy of targeting cancer stem cells is beset with challenges, including immune rejection and disease relapse. Additionally, the capacity to inadvertently generate cancer stem cells upon transplantation underscores the critical need to eliminate these cells to ensure the efficacy of cell-based therapies. This paper underscores the pivotal role of cancer stem cells in onco-therapeutics and their potential to aid in early cancer diagnosis. With the proliferation of tissue banks and their collection of malignant tissue types, a renewable source of medications to combat cancer is on the horizon. While cancer stem cell-based therapy presents sophisticated and significant challenges, it offers unprecedented opportunities to extend human life. Continued technological advancements in stem cell therapy promise to provide new insights and refine approaches for cancer treatment, ushering in a new era of hope and innovation in the fight against this formidable disease.","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"209 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138541162","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}
引用次数: 0
Human Umbilical Cord Perivascular Cells Prevent Tumor Growth in a Melanoma Tumor-Bearing Mouse Model and Modulate Breast Cancer and Melanoma Cells in a Cell Line-Dependent Manner In Vitro 人脐带血管周围细胞在黑色素瘤荷瘤小鼠模型中阻止肿瘤生长,并在体外以细胞系依赖的方式调节乳腺癌和黑色素瘤细胞
IF 4.3 3区 医学
Stem Cells International Pub Date : 2023-11-30 DOI: 10.1155/2023/5568206
Lianet Lopez, Hannah Shuster-Hyman, Eden Marco, Hasna Khan, Avishai Gasner, Aleksandra Uzelac, Brandon Wyse, Poonam Mander, Mugundhine Sangaralingam, Joseph Fish, Ariel Gorodensky, Samar Mouazz, Amanda Kauffman, Denis Gallagher, Andrée Gauthier-Fisher, Clifford L. Librach
{"title":"Human Umbilical Cord Perivascular Cells Prevent Tumor Growth in a Melanoma Tumor-Bearing Mouse Model and Modulate Breast Cancer and Melanoma Cells in a Cell Line-Dependent Manner In Vitro","authors":"Lianet Lopez, Hannah Shuster-Hyman, Eden Marco, Hasna Khan, Avishai Gasner, Aleksandra Uzelac, Brandon Wyse, Poonam Mander, Mugundhine Sangaralingam, Joseph Fish, Ariel Gorodensky, Samar Mouazz, Amanda Kauffman, Denis Gallagher, Andrée Gauthier-Fisher, Clifford L. Librach","doi":"10.1155/2023/5568206","DOIUrl":"https://doi.org/10.1155/2023/5568206","url":null,"abstract":"First trimester (FTM) and term human umbilical cord perivascular cells are promising mesenchymal stromal cell candidates to mitigate side effects of oncotherapy, but their safety for cancer patients remains to be determined. This study was designed to determine if human umbilical cord perivascular cells modulate tumor growth when injected systemically in a tumor-bearing mouse model. Immunodeficient mice-bearing palpable subcutaneous SK-MEL-28 human melanoma tumors were randomized to receive a tail vein injection of three human umbilical cord perivascular cell lines resuspended in hank’s buffer saline solution (vehicle) or vehicle only, as a control. Fibroblast cells were included as a cell control in some experiments. Tumor size was monitored weekly and weighed at 3-weeks postinjection. Cell fate and tumor cell proliferation, apoptosis, vascularization as well as tumor-associated immune cells were assessed using immunostaining and flow cytometry. Serum tumor necrosis factor alpha and C-reactive protein levels were measured using enzyme-linked immunosorbent assays. Transwell coculture models were used to study the paracrine effects of multiple lines of human umbilical cord cells on human melanoma cell lines as well as breast cancer cell lines. Systemic administration of FTM and term human umbilical cord perivascular cells, but not fibroblast cells, prevented melanoma tumor growth in a tumor-bearing animal model by modulating tumor cell proliferation and systemic inflammatory mechanisms. Cancer cell- and donor-dependent paracrine effects on cancer cell growth were observed <i>in vitro</i>. Our preclinical studies thus suggest that, with regards to its effects on tumor growth, systemic administration of FTM and term human umbilical cord perivascular cells may be a safe cell therapy to address the side effects of cancer.","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"40 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138541156","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}
引用次数: 0
Unveiling Cellular Traits of Osteosarcoma Cancer Stem Cells via Bulk and Single-Cell RNA-Sequencing Analysis 通过大量和单细胞rna测序分析揭示骨肉瘤癌症干细胞的细胞特性
IF 4.3 3区 医学
Stem Cells International Pub Date : 2023-11-22 DOI: 10.1155/2023/2923728
Zhen Zhao, Shun Niu, Zhixiang Yu, Hongtao Zhang, Lizhuo Liang, Kui Xu, Chuan Dong, Hua Long
{"title":"Unveiling Cellular Traits of Osteosarcoma Cancer Stem Cells via Bulk and Single-Cell RNA-Sequencing Analysis","authors":"Zhen Zhao, Shun Niu, Zhixiang Yu, Hongtao Zhang, Lizhuo Liang, Kui Xu, Chuan Dong, Hua Long","doi":"10.1155/2023/2923728","DOIUrl":"https://doi.org/10.1155/2023/2923728","url":null,"abstract":"Osteosarcoma (OS) is a prototypical sarcoma, predominantly affecting adolescents. The hallmark of cancer stem cell (CSC) behavior pervades OS, invariably signifying an unfavorable prognosis. However, the intricacies underlying OS metastasis remain incompletely comprehended. As the frontiers of the scientific investigation push forward, encompassing both bulk sequencing and single-cell sequencing (scRNA), the domain of bioinformatics finds multifaceted utility. In this study, we combined scRNA and bulk sequencing with the clinical metadata to excavate the latent molecular substrates governing metastatic propensities within OS. Our scRNA analysis indicated that cell-stemness-related pathways might play vital roles in OS metastasis. Subsequently, an autonomous reservoir of bulk sequencing data set was subjected to weighted gene co-expression network analysis (WGCNA) to identify 10 gene clusters. After analyzing the clinical data, we were able to identify two hub genes, HDAC2 and HSPA4, which are strongly linked to the cancer cell stemness. Moreover, we performed transwell assays to validate the regulation of metastatic behaviors by miR-1-3p, HDAC2, and HSPA4 in OS cells. Significantly, our study was fortified by immunohistochemistry (IHC) analyses performed on tumor tissues acquired from OS patients, thereby accentuating the clinical import of our experimental endeavor. Notably, we unveiled the suppressive influence of miR-1-3p on both HDAC2 and HSPA4, with miRTarBase substantiating lower expression in tumor tissue relative to the normative cohort. Insights gleaned from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) program (https://ocg.cancer.gov/programs/target) further augmented the clinical significance of the identified hub genes. In conclusion, our findings highlight the significant role of cell junctions in governing OS stemness and metastasis, underscored by the integration of single-cell sequencing and bulk-sequencing analyses. Moreover, our foundational experiments identified three hub molecules closely associated with the metastatic behaviors. Our findings provide novel insights into the clinical treatment and fundamental understanding of OS.","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"73 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138541135","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}
引用次数: 0
Mechanisms and Optimization Strategies of Paracrine Exosomes from Mesenchymal Stem Cells in Ischemic Heart Disease. 缺血性心脏病中间充质干细胞旁分泌外泌体的机制和优化策略。
IF 4.3 3区 医学
Stem Cells International Pub Date : 2023-11-22 eCollection Date: 2023-01-01 DOI: 10.1155/2023/6500831
Xiaorong Yin, Lizhi Lin, Fang Fang, Bin Zhang, Cheng Shen
{"title":"Mechanisms and Optimization Strategies of Paracrine Exosomes from Mesenchymal Stem Cells in Ischemic Heart Disease.","authors":"Xiaorong Yin, Lizhi Lin, Fang Fang, Bin Zhang, Cheng Shen","doi":"10.1155/2023/6500831","DOIUrl":"10.1155/2023/6500831","url":null,"abstract":"<p><p>The morbidity and mortality of myocardial infarction (MI) are increasing worldwide. Mesenchymal stem cells (MSCs) are multipotent stem cells with self-renewal and differentiation capabilities that are essential in tissue healing and regenerative medicine. However, the low implantation and survival rates of transplanted cells hinder the widespread clinical use of stem cells. Exosomes are naturally occurring nanovesicles that are secreted by cells and promote the repair of cardiac function by transporting noncoding RNA and protein. In recent years, MSC-derived exosomes have been promising cell-free treatment tools for improving cardiac function and reversing cardiac remodeling. This review describes the biological properties and therapeutic potential of exosomes and summarizes some engineering approaches for exosomes optimization to enhance the targeting and therapeutic efficacy of exosomes in MI.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2023 ","pages":"6500831"},"PeriodicalIF":4.3,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10686715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138462735","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}
引用次数: 0
Photobiomodulation Can Enhance Stem Cell Viability in Cochlea with Auditory Neuropathy but Does Not Restore Hearing. 光生物调节可增强听神经病变耳蜗干细胞活力,但不能恢复听力。
IF 4.3 3区 医学
Stem Cells International Pub Date : 2023-11-15 eCollection Date: 2023-01-01 DOI: 10.1155/2023/6845571
So-Young Chang, Eunjeong Kim, Nathaniel T Carpena, Jae-Hun Lee, Doo Hee Kim, Min Young Lee
{"title":"Photobiomodulation Can Enhance Stem Cell Viability in Cochlea with Auditory Neuropathy but Does Not Restore Hearing.","authors":"So-Young Chang, Eunjeong Kim, Nathaniel T Carpena, Jae-Hun Lee, Doo Hee Kim, Min Young Lee","doi":"10.1155/2023/6845571","DOIUrl":"https://doi.org/10.1155/2023/6845571","url":null,"abstract":"<p><p>Sensorineural hearing loss is very difficult to treat. Currently, one of the techniques used for hearing rehabilitation is a cochlear implant that can transform sound into electrical signals instead of inner ear hair cells. However, the prognosis remains very poor if sufficient auditory nerve cells are not secured. In this study, the effect of mouse embryonic stem cells (mESC) and photobiomodulation (PBM) combined treatment on auditory function and auditory nerve cells in a secondary neuropathy animal model was investigated. To confirm the engraftment of stem cells in vitro, cochlear explants were treated with kanamycin (KM) to mimic nerve damage and then cocultured with GFP-mESC. GFP-mESCs were observed to have attached and integrated into the explanted samples. An animal model for secondary neurodegeneration was achieved by KM treatment and was treated by a combination therapy of GFP-mESC and NIR-PBM at 8 weeks of KM treatment. Hearing recovery by functional testing using auditory brain stem response (ABR) and eABR was measured as well as morphological changes and epifluorescence analysis were conducted after 2 weeks of combination therapy. KM treatment elevated the hearing threshold at 70-80 dB and even after the combination treatment with GFP-mESC and PBM was applied, the auditory function was not restored. In addition, the stem cells transplanted into cochlea has exponentially increased due to PBM treatment although did not produce any malignancy. This study confirmed that the combined treatment with mESC and PBM could not improve hearing or increase the response of the auditory nerve. Nevertheless, it is noteworthy in this study that the cells are distributed in most cochlear tissues and the proliferation of stem cells was very active in animals irradiated with PBM compared to other groups wherein the stem cells had disappeared immediately after transplantation or existed for only a short period of time.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2023 ","pages":"6845571"},"PeriodicalIF":4.3,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10665102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138462736","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}
引用次数: 0
Umbilical Cord Mesenchymal Stem Cells Overexpressing Heme Oxygenase-1 Promotes Symptoms Recovery in Cystitis Rats by Alleviating Neuroinflammation 过表达血红素加氧酶-1的脐带间充质干细胞通过减轻神经炎症促进膀胱炎大鼠症状恢复
3区 医学
Stem Cells International Pub Date : 2023-11-14 DOI: 10.1155/2023/8887091
Qiongqiong Gao, Zhentao Gao, Minzhi Su, Yong Huang, Chi Zhang, Cuiping Li, Hailun Zhan, Bolong Liu, Xiangfu Zhou
{"title":"Umbilical Cord Mesenchymal Stem Cells Overexpressing Heme Oxygenase-1 Promotes Symptoms Recovery in Cystitis Rats by Alleviating Neuroinflammation","authors":"Qiongqiong Gao, Zhentao Gao, Minzhi Su, Yong Huang, Chi Zhang, Cuiping Li, Hailun Zhan, Bolong Liu, Xiangfu Zhou","doi":"10.1155/2023/8887091","DOIUrl":"https://doi.org/10.1155/2023/8887091","url":null,"abstract":"Interstitial cystitis/bladder pain syndrome (IC/BPS) seriously reduces the patient’s quality of life, yet current therapies only provide partial relief. In the spinal dorsal horn (SDH), neuroinflammation plays a pivotal role in the development of IC. Injection of human umbilical cord mesenchymal stem cells (hUMSCs) to reduce inflammation is an effective strategy, and heme oxygenase-1 (HO-1) exhibits anti-nociceptive effect in neuroinflammatory pain. This study aimed to test the therapeutic effects of hUMSCs overexpressing HO-1 on cyclophosphamide-induced cystitis rat model. Cystitis rats were transplanted with altered cells and then assessed for 3 weeks. A series of behavioral measurements would be trial including suprapubic mechanical allodynia, depressive-like behaviors, micturition frequency, and short-term memory function. Additionally, western blot, immunofluorescence staining, and ELISA kit test for anti-inflammation effect. HUMSCs were capable of being transduced to overexpress HO-1. Injection of hUMSCs overexpressing HO-1 was more effective than hUMSCs alone in alleviating behavioral symptoms in rats. Furthermore, hUMSCs overexpressing HO-1 inhibited the activation of glial and TLR4/p65/NLRP3 pathway, decreased the levels of pro-inflammatory cytokines in the SDH region. Surprisingly, it markedly increased anti-inflammatory cytokine IL-10, reduced MDA content, and protected GSH concentrations in local environment. Our results suggest that injecting hUMSCs overexpressing HO-1 intrathecally can significantly promote functional outcomes in cystitis rats by reducing neuroinflammation, at least, partly through downregulating TLR4/p65/NLRP3 signaling pathway in the SDH region. This cell therapy affords a new strategy for IC/BPS treatment.","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"68 7","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134900627","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}
引用次数: 0
CRISPR/Cas9 Genome Editing in LGMD2A/R1 Patient-Derived Induced Pluripotent Stem and Skeletal Muscle Progenitor Cells CRISPR/Cas9基因组编辑在LGMD2A/R1患者来源的诱导多能干细胞和骨骼肌祖细胞中的应用
3区 医学
Stem Cells International Pub Date : 2023-11-09 DOI: 10.1155/2023/9246825
Lampros Mavrommatis, Abdul Zaben, Urs Kindler, Marie-Cécile Kienitz, Julienne Dietz, Hyun-Woo Jeong, Pierre Böhme, Beate Brand-Saberi, Matthias Vorgerd, Holm Zaehres
{"title":"CRISPR/Cas9 Genome Editing in LGMD2A/R1 Patient-Derived Induced Pluripotent Stem and Skeletal Muscle Progenitor Cells","authors":"Lampros Mavrommatis, Abdul Zaben, Urs Kindler, Marie-Cécile Kienitz, Julienne Dietz, Hyun-Woo Jeong, Pierre Böhme, Beate Brand-Saberi, Matthias Vorgerd, Holm Zaehres","doi":"10.1155/2023/9246825","DOIUrl":"https://doi.org/10.1155/2023/9246825","url":null,"abstract":"Large numbers of Calpain 3 (CAPN3) mutations cause recessive forms of limb-girdle muscular dystrophy (LGMD2A/LGMDR1) with selective atrophy of the proximal limb muscles. We have generated induced pluripotent stem cells (iPSC) from a patient with two mutations in exon 3 and exon 4 at the calpain 3 locus (W130C, 550delA). Two different strategies to rescue these mutations are devised: (i) on the level of LGMD2A-iPSC, we combined CRISPR/Cas9 genome targeting with a FACS and Tet transactivator-based biallelic selection strategy, which resulted in a new functional chimeric exon 3-4 without the two CAPN3 mutations. (ii) On the level of LGMD2A-iPSC-derived CD82+/Pax7+ myogenic progenitor cells, we demonstrate CRISPR/Cas9 mediated rescue of the highly prevalent exon 4 CAPN3 mutation. The first strategy specifically provides isogenic LGMD2A corrected iPSC for disease modelling, and the second strategy can be further elaborated for potential translational approaches.","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":" 6","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135192301","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}
引用次数: 0
Adipose-Derived Mesenchymal Stem Cell Facilitate Hematopoietic Stem Cell Proliferation via the Jagged-1/Notch-1/Hes Signaling Pathway 脂肪源性间充质干细胞通过Jagged-1/Notch-1/Hes信号通路促进造血干细胞增殖
3区 医学
Stem Cells International Pub Date : 2023-11-09 DOI: 10.1155/2023/1068405
Hongbo Wang, Xiaojuan Bi, Rongyao Zhang, Hailong Yuan, Jianli Xu, Kaile Zhang, Songqing Qi, Xue Zhang, Ming Jiang
{"title":"Adipose-Derived Mesenchymal Stem Cell Facilitate Hematopoietic Stem Cell Proliferation via the Jagged-1/Notch-1/Hes Signaling Pathway","authors":"Hongbo Wang, Xiaojuan Bi, Rongyao Zhang, Hailong Yuan, Jianli Xu, Kaile Zhang, Songqing Qi, Xue Zhang, Ming Jiang","doi":"10.1155/2023/1068405","DOIUrl":"https://doi.org/10.1155/2023/1068405","url":null,"abstract":"Background. Poor graft function (PGF) is a life-threatening complication following hematopoietic stem cell transplantation (HSCT). Current therapies, such as CD34+ cell infusion, have shown limited effectiveness. Conversely, mesenchymal stem cells (MSCs) show potential in addressing PGF. Adipose-derived mesenchymal stem cells (ADSCs) effectively support long-term hematopoietic stem cell proliferation. Therefore, this study aimed to investigate the mechanisms underlying the long-term hematopoietic support provided by ADSCs. Methods. ADSCs were isolated from mice and subsequently identified. In vitro experiments involved coculturing ADSCs as feeders with Lin-Sca-1+c-kit+ (LSK) cells from mice for 2 and 5 weeks. The number of LSK cells was quantified after coculture. Scanning electron microscopy was utilized to observe the interaction between ADSCs and LSK cells. Hes-1 expression was assessed using western blot and real-time quantitative PCR. An γ-secretase inhibitor (GSI) was used to confirm the involvement of the Jagged-1/Notch-1/Hes-1 pathway in LSK cell expansion. Additionally, Jagged-1 was knocked down in ADSCs to demonstrate its significance in ADSC-mediated hematopoietic support. In vivo experiments were conducted to study the hematopoietic support provided by ADSCs through the infusion of LSK, LSK + fibroblasts, and LSK + ADSCs, respectively. Mouse survival, platelet count, leukocyte count, and hemoglobin levels were monitored. Results. ADSCs showed high-Jagged-1 expression and promoted LSK cell proliferation. There was a direct interaction between ADSCs and LSK cells. After coculture, Hes-1 expression increased in LSK cells. Moreover, GSI-reduced LSK cell proliferation and Hes-1 expression. Knockdown of Jagged-1 attenuated ADSCs-mediated promotion of LSK cell proliferation. Furthermore, ADSCs facilitated hematopoietic recovery and promoted the survival of NOD/SCID mice. Conclusion. The hematopoietic support provided by ADSCs both in vivo and in vitro may be mediated, at least in part, through the Jagged-1/Notch-1 signaling pathway. These findings provide valuable insights into the mechanisms underlying ADSCs-mediated hematopoietic support and may have implications for improving the treatment of PGF following HSCT.","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":" 32","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135241000","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}
引用次数: 0
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