AIMS Cell and Tissue Engineering最新文献

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Human fetal kidney cells regenerate acellular porcine kidneys via upregulation of key transcription factors involved in kidney developmentRunning title: Regeneration of porcine kidneys 人胎儿肾细胞通过上调参与肾脏发育的关键转录因子来再生无细胞的猪肾脏

AIMS Cell and Tissue Engineering Pub Date : 2019-07-08 DOI: 10.3934/CELLTISSUE.2019.1.26

V. Kuna, S. Paul, Bo Xu, R. Sjöback, S. Sumitran‐Holgersson

{"title":"Human fetal kidney cells regenerate acellular porcine kidneys via upregulation of key transcription factors involved in kidney developmentRunning title: Regeneration of porcine kidneys","authors":"V. Kuna, S. Paul, Bo Xu, R. Sjöback, S. Sumitran‐Holgersson","doi":"10.3934/CELLTISSUE.2019.1.26","DOIUrl":"https://doi.org/10.3934/CELLTISSUE.2019.1.26","url":null,"abstract":"Interaction between organ-specific stem cells and extracellular matrix (ECM) is crucial for regeneration. We therefore, investigated novel stem cells markers in human kidney and verified the potential of human fetal kidney cells (hFKC) to repopulate decellularized porcine kidneys. Adult and fetal human kidneys were stained by immunohistochemistry for putative stem cell markers. In addition, hFKC were isolated and characterized phenotypically and by gene expression. Furthermore, whole porcine kidneys were decellularized using detergents, cut into 1 mm slices, seeded with hFKC, cultured for 14 days and characterized by histology and qPCR. We found that, decellularized porcine kidneys showed significant loss of DNA but preserved some ECM components. Human fetal kidneys including hFKC expressed stem cell markers CD133, DLK-1, EPCAM and ephrin receptor EphA6. Interestingly, EphA7 and SIX2 were markedly expressed only in fetus. Furthermore, in fetal kidneys EphA7 was co-expressed with DLK-1. Recellularized kidney pieces showed cell infiltration, growing in orchestrated fashion distributed around the scaffold. These pieces also demonstrated cells expressing CK8, CK18, DLK-1, CD133, EphA7, EphB3, PCNA, podocin and increased levels of transcriptional factors in kidney development (SIX2, EYA1, CITED1, LHX1, SALL1, DLK-1 and WT1). We conclude that decellularized porcine kidneys support the culture, proliferation of hFKC and regenerate by upregulation of transcription factors. We suggest that expanded hFKC may be the ideal cell source for whole kidney regeneration in the future. We also postulate EphA7 might be a novel stem cell marker in kidneys.","PeriodicalId":110662,"journal":{"name":"AIMS Cell and Tissue Engineering","volume":"55 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114742688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Modeling rare pediatric neurogenetic disorders with IPSCs 用IPSCs模拟罕见的儿童神经遗传疾病

AIMS Cell and Tissue Engineering Pub Date : 2019-04-25 DOI: 10.3934/CELLTISSUE.2019.1.1

Jaemin Kim, D. Nonis, M. G. Otero, T. Pierson

{"title":"Modeling rare pediatric neurogenetic disorders with IPSCs","authors":"Jaemin Kim, D. Nonis, M. G. Otero, T. Pierson","doi":"10.3934/CELLTISSUE.2019.1.1","DOIUrl":"https://doi.org/10.3934/CELLTISSUE.2019.1.1","url":null,"abstract":"Intensive research has been performed to identify the pathological mechanisms of many pediatric neurogenetic disorders and to identify potential therapeutic targets. Although research into many pediatric neurological disorders has provided tremendous insight into the mechanisms of disease, effective treatments remain elusive. A significant impediment to progress has been a lack of thorough disease models. Transgenic/knockout animal models have been very valuable in determining the mechanisms of many neurogenetic disorders; however, these models cannot always mimic human-specific pathology and can be inadequate in representing human pathogenesis. This can be especially true for diseases of the nervous system. Alternatively, human patient-derived nervous tissue can be dangerous to acquire and difficult to propagate. The development of patient-derived induced pluripotent stem cells (IPSCs) has given researchers a fresh means of modeling these disorders with renewable human cells that can be used to generate neurons and glia. IPSCs are somatic cells that are reprogrammed back to a pluripotent stage, which can provide an unlimited source of human cells possessing patient-specific genetic mutations. Their potential to be differentiated into any cell type enables them to be a flexible platform to investigate neurogenetic disease. Of course, efficient methods for differentiating IPSCs into homogeneous populations of somatic cells must be established to provide the “disease-in-a-dish” systems. We will discuss the current methods for generating IPSC-derived neural cells to model pediatric neurogenetic disorders, as well as provide examples of the disorders that have been studied that include several neurodevelopmental and neurodegenerative disorders (Rett syndrome, spinal muscular atrophy, hereditary spastic paraplegias, and leukodystrophies). In addition, we provide examples on how patient-specific neural cells can be used in therapeutic development with high-throughput drug screening platforms or with correction via genome editing.","PeriodicalId":110662,"journal":{"name":"AIMS Cell and Tissue Engineering","volume":"32 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126299819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1