Stem cells and development最新文献

{"title":"FoxO1 Agonists Promote Bone Regeneration in Periodontitis by Protecting the Osteogenesis of Periodontal Ligament Stem Cells.","authors":"Xiaojun Huang,&nbsp;Xiaoxia Su,&nbsp;Qizhao Ma,&nbsp;Yongting Xie,&nbsp;Qiang Guo,&nbsp;Li Liao,&nbsp;Jing Zou","doi":"10.1089/scd.2023.0013","DOIUrl":"https://doi.org/10.1089/scd.2023.0013","url":null,"abstract":"<p><p>Protecting the function of periodontal ligament stem cells (PDLSCs) is crucial for bone regeneration in periodontitis. Forkhead box protein O1 (FoxO1) has been previously reported as a crucial mediator in bone homeostasis, providing a favorable environment for osteoblast proliferation and differentiation. In this study, we investigated the effect and mechanism of FoxO1 agonists on the osteogenesis of PDLSCs under inflammatory conditions. In this study, we screened FoxO1 agonists by detecting their effects on the osteogenic differentiation of PDLSCs. Then, the function of these agonists in bone regeneration was analyzed in the periodontitis model. We found that hyperoside or 2-furoyl-LIGRLO-amide trifluoroacetate salt (2-Fly) promoted osteogenic differentiation under inflammation by simultaneously inhibiting nuclear factor κB (NF-κB) activation, β-catenin expression, and reactive oxygen species (ROS) production. Moreover, local injection of hyperoside or 2-Fly rescued the expression of FoxO1 and runt-related transcription factor 2 (Runx2) in vivo, alleviating alveolar bone loss and periodontal ligament damage. These findings suggested that FoxO1 agonists exerted a protective effect on osteogenesis in PDLSCs, as a result, facilitating bone formation under inflammatory conditions. Taken together, FoxO1 might serve as a therapeutic target for bone regeneration in periodontitis by mediating multiple signaling pathways.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9972434","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":"Single-Cell Sequencing Informs That Mesenchymal Stem Cell Alleviates Renal Injury Through Regulating Kidney Regional Immunity in Lupus Nephritis.","authors":"Cheng Zhou,&nbsp;Xinlong Bai,&nbsp;Yunzhao Yang,&nbsp;Meihan Shi,&nbsp;Xueyuan Bai","doi":"10.1089/scd.2023.0047","DOIUrl":"https://doi.org/10.1089/scd.2023.0047","url":null,"abstract":"<p><p>Lupus nephritis (LN) is the common complication of systemic lupus erythematosus. The pathogenesis of LN kidney injury is unclear. In addition to systemic (extrarenal) immune cells, local (intrarenal) immune cells residing in \"kidney regional immunity\" are momentous in LN. Mesenchymal stem cell (MSC) therapy is effective for LN. However, mechanisms of MSC therapy remains unclear. In this study, we first systematically investigated the effects of MSC on immune cells in kidney regional immunity in LN using single-cell sequencing. We found that MSC reduced proinflammatory central memory CD4⁺ T cells, cytotoxic tissue-resident memory CD8⁺ T cells and exhausted CD8⁺ T cells, increased anti-inflammatory Naive/Effector CD8⁺ T cells and type 1 regulatory T cells; reduced infiltrating proinflammatory Ly6c hi/inter/lo era2⁺ macrophages, increased anti-inflammatory resident macrophage and Ly6c lo ear2^- macrophage; and reduced long-lived plasma cells and proinflammatory neutrophils and dendritic cells. This study laid a foundation for clinical applications of MSC.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10023262","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":"Progress of Bone Marrow Mesenchymal Stem Cell Mitochondrial Transfer in Organ Injury Repair.","authors":"Xuezhou Yang,&nbsp;Kaiting Ning,&nbsp;Dong-En Wang,&nbsp;Huiyun Xu","doi":"10.1089/scd.2023.0019","DOIUrl":"https://doi.org/10.1089/scd.2023.0019","url":null,"abstract":"<p><p>There has been an upsurge of interest in the bone marrow mesenchymal stem cell (BMSC) mitochondrial transfer as a potential therapeutic innovation in organ injury repair. Previous research mainly focused on its transfer routes and therapeutic effects. However, its intrinsic mechanism has not been well deciphered. The current research status needs to be summarized for the clarification of future research direction. Therefore, we review the recent significant progress in the application of BMSC mitochondrial transfer in organ injury repair. The transfer routes and effects are summarized, and some suggestions on the future research direction are provided.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9789623","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":"Pax6-Induced Proliferation and Differentiation of Bone Marrow Mesenchymal Stem Cells Into Limbal Epithelial Stem Cells.","authors":"Jie Gao,&nbsp;Ling Ding,&nbsp;Ying Xin,&nbsp;Yuandi Li,&nbsp;Keke He,&nbsp;Min Su,&nbsp;Rong Hu","doi":"10.1089/scd.2022.0249","DOIUrl":"https://doi.org/10.1089/scd.2022.0249","url":null,"abstract":"<p><p>Corneal integrity, transparency, and visual acuity are maintained by corneal epithelial cells (CECs), which are continuously renewed by limbal epithelial stem cells (LESCs). The limbal stem cell deficiency is associated with ocular diseases. This study aimed to develop a novel method to differentiate bone marrow mesenchymal stem cells (BM-MSCs) into LESC-like cells using a culture medium and paired box 6 (Pax6) transfection. The LESC-like cells were confirmed using the LESC markers CK14 and p63 and CEC marker CK12. Pax6 induces BM-MSCs to differentiate into LESC-like cells in vitro. Mouse models of chemical corneal burn were obtained and treated with the LESC-like cells. The transplantation experiment indicated that Pax6-reprogrammed BM-MSCs attached to and replenished the damaged cornea through the formation of stratified corneal epithelium. The proliferation and colony formation abilities of Pax6-overexpressing BM-MSCs were significantly enhanced. These findings provide evidence that BM-MSCs might serve as an excellent candidate for generating bioengineered corneal epithelium and provide a new strategy for the treatment of clinical corneal damage.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9794006","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":"Neurite Outgrowth and Gene Expression Profile Correlate with Efficacy of Human Induced Pluripotent Stem Cell-Derived Dopamine Neuron Grafts.","authors":"Rachel Hills, Jim A Mossman, Andres M Bratt-Leal, Ha Tran, Roy M Williams, David G Stouffer, Irina V Sokolova, Pietro P Sanna, Jeanne F Loring, Mariah J Lelos","doi":"10.1089/scd.2023.0043","DOIUrl":"10.1089/scd.2023.0043","url":null,"abstract":"<p><p>Transplantation of human induced pluripotent stem cell-derived dopaminergic (iPSC-DA) neurons is a promising therapeutic strategy for Parkinson's disease (PD). To assess optimal cell characteristics and reproducibility, we evaluated the efficacy of iPSC-DA neuron precursors from two individuals with sporadic PD by transplantation into a hemiparkinsonian rat model after differentiation for either 18 (d18) or 25 days (d25). We found similar graft size and dopamine (DA) neuron content in both groups, but only the d18 cells resulted in recovery of motor impairments. In contrast, we report that d25 grafts survived equally as well and produced grafts rich in tyrosine hydroxylase-positive neurons, but were incapable of alleviating any motor deficits. We identified the mechanism of action as the extent of neurite outgrowth into the host brain, with d18 grafts supporting significantly more neurite outgrowth than nonfunctional d25 grafts. RNAseq analysis of the cell preparation suggests that graft efficacy may be enhanced by repression of differentiation-associated genes by REST, defining the optimal predifferentiation state for transplantation. This study demonstrates for the first time that DA neuron grafts can survive well in vivo while completely lacking the capacity to induce recovery from motor dysfunction. In contrast to other recent studies, we demonstrate that neurite outgrowth is the key factor determining graft efficacy and our gene expression profiling revealed characteristics of the cells that may predict their efficacy. These data have implication for the generation of DA neuron grafts for clinical application.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10398740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9991729","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":"In Vitro Transdifferentiation Potential of Equine Mesenchymal Stem Cells into Schwann-Like Cells.","authors":"Lucas Vinícius de Oliveira Ferreira,&nbsp;Beatriz da Costa Kamura,&nbsp;João Pedro Marmol de Oliveira,&nbsp;Natielly Dias Chimenes,&nbsp;Marcio de Carvalho,&nbsp;Leandro Alves Dos Santos,&nbsp;Luciane Alarcão Dias-Melicio,&nbsp;Renée Laufer Amorim,&nbsp;Rogerio Martins Amorim","doi":"10.1089/scd.2022.0274","DOIUrl":"https://doi.org/10.1089/scd.2022.0274","url":null,"abstract":"<p><p>Schwann cells (SCs) are essential for the regenerative processes of peripheral nerve injuries. However, their use in cell therapy is limited. In this context, several studies have demonstrated the ability of mesenchymal stem cells (MSCs) to transdifferentiate into Schwann-like cells (SLCs) using chemical protocols or co-culture with SCs. Here, we describe for the first time the in vitro transdifferentiation potential of MSCs derived from equine adipose tissue (AT) and equine bone marrow (BM) into SLCs using a practical method. In this study, the facial nerve of a horse was collected, cut into fragments, and incubated in cell culture medium for 48 h. This medium was used to transdifferentiate the MSCs into SLCs. Equine AT-MSCs and BM-MSCs were incubated with the induction medium for 5 days. After this period, the morphology, cell viability, metabolic activity, gene expression of glial markers glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), p75 and S100β, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and glial cell-derived neurotrophic factor (GDNF), and the protein expression of S100 and GFAP were evaluated in undifferentiated and differentiated cells. The MSCs from the two sources incubated with the induction medium exhibited similar morphology to the SCs and maintained cell viability and metabolic activity. There was a significant increase in the gene expression of BDNF, GDNF, GFAP, MBP, p75, and S100β in equine AT-MSCs and GDNF, GFAP, MBP, p75, and S100β in equine BM-MSCs post-differentiation. Immunofluorescence analysis revealed GFAP expression in undifferentiated and differentiated cells, with a significant increase in the integrated pixel density in differentiated cells and S100 was only expressed in differentiated cells from both sources. These findings indicate that equine AT-MSCs and BM-MSCs have great transdifferentiation potential into SLCs using this method, and they represent a promising strategy for cell-based therapy for peripheral nerve regeneration in horses.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10401561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10009805","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":"Genetically Modified Mesenchymal Stromal Cells in Cartilage Regeneration.","authors":"Yujun Sun,&nbsp;Chunyu Xue,&nbsp;Haoyu Wu,&nbsp;Changchuan Li,&nbsp;Shixun Li,&nbsp;Jiankai Luo,&nbsp;Taihe Liu,&nbsp;Yue Ding","doi":"10.1089/scd.2022.0242","DOIUrl":"https://doi.org/10.1089/scd.2022.0242","url":null,"abstract":"<p><p>Articular cartilage injury is common in various conditions, including osteoarthritis, rheumatic diseases, and trauma. Current treatments for cartilage injury fail to completely regenerate the damaged cartilage. Mesenchymal stromal cells (MSCs) have emerged as potential candidates for cartilage regeneration. However, MSCs exhibit hypertrophic differentiation, and their chondrogenic ability is reduced in an inflammatory environment. In recent years, genetic modification has been proposed for optimizing MSC-based therapies, some of which are expected to enter clinical trials. This review summarizes recent research findings and developments in genetic engineering strategies to enhance stem cell-based therapy for cartilage regeneration. We also discuss the mechanisms of biofunctions of MSCs in cartilage regeneration and outline the efficacy and safety of the different genetic modification strategies, including viral and nonviral delivery transduction. Finally, we highlight the major challenges and prospects for clinical translation of genetically modified MSCs.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9781025","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":"KDM6A-Mediated Regulation of Cranial Frontal Bone Suture Fusion in Mice Is Sex Dependent.","authors":"Clara Pribadi,&nbsp;Dimitrios Cakouros,&nbsp;Esther Camp,&nbsp;Peter Anderson,&nbsp;Stan Gronthos","doi":"10.1089/scd.2023.0022","DOIUrl":"https://doi.org/10.1089/scd.2023.0022","url":null,"abstract":"<p><p>The five flat bones of developing cranial plates are bounded by fibrous sutures, which remain open during development to accommodate for the growing brain. Kdm6A is a demethylase that removes the epigenetic repressive mark, trimethylated lysine 27 on histone 3 (H3K27me3), from the promoters of osteogenic genes, and has previously been reported to promote osteogenesis in cranial bone cells. This study generated a mesenchyme-specific deletion of a histone demethylase, <i>Kdm6a</i>, to assess the effects of <i>Kdm6a</i> loss, in cranial plate development and suture fusion. The results showed that the loss of <i>Kdm6a</i> in <i>Prx1⁺</i> cranial cells caused increased anterior width and length in the calvaria of both male and female mice. However, the posterior length was further decreased in female mice. Moreover, loss of <i>Kdm6a</i> resulted in suppression of late suture development and calvarial frontal bone formation predominantly in female mice. In vitro assessment of calvaria cultures isolated from female <i>Kdm6a</i> knockout mice found significantly suppressed calvarial osteogenic differentiation potential, associated with decreased gene expression levels of <i>Runx2</i> and <i>Alkaline Phosphatase</i> and increased levels of the suppressive mark, H3K27me3, on the respective gene promoters. Conversely, cultured calvaria bone cultures isolated from male <i>Kdm6a</i> knockout mice exhibited an increased osteogenic differentiation potential. Interestingly, the milder effects on cranial suture development in <i>Kdm6a</i> knockout male mice, were associated with an overcompensation of the <i>Kdm6a</i> Y-homolog, <i>Kdm6c</i>, and increased expression levels of <i>Kdm6b</i> in calvarial bone cultures. Taken together, these data demonstrate a role for <i>Kdm6a</i> during calvarial development and patterning, predominantly in female mice, and highlight the potential role of Kdm6 family members in patients with unexplained craniofacial deformities.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9845088","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":"mTORC1-Induced Bone Marrow-Derived Mesenchymal Stem Cell Exhaustion Contributes to the Bone Abnormalities in <i>Klotho</i>-Deficient Mice of Premature Aging.","authors":"Ran Feng,&nbsp;Su Wu,&nbsp;Ruofei Li,&nbsp;Kunling Huang,&nbsp;Ting Zeng,&nbsp;Zhifen Zhou,&nbsp;Xiaoqin Zhong,&nbsp;Zhou Songyang,&nbsp;Feng Liu","doi":"10.1089/scd.2022.0243","DOIUrl":"https://doi.org/10.1089/scd.2022.0243","url":null,"abstract":"<p><p>Stem cell exhaustion is a hallmark of aging. <i>Klotho</i>-deficient mice (<i>kl/kl</i> mice) is a murine model that mimics human aging with significant bone abnormalities. The aim of this study is using <i>kl/kl</i> mice to investigate the functional change of bone marrow-derived mesenchymal stem cells (BMSCs) and explore the underlying mechanism. We found that <i>klotho</i> deficiency leads to bone abnormalities. In addition, <i>kl/kl</i> BMSCs manifested hyperactive proliferation but functionally declined both in vivo and in vitro. Mammalian target of rapamycin complex 1 (mTORC1) activity was higher in freshly isolated <i>kl/kl</i> BMSCs, and autophagy in <i>kl/kl</i> BMSCs was significantly decreased, possibly through mTORC1 activation. Conditional medium containing soluble Klotho protein (sKL) rescued hyperproliferation of <i>kl/kl</i> BMSCs by inhibiting mTORC1 activity and restoring autophagy. Finally, intraperitoneal injection of mTORC1 inhibitor rapamycin restored BMSC quiescence, ameliorated bone phenotype, and increased life span of <i>kl/kl</i> mice in vivo. This research highlights a therapeutic strategy to maintain the homeostasis of adult stem cell pool for healthy bone aging.</p>","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9960910","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> Detection, Characterization, and Spontaneous Differentiation In Vitro of Very Small Embryonic-Like Putative Stem Cells in Adult Mammalian Ovary (10.1089/scd.2010.0461).","authors":"","doi":"10.1089/scd.2010.0461.retract","DOIUrl":"https://doi.org/10.1089/scd.2010.0461.retract","url":null,"abstract":"","PeriodicalId":21934,"journal":{"name":"Stem cells and development","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278013/pdf/scd.2010.0461.retract.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9665192","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}