{"title":"Wharton's Jelly Mesenchymal Stem Cells: Shaping the Future of Osteoarthritis Therapy with Advancements in Chitosan-Hyaluronic Acid Scaffolds.","authors":"Ahed Ghamrawi, Rasha Basso, Nour Shakik, Lara Haddad, Zeina Nasr, Chaza Harmouch","doi":"10.1089/scd.2024.0033","DOIUrl":"https://doi.org/10.1089/scd.2024.0033","url":null,"abstract":"<p><p>This review explores the potential of Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) in cartilage regeneration and osteoarthritis treatment. It covers key factors influencing chondrogenesis, including growth factors, cytokines, and hypoxia, focusing on precise timing. The effectiveness of three-dimensional cultures and scaffold-based strategies in chondrogenic differentiation is discussed. Specific biomaterials such as chitosan and hyaluronic acid are highlighted for tissue engineering. The document reviews clinical applications, incorporating evidence from animal research and early trials and molecular and histological assessments of chondrogenic differentiation processes. It addresses challenges and strategies for optimizing MSC-derived chondrocyte therapy, emphasizing the immunomodulatory properties of these cells. The review concludes as a comprehensive road map for future research and clinical applications in regenerative medicine.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142740863","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}
Yaping Xu, Xiangli Zhang, Zhikun Fu, Yan Dong, Yuexin Yu, Yingtian Liu, Ziyu Liu, Jinfu Chen, Yao Yao, Yan Chen, Jer Ping Ooi, Bakiah Shaharuddin, Bin Yang, Jun Jie Tan, Zhikun Guo
{"title":"Intrapericardial Administration of Human Pericardial Fluid Cells Improves Cardiac Functions in Rats with Heart Failure.","authors":"Yaping Xu, Xiangli Zhang, Zhikun Fu, Yan Dong, Yuexin Yu, Yingtian Liu, Ziyu Liu, Jinfu Chen, Yao Yao, Yan Chen, Jer Ping Ooi, Bakiah Shaharuddin, Bin Yang, Jun Jie Tan, Zhikun Guo","doi":"10.1089/scd.2024.0072","DOIUrl":"10.1089/scd.2024.0072","url":null,"abstract":"<p><p>Heart failure (HF) is still the main cause of mortality worldwide. This study investigated the characteristics of human pericardial fluid-derived cells (hPFCs) and their effects in treating doxorubicin (DOX)-induced HF rats through intrapericardial injection. hPFCs were isolated from patients who underwent heart transplantation (<i>N</i> = 5). These cells that primarily expressed SCA-1, NANOG, and mesenchymal markers, CD90, CD105, and CD73, were able to form adipocytes, osteoblasts, and cardiomyocytes in vitro. Passage 3 hPFCs (2.5 × 10<sup>5</sup> cells/heart) were injected into the pericardial cavity of the DOX-injured rat hearts, significantly improving cardiac functions after 4 weeks. The tracked and engrafted red fluorescent protein-tagged hPFCs coexpressed cardiac troponin T and connexin 43 after 4 weeks in the host myocardium. This observation was also coupled with a significant reduction in cardiac fibrosis following hPFC treatment <i>(P</i> < 0.0001 vs. untreated). The elevated inflammatory cytokines interleukin (IL)-6, IL-10, and tumor necrosis factor-α in the DOX-treated hearts were found to be significantly reduced (<i>P</i> < 0.001 vs. untreated), while the regional proangiogenic vascular endothelial growth factor A (VEGFA) level was increased in the hPFC-treated group after 4 weeks (<i>P</i> < 0.05 vs. untreated). hPFCs possess stem cell characteristics and can improve the cardiac functions of DOX-induced HF rats after 4 weeks through pericardial administration. The improvements were attributed to a significant reduction in cardiac fibrosis, inflammation, and elevated regional proangiogenesis factor VEGFA, with evidence of cellular engraftment and differentiation in the host myocardium.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"616-629"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142001610","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}
{"title":"The Construction of Stem Cell-Induced Hepatocyte Model and Its Application in Evaluation of Developmental Hepatotoxicity of Environmental Pollutants.","authors":"Nadire Nijiati, Dilixiati Wubuli, Xiaobing Li, Zidong Zhou, Mulati Julaiti, Pengfei Huang, Bowen Hu","doi":"10.1089/scd.2024.0117","DOIUrl":"10.1089/scd.2024.0117","url":null,"abstract":"<p><p>Stem cells, with their ability to self-renew and differentiate into various cell types, are a unique and valuable resource for medical research and toxicological studies. The liver is the most crucial metabolic organ in the human body and serves as the primary site for the accumulation of environmental pollutants. Enrichment with environmental pollutants can disrupt the early developmental processes of the liver and have a significant impact on liver function. The liver comprises a complex array of cell types, and different environmental pollutants have varying effects on these cells. Currently, there is a lack of well-established research models that can effectively demonstrate the mechanisms by which environmental pollutants affect human liver development. The emergence of liver cells and organoids derived from stem cells offers a promising tool for investigating the impact of environmental pollutants on human health. Therefore, this study systematically reviewed the developmental processes of different types of liver cells and provided an overview of studies on the developmental toxicity of various environmental pollutants using stem cell models.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"575-585"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141899271","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}
Jingyu Wang, Fengqing Zhu, Renru Luo, Yingyin Cui, Ziyu Zhang, Mengling Xu, Yuanyuan Zhao, Yonghui He, Wenqing Yang, Nianle Li, Zhu Zhu, Yingshan Chen, Tao Wang, Xuan Jiang, Chuwen Lin
{"title":"YAP Alleviates Pulmonary Fibrosis Through Promoting Alveolar Regeneration via Modulating the Stemness of Alveolar Type 2 Cells.","authors":"Jingyu Wang, Fengqing Zhu, Renru Luo, Yingyin Cui, Ziyu Zhang, Mengling Xu, Yuanyuan Zhao, Yonghui He, Wenqing Yang, Nianle Li, Zhu Zhu, Yingshan Chen, Tao Wang, Xuan Jiang, Chuwen Lin","doi":"10.1089/scd.2024.0101","DOIUrl":"10.1089/scd.2024.0101","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with no cure except transplantation. Abnormal alveolar epithelial regeneration is a key driver of IPF development. The function of Yes1 Associated Transcriptional Regulator (YAP) in alveolar regeneration and IPF pathogenesis remains elusive. Here, we first revealed the activation of YAP in alveolar epithelium 2 cells (AEC2s) from human IPF lungs and fibrotic mouse lungs. Notably, conditional deletion of YAP in mouse AEC2s exacerbated bleomycin-induced pulmonary fibrosis. Intriguingly, we showed in both conditional knockout mice and alveolar organoids that YAP deficiency impaired AEC2 proliferation and differentiation into alveolar epithelium 1 cells (AEC1s). Mechanistically, YAP regulated expression levels of genes associated with cell cycle progression and AEC1 differentiation. Furthermore, overexpression of YAP in vitro promoted cell proliferation. These results indicate the critical role of YAP in alveolar regeneration and IPF pathogenesis. Our findings provide new insights into the regulation of alveolar regeneration and IPF pathogenesis, paving the road for developing novel treatment strategies.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"586-594"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141908786","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}
Meilin Hu, Ruiqi Liu, Xiaoyu Chen, Shen Yan, Jian Gao, Yao Zhang, Di Wu, Lu Sun, Zhi Jia, Guangyunhao Sun, Dayong Liu
{"title":"Metabolomics Dysfunction in Replicative Senescence of Periodontal Ligament Stem Cells Regulated by AMPK Signaling Pathway.","authors":"Meilin Hu, Ruiqi Liu, Xiaoyu Chen, Shen Yan, Jian Gao, Yao Zhang, Di Wu, Lu Sun, Zhi Jia, Guangyunhao Sun, Dayong Liu","doi":"10.1089/scd.2024.0112","DOIUrl":"10.1089/scd.2024.0112","url":null,"abstract":"<p><p>Periodontal ligament mesenchymal stem cells (PDLSCs) are a promising cell resource for stem cell-based regenerative medicine in dentistry, but they inevitably acquire a senescent phenotype after prolonged in vitro expansion. The key regulators of PDLSCs during replicative senescence remain unclear. Here, we sought to elucidate the role of metabolomic changes in determining the cellular senescence of PDLSCs. PDLSCs were cultured to passages 4, 10, and 20. The senescent phenotypes of PDLSCs were detected, and metabolomics analysis was performed. We found that PDLSCs manifested senescence phenotype during passaging. Metabolomics analysis showed that the metabolism of replicative senescence in PDLSCs varied significantly. The AMP-activated protein kinase (AMPK) signaling pathway was closely related to adenosine monophosphate (AMP) levels. The AMP:ATP ratio increased in senescent PDLSCs; however, the levels of p-AMPK, <i>FOXO1</i> and <i>FOXO3a</i> decreased with senescence. We treated PDLSCs with an activator of the AMPK pathway (AICAR) and observed that the phosphorylated AMPK level at P20 PDLSCs was partially restored. These data delineate that the metabolic process of PDLSCs is active in the early stage of senescence and attenuated in the later stages of senescence; however, the sensitivity of AMPK phosphorylation sites is impaired, causing senescent PDLSCs to fail to respond to changes in energy metabolism.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"607-615"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142305275","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}
Xin Shao, Fan Wu, Yang Song, Rongrong Kong, Shuang Wang, Liying Wang
{"title":"The Effects of Different Developmental Stages on Bone Regeneration of Periodontal Ligament Stem Cells and Periodontal Ligament Cell Sheets In Vitro and Vivo.","authors":"Xin Shao, Fan Wu, Yang Song, Rongrong Kong, Shuang Wang, Liying Wang","doi":"10.1089/scd.2024.0087","DOIUrl":"10.1089/scd.2024.0087","url":null,"abstract":"<p><p>Periodontal ligament stem cells (PDLSCs) have broad applications in tissue engineering and regeneration. However, the function of PDLSCs changes in different microenvironments. This study aimed to explore the effects of different developmental stages on the biological characteristics of PDLSCs. Here, PDLSCs were successfully cultured from the periodontal tissues of various groups, including a group with immature roots, a young group with mature roots, and an aging group with mature roots. By comparing the results of the three experimental groups, we found that the donors with immature roots exhibited the best proliferative ability and osteogenic differentiation, whereas the aging group demonstrated the worst proliferation. The trend for adipogenic differentiation was the opposite to that for osteogenic differentiation. The cell sheet and in vivo experiments revealed that in the immature root group, the cells produced more extracellular matrix and new bone and better absorbed the implant materials. These results indicate that PDLSCs perform various functions at different stages of development. In clinical applications of PDLSCs for periodontal regeneration, donors with incompletely developed roots have stronger biological characteristics.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"595-606"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141891454","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}
{"title":"Dtx2 Deficiency Induces Ependymo-Radial Glial Cell Proliferation and Improves Spinal Cord Motor Function Recovery.","authors":"Hao-Yuan Chen, Yin-Cheng Huang, Tu-Hsueh Yeh, Chia-Wei Chang, Yang-Jin Shen, Yi-Chieh Chen, Mu-Qun Sun, Yi-Chuan Cheng","doi":"10.1089/scd.2023.0247","DOIUrl":"10.1089/scd.2023.0247","url":null,"abstract":"<p><p>Traumatic injury to the spinal cord can lead to significant, permanent disability. Mammalian spinal cords are not capable of regeneration; in contrast, adult zebrafish are capable of such regeneration, fully recovering motor function. Understanding the mechanisms underlying zebrafish neuroregeneration may provide useful information regarding endogenous regenerative potential and aid in the development of therapeutic strategies in humans. DELTEX proteins (DTXs) regulate a variety of cellular processes. However, their role in neural regeneration has not been described. We found that zebrafish <i>dtx2</i>, encoding Deltex E3 ubiquitin ligase 2, is expressed in ependymo-radial glial cells in the adult spinal cord. After spinal cord injury, the heterozygous <i>dtx2</i> mutant fish motor function recovered quicker than that of the wild-type controls. The mutant fish displayed increased ependymo-radial glial cell proliferation and augmented motor neuron formation. Moreover, <i>her</i> gene expression, downstream of Notch signaling, increased in Dtx2 mutants. Notch signaling inactivation by dominant-negative Rbpj abolished the increased ependymo-radial glia proliferation caused by Dtx2 deficiency. These results indicate that ependymo-radial glial proliferation is induced by Dtx2 deficiency by activating Notch-Rbpj signaling to improve spinal cord regeneration and motor function recovery.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"540-550"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141604717","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}
{"title":"An Endothelial Cell Is Not Simply an Endothelial Cell.","authors":"Shiwani Limbu, Kara E McCloskey","doi":"10.1089/scd.2024.0088","DOIUrl":"10.1089/scd.2024.0088","url":null,"abstract":"<p><p>Endothelial cells (ECs) are a multifaceted component of the vascular system with roles in immunity, maintaining tissue fluid balance, and vascular tone. Dysregulation or dysfunction of ECs can have far-reaching implications, leading pathologies ranging from cardiovascular diseases, such as hypertension and atherosclerosis, ischemia, chronic kidney disease, blood-brain barrier integrity, dementia, and tumor metastasis. Recent advancements in regenerative medicine have highlighted the potential of stem cell-derived ECs, particularly from induced pluripotent stem cells, to treat ischemic tissues, as well as models of vascular integrity. This review summarizes what is known in the generation of ECs with an emphasis on tissue-specific ECs and EC subphenotypes important in the development of targeted cell-based therapies for patient treatment.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"517-527"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11564855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141731711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Stanniocalcin 2 Promotes Neuronal Differentiation in Neural Stem/Progenitor Cells of the Mouse Subventricular Zone Through Activation of AKT Pathway.","authors":"Zhenyu Guo, Hanyue Zhang, Xinbate Jingele, Jing Yan, Xinxiang Wang, Yingxi Liu, Tingqin Huang, Chongxiao Liu","doi":"10.1089/scd.2024.0094","DOIUrl":"10.1089/scd.2024.0094","url":null,"abstract":"<p><p>Neural stem/progenitor cells (NSPCs) persist in the mammalian subventricular zone (SVZ) throughout life, responding to various pathophysiological stimuli and playing a crucial role in central nervous system repair. Although numerous studies have elucidated the role of stanniocalcin 2 (STC2) in regulating cell differentiation processes, its specific function in NSPCs differentiation remains poorly understood. Clarifying the role of STC2 in NSPCs is essential for devising novel strategies to enhance the intrinsic potential for brain regeneration postinjury. Our study revealed the expression of STC2 in NSPCs derived from the SVZ of the C57BL/6N mouse. In cultured SVZ-derived NSPCs, STC2 treatment significantly increased the number of Tuj1 and DCX-positive cells. Furthermore, STC2 injection into the lateral ventricle promoted the neuronal differentiation of NSPCs and migration to the olfactory bulb. Conversely, the STC2 knockdown produced the opposite effect. Further investigation showed that STC2 treatment enhanced AKT phosphorylation in cultured NSPCs, whereas STC2 inhibition hindered AKT activation. Notably, the neuronal differentiation induced by STC2 was blocked by the AKT inhibitor GSK690693, whereas the AKT activator SC79 reversed the impact of STC2 knockdown on neuronal differentiation. Our findings indicate that enhancing STC2 expression in SVZ-derived NSPCs facilitates neuronal differentiation, with AKT regulation potentially serving as a key intracellular target of STC2 signaling.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"551-561"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141725429","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}
Ana Fragoso Fonseca, Rita Coelho, Mafalda Lopes- da-Silva, Luísa Lemos, Michael J Hall, Daniela Oliveira, Ana Sofia Falcão, Sandra Tenreiro, Miguel C Seabra, Pedro Antas
{"title":"Modeling Choroideremia Disease with Isogenic Induced Pluripotent Stem Cells.","authors":"Ana Fragoso Fonseca, Rita Coelho, Mafalda Lopes- da-Silva, Luísa Lemos, Michael J Hall, Daniela Oliveira, Ana Sofia Falcão, Sandra Tenreiro, Miguel C Seabra, Pedro Antas","doi":"10.1089/scd.2024.0105","DOIUrl":"10.1089/scd.2024.0105","url":null,"abstract":"<p><p>Choroideremia (CHM) is a rare X-linked chorioretinal dystrophy causing progressive vision loss due to mutations in the <i>CHM</i> gene, leading to Rab escort protein 1 loss of function. CHM disease is characterized by a progressive degeneration of the choroid, the retinal pigment epithelium (RPE), and the retina. The RPE is a monolayer of polarized cells that supports photoreceptors, providing nutrients, growth factors, and ions, and removes retinal metabolism waste products, having a central role in CHM pathogenesis. Commonly used models such as ARPE-19 cells do not reproduce accurately the nature of RPE cells. Human induced pluripotent stem cells (hiPSCs) can be differentiated into RPE cells (hiPSC-RPE), which mimic key features of native RPE, being more suited to study retinal diseases. Therefore, we took advantage of hiPSCs to generate new human-based CHM models. Two isogenic hiPSC lines were generated through CRISPR/Cas9: a CHM knock-out line from a healthy donor and a corrected CHM patient line using a knock-in approach. The differentiated hiPSC-RPE lines exhibited critical morphological and physiological characteristics of native RPE, including the presence of the tight junction markers Claudin-19 and Zonula Occludens-1, phagocytosis of photoreceptor outer segments, pigmentation, a postmitotic state, and the characteristic polygonal shape. In addition, all the studied cells were able to form retinal organoids. This work resulted in the establishment of isogenic hiPSC lines, representing a new and important CHM cellular model. To our knowledge, this is the first time that isogenic cell lines have been developed to model CHM disease, providing a valuable tool for studying the mechanisms at the onset of RPE degeneration.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"528-539"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141794457","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}