International journal of stem cells最新文献

{"title":"Low-Intensity Pulsed Ultrasound Promotes BMP9 Induced Osteoblastic Differentiation in Rat Dedifferentiated Fat Cells.","authors":"Fumiaki Setoguchi, Kotaro Sena, Kazuyuki Noguchi","doi":"10.15283/ijsc23027","DOIUrl":"10.15283/ijsc23027","url":null,"abstract":"<p><p>Dedifferentiated fat cells (DFATs) isolated from mature adipocytes have a multilineage differentiation capacity similar to mesenchymal stem cells and are considered as promising source of cells for tissue engineering. Bone morphogenetic protein 9 (BMP9) and low-intensity pulsed ultrasound (LIPUS) have been reported to stimulate bone formation both <i>in vitro</i> and <i>in vivo</i>. However, the combined effect of BMP9 and LIPUS on osteoblastic differentiation of DFATs has not been studied. After preparing DFATs from mature adipose tissue from rats, DFATs were treated with different doses of BMP9 and/or LIPUS. The effects on osteoblastic differentiation were assessed by changes in alkaline phosphatase (ALP) activity, mineralization/calcium deposition, and expression of bone related genes; Runx2, osterix, osteopontin. No significant differences for ALP activity, mineralization deposition, as well as expression for bone related genes were observed by LIPUS treatment alone while treatment with BMP9 induced osteoblastic differentiation of DFATs in a dose dependent manner. Further, co-treatment with BMP9 and LIPUS significantly increased osteoblastic differentiation of DFATs compared to those treated with BMP9 alone. In addition, upregulation for BMP9-receptor genes was observed by LIPUS treatment. Indomethacin, an inhibitor of prostaglandin synthesis, significantly inhibited the synergistic effect of BMP9 and LIPUS co-stimulation on osteoblastic differentiation of DFATs. LIPUS promotes BMP9 induced osteoblastic differentiation of DFATs <i>in vitro</i> and prostaglandins may be involved in this mechanism.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"406-414"},"PeriodicalIF":2.3,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10686803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9690160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parathyroid Hormone-Related Protein Promotes the Proliferation of Patient-Derived Glioblastoma Stem Cells via Activating cAMP/PKA Signaling Pathway.","authors":"Zhenyu Guo,&nbsp;Tingqin Huang,&nbsp;Yingfei Liu,&nbsp;Chongxiao Liu","doi":"10.15283/ijsc22097","DOIUrl":"https://doi.org/10.15283/ijsc22097","url":null,"abstract":"<p><strong>Background and objectives: </strong>Glioblastoma (GBM) is an aggressive primary brain tumor characterized by its heterogeneity and high recurrence and lethality rates. Glioblastoma stem cells (GSCs) play a crucial role in therapy resistance and tumor recurrence. Therefore, targeting GSCs is a key objective in developing effective treatments for GBM. The role of Parathyroid hormone-related peptide (PTHrP) in GBM and its impact on GSCs remains unclear. This study aimed to investigate the effect of PTHrP on GSCs and its potential as a therapeutic target for GBM.</p><p><strong>Methods and results: </strong>Using the Cancer Genome Atlas (TCGA) database, we found higher expression of PTHrP in GBM, which correlated inversely with survival. GSCs were established from three human GBM samples obtained after surgical resection. Exposure to recombinant human PTHrP protein (rPTHrP) at different concentrations significantly enhanced GSCs viability. Knockdown of PTHrP using target-specific siRNA (siPTHrP) inhibited tumorsphere formation and reduced the number of BrdU-positive cells. In an orthotopic xenograft mouse model, suppression of PTHrP expression led to significant inhibition of tumor growth. The addition of rPTHrP in the growth medium counteracted the antiproliferative effect of siPTHrP. Further investigation revealed that PTHrP increased cAMP concentration and activated the PKA signaling pathway. Treatment with forskolin, an adenylyl cyclase activator, nullified the antiproliferative effect of siPTHrP.</p><p><strong>Conclusions: </strong>Our findings demonstrate that PTHrP promotes the proliferation of patient-derived GSCs by activating the cAMP/PKA signaling pathway. These results uncover a novel role for PTHrP and suggest its potential as a therapeutic target for GBM treatment.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 3","pages":"315-325"},"PeriodicalIF":2.3,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7f/9f/ijsc-16-3-315.PMC10465338.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10124843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Applications of Bioinspired Platforms for Enhancing Immunomodulatory Function of Mesenchymal Stromal Cells.","authors":"Ok-Hyeon Kim,&nbsp;Tae Jin Jeon,&nbsp;Young In So,&nbsp;Yong Kyoo Shin,&nbsp;Hyun Jung Lee","doi":"10.15283/ijsc22211","DOIUrl":"https://doi.org/10.15283/ijsc22211","url":null,"abstract":"<p><p>Mesenchymal stromal cells (MSCs) have attracted scientific and medical interest due to their self-renewing properties, pluripotency, and paracrine function. However, one of the main limitations to the clinical application of MSCs is their loss of efficacy after transplantation <i>in vivo</i>. Various bioengineering technologies to provide stem cell niche-like conditions have the potential to overcome this limitation. Here, focusing on the stem cell niche microenvironment, studies to maximize the immunomodulatory potential of MSCs by controlling biomechanical stimuli, including shear stress, hydrostatic pressure, stretch, and biophysical cues, such as extracellular matrix mimetic substrates, are discussed. The application of biomechanical forces or biophysical cues to the stem cell microenvironment will be beneficial for enhancing the immunomodulatory function of MSCs during cultivation and overcoming the current limitations of MSC therapy.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 3","pages":"251-259"},"PeriodicalIF":2.3,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a4/11/ijsc-16-3-251.PMC10465339.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10124844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dissection of Cellular Communication between Human Primary Osteoblasts and Bone Marrow Mesenchymal Stem Cells in Osteoarthritis at Single-Cell Resolution.","authors":"Ying Liu, Yan Chen, Xiao-Hua Li, Chong Cao, Hui-Xi Zhang, Cui Zhou, Yu Chen, Yun Gong, Jun-Xiao Yang, Liang Cheng, Xiang-Ding Chen, Hui Shen, Hong-Mei Xiao, Li-Jun Tan, Hong-Wen Deng","doi":"10.15283/ijsc22101","DOIUrl":"10.15283/ijsc22101","url":null,"abstract":"<p><strong>Background and objectives: </strong>Osteoblasts are derived from bone marrow mesenchymal stem cells (BMMSCs) and play important role in bone remodeling. While our previous studies have investigated the cell subtypes and heterogeneity in osteoblasts and BMMSCs separately, cell-to-cell communications between osteoblasts and BMMSCs <i>in vivo</i> in humans have not been characterized. The aim of this study was to investigate the cellular communication between human primary osteoblasts and bone marrow mesenchymal stem cells.</p><p><strong>Methods and results: </strong>To investigate the cell-to-cell communications between osteoblasts and BMMSCs and identify new cell subtypes, we performed a systematic integration analysis with our single-cell RNA sequencing (scRNA-seq) transcriptomes data from BMMSCs and osteoblasts. We successfully identified a novel preosteoblasts subtype which highly expressed ATF3, CCL2, CXCL2 and IRF1. Biological functional annotations of the transcriptomes suggested that the novel preosteoblasts subtype may inhibit osteoblasts differentiation, maintain cells to a less differentiated status and recruit osteoclasts. Ligand-receptor interaction analysis showed strong interaction between mature osteoblasts and BMMSCs. Meanwhile, we found <i>FZD1</i> was highly expressed in BMMSCs of osteogenic differentiation direction. WIF1 and <i>SFRP4</i>, which were highly expressed in mature osteoblasts were reported to inhibit osteogenic differentiation. We speculated that WIF1 and sFRP4 expressed in mature osteoblasts inhibited the binding of FZD1 to Wnt ligand in BMMSCs, thereby further inhibiting osteogenic differentiation of BMMSCs.</p><p><strong>Conclusions: </strong>Our study provided a more systematic and comprehensive understanding of the heterogeneity of osteogenic cells. At the single cell level, this study provided insights into the cell-to-cell communications between BMMSCs and osteoblasts and mature osteoblasts may mediate negative feedback regulation of osteogenesis process.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 3","pages":"342-355"},"PeriodicalIF":2.5,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3a/76/ijsc-16-3-342.PMC10465330.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10124281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wedelolactone Promotes the Chondrogenic Differentiation of Mesenchymal Stem Cells by Suppressing EZH2.","authors":"Wei Qin,&nbsp;Lin Yang,&nbsp;Xiaotong Chen,&nbsp;Shanyu Ye,&nbsp;Aijun Liu,&nbsp;Dongfeng Chen,&nbsp;Kunhua Hu","doi":"10.15283/ijsc22046","DOIUrl":"https://doi.org/10.15283/ijsc22046","url":null,"abstract":"<p><strong>Background and objectives: </strong>Osteoarthritis (OA) is a degenerative disease that leads to the progressive destruction of articular cartilage. Current clinical therapeutic strategies are moderately effective at relieving OA-associated pain but cannot induce chondrocyte differentiation or achieve cartilage regeneration. We investigated the ability of wedelolactone, a biologically active natural product that occurs in Eclipta alba (false daisy), to promote chondrogenic differentiation.</p><p><strong>Methods and results: </strong>Real-time reverse transcription-polymerase chain reaction, immunohistochemical staining, and immunofluorescence staining assays were used to evaluate the effects of wedelolactone on the chondrogenic differentiation of mesenchymal stem cells (MSCs). RNA sequencing, microRNA (miRNA) sequencing, and isobaric tags for relative and absolute quantitation analyses were performed to explore the mechanism by which wedelolactone promotes the chondrogenic differentiation of MSCs. We found that wedelolactone facilitates the chondrogenic differentiation of human induced pluripotent stem cell-derived MSCs and rat bone-marrow MSCs. Moreover, the forkhead box O (FOXO) signaling pathway was upregulated by wedelolactone during chondrogenic differentiation, and a FOXO1 inhibitor attenuated the effect of wedelolactone on chondrocyte differentiation. We determined that wedelolactone reduces enhancer of zeste homolog 2 (EZH2)-mediated histone H3 lysine 27 trimethylation of the promoter region of <i>FOXO1</i> to upregulate its transcription. Additionally, we found that wedelolactone represses miR-1271-5p expression, and that miR-1271-5p post-transcriptionally suppresses the expression of <i>FOXO1</i> that is dependent on the binding of miR-1271-5p to the <i>FOXO1</i> 3'-untranscribed region.</p><p><strong>Conclusions: </strong>These results indicate that wedelolactone suppresses the activity of EZH2 to facilitate the chondrogenic differentiation of MSCs by activating the FOXO1 signaling pathway. Wedelolactone may therefore improve cartilage regeneration in diseases characterized by inflammatory tissue destruction, such as OA.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 3","pages":"326-341"},"PeriodicalIF":2.3,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3d/08/ijsc-16-3-326.PMC10465333.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10124549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular Vesicles Derived from Mesenchymal Stem Cells as Cell-Free Therapy for Intrauterine Adhesion.","authors":"Chao Li,&nbsp;Yuanjing Hu","doi":"10.15283/ijsc21177","DOIUrl":"https://doi.org/10.15283/ijsc21177","url":null,"abstract":"<p><p>Intrauterine adhesion (IUA) can occur after trauma to the basal layer of the endometrium, contributing to severe complications in females, such as infertility and amenorrhea. To date, the proposed therapeutic strategies are targeted to relieve IUA, such as hysteroscopic adhesiolysis, Foley catheter balloon, and hyaluronic acid injection have been applied in the clinic. However, these approaches showed limited effects in alleviating endometrial fibrosis and thin endometrium. Mesenchymal stem cells (MSCs) can offer the potential for endometrium regeneration owing to reduce inflammation and release growth factors. On this basis, MSCs have been proposed as promising methods to treat intrauterine adhesion. However, due to the drawbacks of cell therapy, the possible therapeutic use of extracellular vesicles released by stem cells is raising increasing interest. The paracrine effect, mediated by MSCs derived extracellular vehicles (MSC-EVs), has recently been suggested as a mechanism for their therapeutic properties. Here, we summarizes the main pathological mechanisms involved in intrauterine adhesion, the biogenesis and characteristics of extracellular vesicles, explaining how these vesicles could provide new opportunities for MSCs.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 3","pages":"260-268"},"PeriodicalIF":2.3,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7d/38/ijsc-16-3-260.PMC10465336.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10124842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoxia Differentially Affects Chondrogenic Differentiation of Progenitor Cells from Different Origins.","authors":"Mira Hammad,&nbsp;Alexis Veyssiere,&nbsp;Sylvain Leclercq,&nbsp;Vincent Patron,&nbsp;Catherine Baugé,&nbsp;Karim Boumédiene","doi":"10.15283/ijsc21242","DOIUrl":"https://doi.org/10.15283/ijsc21242","url":null,"abstract":"<p><strong>Background and objectives: </strong>Ear cartilage malformations are commonly encountered problems in reconstructive surgery, since cartilage has low self-regenerating capacity. Malformations that impose psychological and social burden on one's life are currently treated using ear prosthesis, synthetic implants or autologous flaps from rib cartilage. These approaches are challenging because not only they request high surgical expertise, but also they lack flexibility and induce severe donor-site morbidity. Through the last decade, tissue engineering gained attention where it aims at regenerating human tissues or organs in order to restore normal functions. This technique consists of three main elements, cells, growth factors, and above all, a scaffold that supports cells and guides their behavior. Several studies have investigated different scaffolds prepared from both synthetic or natural materials and their effects on cellular differentiation and behavior.</p><p><strong>Methods and results: </strong>In this study, we investigated a natural scaffold (alginate) as tridimensional hydrogel seeded with progenitors from different origins such as bone marrow, perichondrium and dental pulp. In contact with the scaffold, these cells remained viable and were able to differentiate into chondrocytes when cultured in vitro. Quantitative and qualitative results show the presence of different chondrogenic markers as well as elastic ones for the purpose of ear cartilage, upon different culture conditions.</p><p><strong>Conclusions: </strong>We confirmed that auricular perichondrial cells outperform other cells to produce chondrogenic tissue in normal oxygen levels and we report for the first time the effect of hypoxia on these cells. Our results provide updates for cartilage engineering for future clinical applications.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 3","pages":"304-314"},"PeriodicalIF":2.3,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/55/db/ijsc-16-3-304.PMC10465331.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10124283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripheral Neuron-Organoid Interaction Induces Colonic Epithelial Differentiation via Non-Synaptic Substance P Secretion.","authors":"Young Hyun Che,&nbsp;In Young Choi,&nbsp;Chan Eui Song,&nbsp;Chulsoon Park,&nbsp;Seung Kwon Lim,&nbsp;Jeong Hee Kim,&nbsp;Su Haeng Sung,&nbsp;Jae Hoon Park,&nbsp;Sun Lee,&nbsp;Yong Jun Kim","doi":"10.15283/ijsc23026","DOIUrl":"https://doi.org/10.15283/ijsc23026","url":null,"abstract":"<p><strong>Background and objectives: </strong>The colonic epithelial layer is a complex structure consisting of multiple cell types that regulate various aspects of colonic physiology, yet the mechanisms underlying epithelial cell differentiation during development remain unclear. Organoids have emerged as a promising model for investigating organogenesis, but achieving organ-like cell configurations within colonic organoids is challenging. Here, we investigated the biological significance of peripheral neurons in the formation of colonic organoids.</p><p><strong>Methods and results: </strong>Colonic organoids were co-cultured with human embryonic stem cell (hESC)-derived peripheral neurons, resulting in the morphological maturation of columnar epithelial cells, as well as the presence of enterochromaffin cells. Substance P released from immature peripheral neurons played a critical role in the development of colonic epithelial cells. These findings highlight the vital role of inter-organ interactions in organoid development and provide insights into colonic epithelial cell differentiation mechanisms.</p><p><strong>Conclusions: </strong>Our results suggest that the peripheral nervous system may have a significant role in the development of colonic epithelial cells, which could have important implications for future studies of organogenesis and disease modeling.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 3","pages":"269-280"},"PeriodicalIF":2.3,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c0/01/ijsc-16-3-269.PMC10465334.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10498286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Notch is Not Involved in Physioxia-Mediated Stem Cell Maintenance in Midbrain Neural Stem Cells.","authors":"Anne Herrmann,&nbsp;Anne K Meyer,&nbsp;Lena Braunschweig,&nbsp;Lisa Wagenfuehr,&nbsp;Franz Markert,&nbsp;Deborah Kolitsch,&nbsp;Vladimir Vukicevic,&nbsp;Christiane Hartmann,&nbsp;Marlen Siebert,&nbsp;Monika Ehrhart-Bornstein,&nbsp;Andreas Hermann,&nbsp;Alexander Storch","doi":"10.15283/ijsc22168","DOIUrl":"https://doi.org/10.15283/ijsc22168","url":null,"abstract":"<p><strong>Background and objectives: </strong>The physiological oxygen tension in fetal brains (∼3%, physioxia) is beneficial for the maintenance of neural stem cells (NSCs). Sensitivity to oxygen varies between NSCs from different fetal brain regions, with midbrain NSCs showing selective susceptibility. Data on Hif-1α/Notch regulatory interactions as well as our observations that Hif-1α and oxygen affect midbrain NSCs survival and proliferation prompted our investigations on involvement of Notch signalling in physioxia-dependent midbrain NSCs performance.</p><p><strong>Methods and results: </strong>Here we found that physioxia (3% O₂) compared to normoxia (21% O₂) increased proliferation, maintained stemness by suppression of spontaneous differentiation and supported cell cycle progression. Microarray and qRT-PCR analyses identified significant changes of Notch related genes in midbrain NSCs after long-term (13 days), but not after short-term physioxia (48 hours). Consistently, inhibition of Notch signalling with DAPT increased, but its stimulation with Dll4 decreased spontaneous differentiation into neurons solely under normoxic but not under physioxic conditions.</p><p><strong>Conclusions: </strong>Notch signalling does not influence the fate decision of midbrain NSCs cultured <i>in vitro</i> in physioxia, where other factors like Hif-1α might be involved. Our findings on how physioxia effects in midbrain NSCs are transduced by alternative signalling might, at least in part, explain their selective susceptibility to oxygen.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 3","pages":"293-303"},"PeriodicalIF":2.3,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9e/35/ijsc-16-3-293.PMC10465337.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10497727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Xenogeneic Substances on the Glycan Profiles and Electrophysiological Properties of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.","authors":"Yong Guk Kim,&nbsp;Jun Ho Yun,&nbsp;Ji Won Park,&nbsp;Dabin Seong,&nbsp;Su-Hae Lee,&nbsp;Ki Dae Park,&nbsp;Hyang-Ae Lee,&nbsp;Misun Park","doi":"10.15283/ijsc22158","DOIUrl":"https://doi.org/10.15283/ijsc22158","url":null,"abstract":"<p><strong>Background and objectives: </strong>Human induced pluripotent stem cell (hiPSC)-derived cardiomyocyte (CM) hold great promise as a cellular source of CM for cardiac function restoration in ischemic heart disease. However, the use of animal-derived xenogeneic substances during the biomanufacturing of hiPSC-CM can induce inadvertent immune responses or chronic inflammation, followed by tumorigenicity. In this study, we aimed to reveal the effects of xenogeneic substances on the functional properties and potential immunogenicity of hiPSC-CM during differentiation, demonstrating the quality and safety of hiPSC-based cell therapy.</p><p><strong>Methods and results: </strong>We successfully generated hiPSC-CM in the presence and absence of xenogeneic substances (xeno-containing (XC) and xeno-free (XF) conditions, respectively), and compared their characteristics, including the contractile functions and glycan profiles. Compared to XC-hiPSC-CM, XF-hiPSC-CM showed early onset of myocyte contractile beating and maturation, with a high expression of cardiac lineage-specific genes (<i>ACTC1</i>, <i>TNNT2</i>, and <i>RYR2</i>) by using MEA and RT-qPCR. We quantified N-glycolylneuraminic acid (Neu5Gc), a xenogeneic sialic acid, in hiPSC-CM using an indirect enzyme-linked immunosorbent assay and liquid chromatography-multiple reaction monitoring- mass spectrometry. Neu5Gc was incorporated into the glycans of hiPSC-CM during xeno-containing differentiation, whereas it was barely detected in XF-hiPSC-CM.</p><p><strong>Conclusions: </strong>To the best of our knowledge, this is the first study to show that the electrophysiological function and glycan profiles of hiPSC-CM can be affected by the presence of xenogeneic substances during their differentiation and maturation. To ensure quality control and safety in hiPSC-based cell therapy, xenogeneic substances should be excluded from the biomanufacturing process.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"16 3","pages":"281-292"},"PeriodicalIF":2.3,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fe/4b/ijsc-16-3-281.PMC10465332.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10497728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}