IF 4 2区医学

STEM CELLS Pub Date : 2025-02-17 DOI: 10.1093/stmcls/sxaf008

Ziqian Wang, Xianni Yang, Haopeng Yu, Songsong Zhu, Ruiye Bi

{"title":"Single-cell transcriptome sequencing in synovial joint: insights of new progenitors and targets in joint development and disease.","authors":"Ziqian Wang, Xianni Yang, Haopeng Yu, Songsong Zhu, Ruiye Bi","doi":"10.1093/stmcls/sxaf008","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf008","url":null,"abstract":"Synovial joints, such as knee, temporomandibular, and spinal joints, play a key role in human movement and postural maintenance. Biological research has focused on understanding their developmental process and disease mechanisms. In recent years, the rapid development of single-cell transcriptome sequencing has provided a powerful tool for revealing the mysteries of synovial joints. Single-cell transcriptome sequencing can accurately capture the gene expression profile of each cell, thereby revealing the heterogeneity and interactions of different cell types in synovial joints. During joint development, this technique contributes to elucidating the molecular mechanisms of joint formation, cartilage differentiation, and synovial tissue construction. In terms of joint disease research, single-cell sequencing technology has been applied to the molecular pathology studies of various joint diseases such as osteoarthritis, rheumatoid arthritis, and intervertebral disk degeneration, providing new perspectives and strategies for early diagnosis, accurate treatment, and prognosis assessment of diseases.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Raman Spectroscopies for Cancer Research and Clinical Applications: a Focus on Cancer Stem Cells.

IF 4 2区医学

STEM CELLS Pub Date : 2025-02-14 DOI: 10.1093/stmcls/sxae084

Francesca Pagliari, Luca Tirinato, Enzo Di Fabrizio

{"title":"Raman Spectroscopies for Cancer Research and Clinical Applications: a Focus on Cancer Stem Cells.","authors":"Francesca Pagliari, Luca Tirinato, Enzo Di Fabrizio","doi":"10.1093/stmcls/sxae084","DOIUrl":"https://doi.org/10.1093/stmcls/sxae084","url":null,"abstract":"Over the last two decades, research has increasingly focused on Cancer Stem Cells (CSCs), considered responsible for tumor formation, resistance to therapies, and relapse. The traditional \"static\" CSC model used to describe tumor heterogeneity has been challenged by the evidence of CSC dynamic nature and plasticity. A comprehensive understanding of the mechanisms underlying this plasticity, and the capacity to unambiguously identify cancer markers to precisely target CSCs are crucial aspects for advancing cancer research and introducing more effective treatment strategies. In this context, Raman spectroscopy (RS) and specific Raman schemes, including CARS, SRS, SERS, have emerged as innovative tools for molecular analyses both in vitro and in vivo. In fact, these techniques have demonstrated considerable potential in the field of cancer detection, as well as in intraoperative settings, thanks to their label-free nature and minimal invasiveness. However, the RS integration in pre-clinical and clinical applications, particularly in the CSC field, remains limited. This review provides a concise overview of the historical development of RS and its advantages. Then, after introducing the CSC features and the challenges in targeting them with traditional methods, we review and discuss the current literature about the application of RS for revealing and characterizing CSCs and their inherent plasticity, including a brief paragraph about the integration of artificial intelligence with RS. By providing the possibility to better characterize the cellular diversity in their microenvironment, RS could revolutionize current diagnostic and therapeutic approaches, enabling early identification of CSCs and facilitating the development of personalized treatment strategies.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Extracellular microvesicles/exosomes - magic bullets in horizontal transfer between cells of mitochondria and molecules regulating mitochondria activity.

IF 4 2区医学

STEM CELLS Pub Date : 2025-02-14 DOI: 10.1093/stmcls/sxae086

Mariusz Z Ratajczak, Kannathasan Thetchinamoorthy, Diana Wierzbicka, Adrian Konopko, Janina Ratajczak, Magdalena Kucia

{"title":"Extracellular microvesicles/exosomes - magic bullets in horizontal transfer between cells of mitochondria and molecules regulating mitochondria activity.","authors":"Mariusz Z Ratajczak, Kannathasan Thetchinamoorthy, Diana Wierzbicka, Adrian Konopko, Janina Ratajczak, Magdalena Kucia","doi":"10.1093/stmcls/sxae086","DOIUrl":"https://doi.org/10.1093/stmcls/sxae086","url":null,"abstract":"Extracellular microvesicles (ExMVs) were one of the first communication platforms between cells that emerged early in evolution. Evidence indicates that all types of cells secrete these small circular structures surrounded by a lipid membrane that plays an important role in cellular physiology and some pathological processes. ExMVs interact with target cells and may stimulate them by ligands expressed on their surface and/or transfer to the target cells their cargo comprising various RNA species, proteins, bioactive lipids, and signaling nucleotides. These small vesicles can also hijack some organelles from the cells and, in particular, transfer mitochondria, which are currently the focus of scientific interest for their potential application in clinical settings. Different mechanisms exist for transferring mitochondria between cells, including their encapsulation in ExMVs or their uptake in a \"naked\" form. It has also been demonstrated that mitochondria transfer may involve direct cell-cell connections by signaling nanotubules. In addition, evidence accumulated that ExMVs could be enriched for regulatory molecules, including some miRNA species and proteins that regulate the function of mitochondria in the target cells. Recently, a new beneficial effect of mitochondrial transfer has been reported based on inducing the mitophagy process, removing damaged mitochondria in the recipient cells to improve their energetic state. Based on this novel role of ExMVs in powering the energetic state of target cells, we present a current point of view on this topic and review some selected most recent discoveries and recently published most relevant papers.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Enrichment of spermatogonial stem cells and staging of the testis cycle in a dasyurid marsupial, the fat-tailed dunnart.

IF 4 2区医学

STEM CELLS Pub Date : 2025-02-13 DOI: 10.1093/stmcls/sxaf007

Gerard A Tarulli, Patrick R S Tatt, Rhys Howlett, Sara Ord, Stephen R Frankenberg, Andrew J Pask

{"title":"Enrichment of spermatogonial stem cells and staging of the testis cycle in a dasyurid marsupial, the fat-tailed dunnart.","authors":"Gerard A Tarulli, Patrick R S Tatt, Rhys Howlett, Sara Ord, Stephen R Frankenberg, Andrew J Pask","doi":"10.1093/stmcls/sxaf007","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf007","url":null,"abstract":"There is increasing interest in use of marsupial models in research, for use in next-generation conservation by improving fitness through genetic modification, and in de-extinction efforts. Specifically this includes dasyurid marsupials such as the Thylacine, Tasmanian devil, quolls and the small rodent-like dunnarts. Technologies for generating genetically modified Australian marsupials remains to be established. Given the need to advance research in this space, the fat-tailed dunnart (Sminthopsis crassicaudata) is being established as a model for marsupial spermatogonial stem cell isolation, modification and testicular transplantation. This species is small (60-90mm body size), polyovulatory (8-12 pups per birth), and can breed in standard rodent facilities when housed in a 12:12 light cycle. To develop the fat tailed dunnart as a model for next-generation marsupial conservation, this study aimed to enrich dunnart spermatogonial stem cells from whole testis digestions using a fluorescent dye technology and fluorescence-activated cell sorting. This approach is not dependent on antibodies or genetic reporter animals that are limiting factors when performing cell sorting on species separated from human and mouse by large evolutionary timescales. This study also assessed development of spermatogonia and spermatogenesis in the fat-tailed dunnart, by making the first definition of the cycle of the seminiferous epithelium in any dasyurid. Overall, this is the first detailed study to assess the cycle of dasyurid spermatogenesis and provides a valuable method to enrich marsupial spermatogonial stem cells for cellular, functional and molecular analysis.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Harnessing the diversity and potential of endogenous skeletal stem cells for musculoskeletal tissue regeneration.

IF 4 2区医学

STEM CELLS Pub Date : 2025-02-13 DOI: 10.1093/stmcls/sxaf006

Kelly C Weldon, Michael T Longaker, Thomas H Ambrosi

{"title":"Harnessing the diversity and potential of endogenous skeletal stem cells for musculoskeletal tissue regeneration.","authors":"Kelly C Weldon, Michael T Longaker, Thomas H Ambrosi","doi":"10.1093/stmcls/sxaf006","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf006","url":null,"abstract":"In our aging society, the degeneration of the musculoskeletal system and adjacent tissues is a growing orthopedic concern. As bones age, they become more fragile, increasing the risk of fractures and injuries. Furthermore, tissues like cartilage accumulate damage, leading to widespread joint issues. Compounding this, the regenerative capacity of these tissues declines with age, exacerbating the consequences of fractures and cartilage deterioration. With rising demand for fracture and cartilage repair, bone-derived stem cells have attracted significant research interest. However, the therapeutic use of stem cells has produced inconsistent results, largely due to ongoing debates and uncertainties regarding the precise identity of the stem cells responsible for musculoskeletal growth, maintenance and repair. This review focuses on the potential to leverage endogenous skeletal stem cells (SSCs)-a well-defined population of stem cells with specific markers, reliable isolation techniques, and functional properties-in bone repair and cartilage regeneration. Understanding SSC behavior in response to injury, including their activation to a functional state, could provide insights into improving treatment outcomes. Techniques like microfracture surgery, which aim to stimulate SSC activity for cartilage repair, are of particular interest. Here, we explore the latest advances in how such interventions may modulate SSC function to enhance bone healing and cartilage regeneration.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Senescence accelerated mouse-prone 8: a model of neuroinflammation and aging with features of sporadic Alzheimer's disease. 衰老加速小鼠：具有散发性阿尔茨海默病特征的神经炎症和衰老模型。

IF 4 2区医学

STEM CELLS Pub Date : 2025-02-12 DOI: 10.1093/stmcls/sxae091

Jun Ong, Kazunori Sasaki, Farhana Ferdousi, Megalakshmi Suresh, Hiroko Isoda, Francis G Szele

{"title":"Senescence accelerated mouse-prone 8: a model of neuroinflammation and aging with features of sporadic Alzheimer's disease.","authors":"Jun Ong, Kazunori Sasaki, Farhana Ferdousi, Megalakshmi Suresh, Hiroko Isoda, Francis G Szele","doi":"10.1093/stmcls/sxae091","DOIUrl":"10.1093/stmcls/sxae091","url":null,"abstract":"The large majority of Alzheimer's disease (AD) cases are sporadic with unknown genetic causes. In contrast, only a small percentage of AD cases are familial, with known genetic causes. Paradoxically, there are only few validated mouse models of sporadic AD but many of familial AD. Senescence accelerated mouse-prone 8 (SAMP8) mice are a model of accelerated aging with features of sporadic AD. They exhibit a more complete suite of human AD-relevant pathologies than most familial models. SAMP8 brains are characterized by inflammation, glial activation, b-amyloid deposits, and hyperphosphorylated Tau. The excess amyloid deposits congregate around blood vessels leading to vascular impairment and leaky BBBs in these mice. SAMP8 mice also exhibit neuronal cell death, a feature not typically seen in models of familial AD. Additionally, adult hippocampal neurogenesis is decreased in SAMP8 mice and correspondingly, they have reduced cognitive ability. In line with this, hippocampal LTP is significantly compromised in SAMP8 mice. No model is perfect and SAMP8 mice are limited by the lack of clarity about their genomic differences from control Senescence Accelerated Mouse-Resistant 1 (SAMR1) mice although their transcriptomics changes are being revealed. To further complicate matters, multiple substrains of SAMP8 mice have emerged over the years, sometimes making comparisons of studies difficult. Despite these challenges, we argue that SAMP8 mice can be useful for studying AD-relevant symptoms and propose important experiments to strengthen this already useful model.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11816274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142997164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

A Serum- and Feeder-Free System to Generate CD4 and Regulatory T Cells from Human iPSCs.

IF 4 2区医学

STEM CELLS Pub Date : 2025-01-29 DOI: 10.1093/stmcls/sxaf001

Helen Fong, Matthew Mendel, John Jascur, Laeya Najmi, Ken Kim, Garrett Lew, Swetha Garimalla, Suruchi Schock, Jing Hu, Andres Gordillo Villegas, Anthony Conway, Jason D Fontenot, Simona Zompi

{"title":"A Serum- and Feeder-Free System to Generate CD4 and Regulatory T Cells from Human iPSCs.","authors":"Helen Fong, Matthew Mendel, John Jascur, Laeya Najmi, Ken Kim, Garrett Lew, Swetha Garimalla, Suruchi Schock, Jing Hu, Andres Gordillo Villegas, Anthony Conway, Jason D Fontenot, Simona Zompi","doi":"10.1093/stmcls/sxaf001","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf001","url":null,"abstract":"iPSCs can serve as a renewable source of a consistent edited cell product, overcoming limitations of primary cells. While feeder-free generation of clinical grade iPSC-derived CD8 T cells has been achieved, differentiation of iPSC-derived CD4sp and regulatory T cells requires mouse stromal cells in an artificial thymic organoid. Here we report a serum- and feeder-free differentiation process suitable for large-scale production. Using an optimized concentration of PMA/Ionomycin, we generated iPSC-CD4sp T cells at high efficiency and converted them to Tregs using TGFβ and ATRA. Using genetic engineering, we demonstrated high, non-viral, targeted integration of an HLA-A2 CAR in iPSCs. iPSC-Tregs +/- HLA-A2-targeted CAR phenotypically, transcriptionally and functionally resemble primary Tregs and suppress T cell proliferation in vitro. Our work is the first to demonstrate an iPSC-based platform amenable to manufacturing CD4 T cells to complement iPSC-CD8 oncology products and functional iPSC-Tregs to deliver Treg cell therapies at scale.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Efficient and Rapid Generation of Neural Stem Cells by Direct Conversion Fibroblasts with Single microRNAs.

IF 4 2区医学

STEM CELLS Pub Date : 2025-01-25 DOI: 10.1093/stmcls/sxaf003

Yuanyuan Li, Jing Sun, Tingting Xu, Bo Dai, Yuesi Wang

引用次数: 0

Adult Human Heart ECM Improves Human iPSC-CM Function via Mitochondrial and Metabolic Maturation.

IF 4 2区医学

STEM CELLS Pub Date : 2025-01-25 DOI: 10.1093/stmcls/sxaf005

S Gulberk Ozcebe, Mateo Tristan, Pinar Zorlutuna

{"title":"Adult Human Heart ECM Improves Human iPSC-CM Function via Mitochondrial and Metabolic Maturation.","authors":"S Gulberk Ozcebe, Mateo Tristan, Pinar Zorlutuna","doi":"10.1093/stmcls/sxaf005","DOIUrl":"10.1093/stmcls/sxaf005","url":null,"abstract":"Myocardial infarction can lead to the loss of billions of cardiomyocytes, and while cell-based therapies are an option, immature nature of in vitro-generated human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iCMs) is a roadblock to their development. Existing iPSC differentiation protocols don't go beyond producing fetal iCMs. Recently, adult extracellular matrix (ECM) was shown to retain tissue memory and have some success driving tissue-specific differentiation in unspecified cells in various organ systems. Therefore, we focused on investigating the effect of adult human heart-derived ECM on iPSC cardiac differentiation and subsequent maturation. By preconditioning iPSCs with ECM, we tested whether creating cardiac environments around iPSCs would drive iPSCs toward cardiac fate and which ECM components might be involved. We report novel high- and low- abundance proteomes of young, adult, and aged human hearts, with relative abundances to total proteins and each other. We found that adult ECM had extracellular galactin-1, fibronectin, fibrillins, and perlecan (HSPG2) which are implicated in normal heart development. We also showed preconditioning iPSCs with adult cardiac ECM resulted in enhanced cardiac differentiation, yielding iCMs with higher functional maturity, more developed mitochondrial network and coverage, enhanced metabolic maturity, and shift towards more energetic profile. These findings demonstrate the potential use of cardiac ECM in iCM maturation and as a promising strategy for developing iCM-based therapies, disease modeling, and drug screening studies. Upon manipulating ECM, we concluded that the beneficial effects observed were not solely due to the ECM proteins, which might be related to the decorative units attached.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143035483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Decoding the Epigenetic and Transcriptional Basis of Direct Cardiac Reprogramming.

IF 4 2区医学

STEM CELLS Pub Date : 2025-01-24 DOI: 10.1093/stmcls/sxaf002

William G Peng, Anteneh Getachew, Yang Zhou

引用次数: 0

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