Stem cells and development最新文献

{"title":"Bioengineering Human Cartilage-Bone Tissues for Modeling of Osteoarthritis.","authors":"Josephine Y Wu,&nbsp;Gordana Vunjak-Novakovic","doi":"10.1089/scd.2021.0317","DOIUrl":"https://doi.org/10.1089/scd.2021.0317","url":null,"abstract":"<p><p>Osteoarthritis (OA) is the most common joint disease worldwide, yet we continue to lack an understanding of disease etiology and pathology and effective treatment options. Essential to tissue homeostasis, disease pathogenesis, and therapeutic responses are the stratified organization of cartilage and cross talk at the osteochondral junction. Animal models may capture some of these features, but to establish clinically consistent therapeutics, there remains a need for high-fidelity models of OA that meet all the above requirements in a human patient-specific manner. In vitro bioengineered cartilage-bone tissue models could be developed to recapitulate physiological interactions with human cells and disease-initiating factors. In this study, we highlight human induced pluripotent stem cells (hiPSCs) as the advantageous cell source for these models and review approaches for chondrogenic fate specification from hiPSCs. To achieve native-like stratified cartilage organization with cartilage-bone interactions, spatiotemporal cues mimicking development can be delivered to engineered tissues by patterning of the cells, scaffold, and environment. Once healthy and native-like cartilage-bone tissues are established, an OA-like state can be induced through cytokine challenge or injurious loading. Bioengineered cartilage-bone tissues fall short of recapitulating the full complexity of native tissues, but have demonstrated utility in elucidating some mechanisms of OA progression and enabled screening of candidate therapeutics in patient-specific models. With rapid progress in stem cells, tissue engineering, imaging, and high-throughput omics research in recent years, we propose that advanced human tissue models will soon offer valuable contributions to our understanding and treatment of OA.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9398485/pdf/scd.2021.0317.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9913212","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":"Minimally Invasive Cell-Based Therapy for Symptomatic Bone Marrow Lesions of the Knee: A Prospective Clinical Study at 1 Year.","authors":"Ignacio Dallo,&nbsp;Riccardo D'Ambrosi,&nbsp;Dawid Szwedowski,&nbsp;Ali Mobasheri,&nbsp;Alberto Gobbi","doi":"10.1089/scd.2021.0283","DOIUrl":"https://doi.org/10.1089/scd.2021.0283","url":null,"abstract":"<p><p>Bone marrow lesions (BMLs) are typical findings in magnetic resonance imaging present in different pathologies, such as spontaneous insufficiency fractures, osteonecrosis, transient BML syndromes, osteoarthritis, and trauma. The etiology and evolution of BMLs in multiple conditions remain unclear. There is still no gold standard protocol for the treatment of symptomatic BMLs in the knee. The biologic augmentation by Osteo Core Plasty™ is a new treatment modality showing promising results reducing pain with the aim to stop the progression of the disease. The purpose of this prospective study is to report the clinical outcomes and safety of Osteo Core Plasty for the treatment of symptomatic BMLs in the knee. Fifteen patients with symptomatic BMLs of the knee treated with the Osteo Core Plasty technique were included and followed prospectively for a minimum of 12 months. Each patient was evaluated before the surgery and respectively at 6 and 12 months using the Tegner Score, Marx Score, the International Knee Documentation Committee, the Knee Injury and Osteoarthritis Outcome Score divided in pain, activity daily living and quality of life subscale, and the Visual Analog Scale for pain. All clinical scores except Tegner and Marx score showed an overall statistically significant improvement through the entire follow-up (<i>P</i> < 0.05) and a significant improvement (<i>P</i> < 0.05) between each follow-up period (T₀ vs. T₁; T₀ vs. T₂; T₁ vs. T₂). No complications were reported. These preliminary results confirm that biological subchondral bone augmentation by Osteo Core Plasty technique is a safe and effective minimally invasive treatment option for symptomatic BMLs in the knee at 1-year follow-up. There is still a need for high-quality randomized controlled trials studies and systematic reviews in the future to enhance further treatment strategies in preventing or treating BMLs of the knee.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39855584","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}

{"title":"An Updated View on Temporomandibular Joint Degeneration: Insights from the Cell Subsets of Mandibular Condylar Cartilage.","authors":"Minglu Xu,&nbsp;Xuyang Zhang,&nbsp;Yao He","doi":"10.1089/scd.2021.0324","DOIUrl":"https://doi.org/10.1089/scd.2021.0324","url":null,"abstract":"<p><p>The high prevalence of temporomandibular joint osteoarthritis (TMJOA), which causes joint dysfunction, indicates the need for more effective methods for treatment and repair. Mandibular condylar cartilage (MCC), a typical fibrocartilage that experiences degenerative changes during the development of TMJOA, has become a research focus and therapeutic target in recent years. MCC is composed of four zones of cells at various stages of differentiation. The cell subsets in MCC exhibit different physiological and pathological characteristics during development and in TMJOA. Most studies of TMJOA are mainly concerned with gene regulation of pathological changes. The corresponding treatment targets with specific cell subsets in MCC may provide more accurate and reliable results for cartilage repair and TMJOA treatment. In this review, we summarized the current research progress on the cell subsets of MCC from the perspective of MCC development and degeneration. We hope to provide a reference for further exploration of the pathological process of TMJOA and improvement of TMJOA treatment.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39921890","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}

{"title":"Chondroprotective Effects of Periodontal Ligament-Derived Stem Cells Conditioned Medium on Articular Cartilage After Impact Injury.","authors":"Logan A Beatty,&nbsp;Kailey L Mansour,&nbsp;Evan J Bryant,&nbsp;Franklin Garcia-Godoy,&nbsp;Domingo Santos Pantaleon,&nbsp;Yoh Sawatari,&nbsp;Chun-Yuh Huang,&nbsp;Franklin Garcia-Godoy","doi":"10.1089/scd.2022.0130","DOIUrl":"https://doi.org/10.1089/scd.2022.0130","url":null,"abstract":"<p><p>Paracrine factors secreted in the conditioned media (CMs) of periodontal ligament-derived stem cells (PDLSCs) have been shown to downregulate inflammatory effects of interleukin (IL)-1β on chondrocytes wherein milk fat globule-epidermal growth factor 8 (MFG-E8) is one of the PDLSCs' highly secretory proteins. Therefore, the objective of this study was to investigate the ability of PDLSC CMs and MFG-E8 to reduce the inflammatory effects of impact injury on porcine talar articular cartilage (AC) and IL-1β on chondrocytes, respectively. Stem cells were isolated from human periodontal ligaments. The MFG-E8 content in CM collected at 5% and 20% oxygen was measured by ELISA assay and compared across subcultures and donors. AC samples were divided into three groups: control, impact, and impact+CM. Chondrocytes were isolated from pig knees and were divided into three groups: control, IL-1β, and IL-1β+MFG-E8. Gene expression data were analyzed by reverse transcription-polymerase chain reaction. It was found that impact load and IL-1β treatment upregulated IL-1β, TNF-α, ADAMTS-4, and ADAMTS-5 gene expression in AC and chondrocytes, respectively. PDLSCs-CM prevented the upregulation of all four genes due to impact, whereas MFG-E8 prevented upregulation of IL-1β, ADAMTS-4, and ADAMTS-5 in chondrocytes, but it did not prevent TNF-α upregulation. There were no significant differences in MFG-E8 content in CM among oxygen levels, passage numbers, or donors. The findings suggested that MFG-E8 is an effective anti-inflammatory agent contributing to the chondroprotective effects of PDLSCs-CM on acutely injured AC. Thus, introducing PDLSCs-CM to sites of acute traumatic AC injury could prevent the development of post-traumatic osteoarthritis.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40164412","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}

{"title":"Methodological Quality and Risk of Bias of Systematic Reviews and Meta-Analyses on Stem Cells for Knee Osteoarthritis: A Cross-Sectional Survey.","authors":"Aifeng Liu,&nbsp;Weijie Yu,&nbsp;Jixin Chen,&nbsp;Tianci Guo,&nbsp;Puyu Niu,&nbsp;Huichuan Feng,&nbsp;Yizhen Jia","doi":"10.1089/scd.2022.0060","DOIUrl":"https://doi.org/10.1089/scd.2022.0060","url":null,"abstract":"<p><p>Clinical guidelines need high-quality studies to support clinical decision making, in which the evidence often was collected from systematic reviews (SRs) and/or meta-analyses (MAs). At present, the methodological quality and risk of bias (RoB) of SRs/MAs on stem cell therapy for the treatment of knee osteoarthritis (KOA) has been poorly investigated. This study aims to strictly evaluate the methodological quality and RoB in SRs/MAs of stem cell therapy for KOA. Four electronic databases (PubMed, Embase, Cochrane Library, and Web of Science databases) were searched, from inception to October 5, 2021. SRs/MAs involving randomized control trials or cohort studies on stem cell therapy for the treatment of KOA were included. The methodological quality and RoB were assessed using AMSTAR 2 and ROBIS tool, respectively. In total, 22 SRs/MAs were included. According to the results obtained by AMSTAR 2 tool, all SRs/MAs were rated as \"Critically low.\" Main methodological weaknesses were as follows: up to 81.82% did not meet protocol registration requirements, only 13.64% provided a list of excluded studies and justification, and 13.64% investigated and discussed the publication bias. ROBIS-based RoB assessment showed that all the SRs/MAs were rated as \"High.\" Besides, the lack of following the implementation of the PRISMA reporting guideline seems to reduce the methodological quality of the studies. The overall methodological quality of the SRs/MAs concerning the application of stem cell therapy in treating KOA is \"Critically low,\" while the RoB is high. It is difficult to provide effective evidence for the formulation of guidelines for KOA treatment. We suggest that the relevant methodological quality assessment should be carried out in the future before the SRs/MAs are used as clinical evidence. In addition, it may be necessary for many journals to include the checklist with a submitted article. PROSPERO registration number: CRD42021246924.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40313935","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}

{"title":"<i>Retraction of:</i> Hyaluronic Acid and Thrombin Upregulate MT1-MMP Through PI3K and Rac-1 Signaling and Prime the Homing-Related Responses of Cord Blood Hematopoietic Stem/Progenitor Cells (doi: 10.1089/scd.2010.0118).","authors":"","doi":"10.1089/scd.2010.0118.retract","DOIUrl":"https://doi.org/10.1089/scd.2010.0118.retract","url":null,"abstract":"","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10331150/pdf/scd.2010.0118.retract.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9765956","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":"Identification of novel multipotent stem cells in mouse spinal cord following traumatic injury.","authors":"Y. Kuramoto, Toshinori Takagi, Yuki Takeda, Saujanya Rajbhandari, Yasunori Yoshida, T. Nakagomi, Shinichi Yoshimura","doi":"10.1089/scd.2021.0297","DOIUrl":"https://doi.org/10.1089/scd.2021.0297","url":null,"abstract":"We showed that injury-induced multipotent stem cells (iSCs) emerge in the brain after stroke. These brain-derived iSCs (B-iSCs) can differentiate into various lineages, including neurons. This study aimed to determine whether similar stem cells can be induced even after non-ischemic injuries, such as trauma to the spinal cord. We characterized these cells, mainly focusing on their stemness, multipotency, and neuronal differentiation activities. Spinal cord injury was produced using forceps in adult mice. On day 3 after spinal cord injury, samples were obtained from the injured areas. Spinal cord sections were subjected to histological analyses. Cells were isolated and assessed for proliferative activities, immunohistochemistry, RT-PCR, FACS, and microarray analysis. Although nerve cell morphology was disrupted within the injured spinal cord, our histological observations revealed the presence of cells expressing stem cells, such as nestin and Sox2 in these areas. In addition, cells extracted from injured areas exhibited high proliferative abilities. These cells also expressed markers of both neural stem cells (e.g., nestin, Sox2) and multipotent stem cells (e.g., Sox2, c-myc, Klf4). They differentiated into adipocytes, osteocytes and chondrocytes, as well as neuronal cells. Microarray analysis further identified similar properties between spinal cord (SC)-derived iSCs and B-iSCs. However, SC-iSCs revealed specific genes related to the regulation of stemness and neurogenesis. We identified similar features related to multipotency in SC-iSCs compared to B-iSCs, including neuronal differentiation potential. Although the differences between SC-iSCs and B-iSCs remain largely undetermined, the present study shows that iSCs can develop even after non-ischemic injuries such as trauma. This phenomenon can occur outside the brain within the CNS.","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2022-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45062968","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}

{"title":"Equine platelet lysate gel: a matrix for mesenchymal stem cell delivery.","authors":"Maria C Naskou, J. Tyma, J. Gordon, Alysha Berezny, Hannah Kemelmakher, Anna Chocallo Richey, J. Peroni","doi":"10.1089/scd.2022.0097","DOIUrl":"https://doi.org/10.1089/scd.2022.0097","url":null,"abstract":"A variety of bio-scaffolds have been developed as carriers for the delivery of Mesenchymal Stem Cells (MSCs) however many of them are unable to provide direct cell nourishment, a critical factor for survival and retention of MSCs at the site of delivery. Platelet lysate (PL) is a plasma derived product rich in growth factors, that can be turned into a gel matrix following the addition of calcium chloride. Our objective was to characterize growth factor and cytokine release of equine PL gel (ePL gel) encapsulated with MSCs over time and to measure the viability and proliferation of ePL gel-encapsulated MSCs for up to 14 days. Release of interleukin-1β (IL-1β), interleukin-10 (IL-10), transforming growth factor beta (TGF-β), vascular endothelial growth factor (VEGF), and platelet derived growth factor (PDGF-BB), as well as fibrinogen degradation, were measured from ePL gel with and without equine bone marrow derived MSCs and compared to MSCs in monolayer. MSC proliferation and viability within the gel were assessed up to 14 days. Compared to monolayer MSC cultures, significantly higher concentrations of IL-1β, IL-10, and TGF-β were measured from supernatants collected from ePL gel containing MSCs at various time points. Significantly lower concentrations of PDGF-BB were measured in the supernatant when MSCs were incorporated in ePL gel while VEGF tended to be increased compared to MSCs in monolayer. Incorporation in ePL gel for up to 14 days did not appear to affect viability and proliferation rates of MSCs as these were found to be similar to those measured in monolayer cell culture. ePL gel may have the potential to serve as bio-scaffold for MSC delivery since it appears to support the proliferation and viability of MSCs for up to 14 days.","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2022-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45623926","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}

{"title":"MicroRNA-7a2 is required for the development of pituitary stem cells.","authors":"Jinglin Zhang, Yewen Zhou, Jiajia Guo, Liuhui Li, Hui Liu, Chenyang Lu, Ying Jiang, S. Cui","doi":"10.1089/scd.2022.0023","DOIUrl":"https://doi.org/10.1089/scd.2022.0023","url":null,"abstract":"The pituitary gland is inhabited by a subpopulation of SOX2+ stem cells. However, the regulatory mechanisms underlying pituitary stem cell development remain poorly understood. Here, we demonstrate that microRNA-7a (miR-7a) is enriched in the developing pituitary and is spatiotemporally expressed in the pituitary stem cells. Constitutive deletion of miR-7a2 in mice results in pituitary dysplasia emerging during birth, which is primarily manifested as malformed anterior lobes. Using immunofluorescence, immunohistochemistry or in situ hybridization, we observe that the specification of hormone-expressing cells is not impeded post miR-7a2 deletion at birth, although the terminal differentiation of gonadotropes is inhibited. Further investigation of neonatal and adult pituitaries in miR-7a2 knockout mice reveals an expansion of the SOX2+ pituitary stem cell compartment. The inhibition of epithelial-mesenchymal like transition seems to be responsible for this phenotype, rather than abnormal proliferation or apoptosis. Furthermore, our data suggest that Gli3 and Ckap4 are potential targets of miR-7a in pituitary stem cells. In summary, our results identify miR-7a2 as a crucial factor involved in pituitary stem cell development.","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2022-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45809607","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}

{"title":"Using Live Imaging and Fluorescence Ubiquitinated Cell Cycle Indicator Embryonic Stem Cells to Distinguish G1 Cell Cycle Delays for General Stressors like Perfluoro-Octanoic Acid and Hyperosmotic Sorbitol or G2 Cell Cycle Delay for Mutagenic Stressors like Benzo(a)pyrene.","authors":"Mohammed Abdulhasan, Ximena Ruden, Teya Marben, Sean Harris, Douglas M Ruden, Awoniyi O Awonuga, Elizabeth E Puscheck, Daniel A Rappolee","doi":"10.1089/scd.2021.0330","DOIUrl":"10.1089/scd.2021.0330","url":null,"abstract":"<p><p>Lowest observable adverse effects level (LOAEL) is a standard point-of-departure dose in toxicology. However, first observable adverse effects level (FOAEL) was recently reported and is used, in this study, as one criterion to detect a mutagenic stimulus in a live imager. Fluorescence ubiquitinated cell cycle indicator (FUCCI) embryonic stem cells (ESC) are green in the S-G2-M phase of the cell cycle and not green in G1-phase. Standard media change here is a mild stress that delays G1-phase and media change increases green 2.5- to 5-fold. Since stress is mild, media change rapidly increases green cell number, but higher stresses of environmental toxicants and positive control hyperosmotic stress suppress increased green after media change. Perfluoro-octanoic acid (PFOA) and diethyl phthalate (DEP) previously suppressed progression of nongreen to green cell cycle progression. Here, bisphenol A (BPA), cortisol, and positive control hyperosmotic sorbitol also suppress green fluorescence, but benzo(a)pyrene (BaP) at high doses (10 μM) increases green fluorescence throughout the 74-h exposure. Since any stress can affect many cell cycle phases, messenger RNA (mRNA) markers are best interpreted in ratios as dose-dependent mutagens increase in G2/G1 and nonmutagens increase G1/G2. After 74-h exposure, RNAseq detects G1 and G2 markers and increasing BaP doses increase G2/G1 ratios but increasing hyperosmotic sorbitol and PFOA doses increase G1/G2 marker ratios. BaP causes rapid green increase in FOAEL at 2 h of stimulus, whereas retinoic acid caused significant green fluorescence increases only late in culture. Using a live imager to establish FOAEL and G2 delay with FUCCI ESC is a new method to allow commercial and basic developmental biologists to detect drugs and environmental stimuli that are mutagenic. Furthermore, it can be used to test compounds that prevent mutations. In longitudinal studies, uniquely provided by this viable reporter and live imager protocol, follow-up can be done to test whether the preventative compound itself causes harm.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9232235/pdf/scd.2021.0330.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9912237","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}