IF 4 2区医学

STEM CELLS Pub Date : 2025-06-11 DOI: 10.1093/stmcls/sxae081

Jiling Qiu, Yifan Zhao, Yingyi Chen, Yanxue Wang, Juan Du, Junji Xu, Lijia Guo, Yi Liu

{"title":"Exosomes derived from bone marrow-derived mesenchymal stem cells of exercise-trained mice improve wound healing by inhibiting macrophage M1 polarization.","authors":"Jiling Qiu, Yifan Zhao, Yingyi Chen, Yanxue Wang, Juan Du, Junji Xu, Lijia Guo, Yi Liu","doi":"10.1093/stmcls/sxae081","DOIUrl":"https://doi.org/10.1093/stmcls/sxae081","url":null,"abstract":"Background: Engaging in appropriate exercise is advantageous for our well-being. We investigated whether exercise could affect the paracrine function of BMSCs and whether exosomes derived from treadmill exercise-trained mouse (Exo-tread) BMSCs could engender more pronounced effects on wound healing.Methods: Firstly, the effects of treadmill exercise on mouse BMSCs biological functions, exosomes secretion quantity and identification were assessed. Furthermore, we assessed the effects of Exo-tread on M1 macrophage by qPCR and FCM in vitro. Additionally, the expressions and phosphorylation status of p65 and p38 proteins were analyzed via Western blotting. For the in vivo component, we induced wound models of mice. Subsequently, we assessed the effects of Exo-tread using various methodologies including imaging, H&E, Masson, immunohistochemical, and immunofluorescence staining. To demonstrate whether Exo-tread could act through macrophages, we further depleted mouse macrophages.Results: Exercise accelerated the proliferation of BMSCs and the secretion of exosomes. In vitro, Exo-tread markedly decreased the expression of inflammatory factors, while concurrently suppressing M1 polarization in mouse peritoneal macrophages compared to the Exo-ctrl group. These observed effects were potentially mediated by the reduction in the M1 polarization ratio, achieved through the inhibition of p65 and p38 phosphorylation. Similarly, in vivo experiments demonstrated that Exo-tread significantly enhanced wound healing by attenuating inflammatory cytokines and M1 macrophages.Conclusions: Exo-tread facilitates wound healing by mitigating the inflammatory response, achieved through a reduction in the M1 polarization ratio.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264978","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

Contribution of cytokeratin 19-expressing cells towards islet regeneration induced by multipotent stromal cell secreted proteins. 表达细胞角蛋白19的细胞对多能基质细胞分泌蛋白诱导胰岛再生的贡献。

IF 4 2区医学

STEM CELLS Pub Date : 2025-06-10 DOI: 10.1093/stmcls/sxaf036

Nazihah Rasiwala, Gillian I Bell, Anargyros Xenocostas, David A Hess

{"title":"Contribution of cytokeratin 19-expressing cells towards islet regeneration induced by multipotent stromal cell secreted proteins.","authors":"Nazihah Rasiwala, Gillian I Bell, Anargyros Xenocostas, David A Hess","doi":"10.1093/stmcls/sxaf036","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf036","url":null,"abstract":"Residual beta cell function has been documented in 'medalist' patients that have lived with Type 1 diabetes (T1D) for >50 years. In addition, endocrine cell neogenesis first occurs in the developing human embryo from a progenitor cells derived from pancreatic ductal epithelial structure. Thus, beta cell conversion from a dormant epithelial precursor remains a promising approach to regenerate islets during T1D. We have previously shown that intra-pancreatic (iPan) injection of Wnt pathway-stimulated conditioned media (Wnt+ CdM) generated from human bone marrow-derived multipotent stromal cells (MSC) contained islet regenerative factors that reduced hyperglycemia and recovered beta cell mass in streptozotocin-treated mice. However, the endogenous source of regenerated beta cells remains unknown. Herein, we employed cytokeratin 19 (CK19)-CreERT Rosa26-mTomato lineage-tracing mice to assess endocrine conversion of CK19+ cells during MSC CdM-induced islet regeneration. Mice iPan-injected with Wnt+ CdM demonstrated reduced blood glucose levels and improved glucose tolerance compared to mice injected with unconditioned basal media. CdM-injected mice also showed increased islet number and beta cell mass, as well as CK19+ cells within regenerating islets. The frequency of insulin+ cells that co-expressed tdTomato within dissociated pancreas samples observed via flow cytometry was 5-fold higher in Wnt+ CdM-injected mice (~5%) compared to basal media-injected controls (~1%). Collectively, in vivo lineage tracing revealed conversion of CK19+ cells to functional beta cells partially contributed to islet regeneration induced by Wnt activated MSC CdM. Future studies are required to delineate alternate cell types and mechanisms participating in islet regeneration induced by direct delivery of MSC-CdM.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144256928","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

Neural stem cell-derived extracellular vesicles alleviate inflammatory responses in a mouse model of atopic dermatitis. 神经干细胞来源的细胞外囊泡减轻了特应性皮炎小鼠模型的炎症反应。

IF 4 2区医学

STEM CELLS Pub Date : 2025-05-30 DOI: 10.1093/stmcls/sxaf034

Seulbee Lee, Donghun Hyun, Yong Namkung, Boram Park, Byounggwan Lee, Junhyung Myung, Sunghoi Hong

{"title":"Neural stem cell-derived extracellular vesicles alleviate inflammatory responses in a mouse model of atopic dermatitis.","authors":"Seulbee Lee, Donghun Hyun, Yong Namkung, Boram Park, Byounggwan Lee, Junhyung Myung, Sunghoi Hong","doi":"10.1093/stmcls/sxaf034","DOIUrl":"https://doi.org/10.1093/stmcls/sxaf034","url":null,"abstract":"Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by disrupted epidermal barrier function and excessive immune activation. Conventional treatments using corticosteroids and immunosuppressants provide only temporary relief and often induce adverse side effects, highlighting the need for novel, effective therapy. In this study, we investigated the therapeutic potential of neural stem cell-extracellular vesicles (NSC-EVs) derived from NSC-conditioned medium (NSC-CM) in modulating inflammatory responses in AD. In vitro experiments using human keratinocytes (HaCaT) and murine macrophages (RAW264.7) showed that both NSC-CM and NSC-EVs can significantly decrease the expression of pro-inflammatory cytokines and chemokines, inhibit the phosphorylation of NF-κB, and reduce inducible nitric oxide synthase (iNOS). In addition, topical application of NSC-CM and NSC-EVs alleviated atopic symptoms, reduced mast cell infiltration, and improved skin barrier integrity in a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model. Proteomic analysis identified key proteins related to immune regulation and extracellular matrix remodeling in NSC-EVs, indicating their active role in mitigating inflammation and tissue repair. Altogether, our results demonstrated the potent anti-inflammatory effects of NSC-EVs, highlighting their potential to be a novel and effective therapeutic option for AD and other inflammation-related diseases.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144179789","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

SARS-CoV2 infection triggers inflammatory conditions and astrogliosis-related gene expression in long-term human cortical organoids. SARS-CoV2感染在长期的人类皮质类器官中引发炎症条件和星形胶质相关基因表达。

IF 4 2区医学

STEM CELLS Pub Date : 2025-05-27 DOI: 10.1093/stmcls/sxaf010

Mathilde Colinet, Ioana Chiver, Antonela Bonafina, Gérald Masset, Daniel Almansa, Emmanuel Di Valentin, Jean-Claude Twizere, Laurent Nguyen, Ira Espuny-Camacho

{"title":"SARS-CoV2 infection triggers inflammatory conditions and astrogliosis-related gene expression in long-term human cortical organoids.","authors":"Mathilde Colinet, Ioana Chiver, Antonela Bonafina, Gérald Masset, Daniel Almansa, Emmanuel Di Valentin, Jean-Claude Twizere, Laurent Nguyen, Ira Espuny-Camacho","doi":"10.1093/stmcls/sxaf010","DOIUrl":"10.1093/stmcls/sxaf010","url":null,"abstract":"SARS-CoV2, severe acute respiratory syndrome coronavirus 2, is frequently associated with neurological manifestations. Despite the presence of mild to severe CNS-related symptoms in a cohort of patients, there is no consensus whether the virus can infect directly brain tissue or if the symptoms in patients are a consequence of peripheral infectivity of the virus. Here, we use long-term human stem cell-derived cortical organoids to assess SARS-CoV2 infectivity of brain cells and unravel the cell-type tropism and its downstream pathological effects. Our results show consistent and reproducible low levels of SARS-CoV2 infection of astrocytes, deep projection neurons, upper callosal neurons, and inhibitory neurons in 6 months of human cortical organoids. Interestingly, astrocytes showed the highest infection rate among all infected cell populations which led to changes in their morphology and upregulation of SERPINA3, CD44, and S100A10 astrogliosis markers. Further, transcriptomic analysis revealed overall changes in expression of genes related to cell metabolism, astrogliosis and, inflammation and further, upregulation of cell survival pathways. Thus, local and minor infectivity of SARS-CoV2 in the brain may induce widespread adverse effects and lead to the resilience of dysregulated neurons and astrocytes within an inflammatory environment.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12121356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655708","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

Unlocking the potential of regionally activated injury/ischemia-induced stem cells for neural regeneration. 释放区域激活损伤/缺血诱导干细胞用于神经再生的潜力。

IF 4 2区医学

STEM CELLS Pub Date : 2025-05-27 DOI: 10.1093/stmcls/sxaf015

Takayuki Nakagomi

{"title":"Unlocking the potential of regionally activated injury/ischemia-induced stem cells for neural regeneration.","authors":"Takayuki Nakagomi","doi":"10.1093/stmcls/sxaf015","DOIUrl":"10.1093/stmcls/sxaf015","url":null,"abstract":"In the past, the mammal central nervous system (CNS) was assumed to lack the capacity for neural repair. However, increasing evidence shows that the CNS has repair capacity after injury. The migratory capacity of neural stem/progenitor cells (NSPCs) from subventricular zones (SVZ) is limited, and the precise repair mechanism active after ischemic stroke remains unknown. Consequently, it remains unclear how neural regeneration occurs in regions far from the SVZ, such as the cortex, especially given that these NSPCs can only migrate toward ischemic areas within specific brain regions. Nonetheless, using a mouse model of ischemic stroke with ischemic areas limited to the ipsilateral side of the cortex, we previously identified regionally-derived stem cells, injury/ischemia-induced stem cells (iSCs), within poststroke areas. Moreover, we showed that iSCs, which had the potential to differentiate into electrophysiologically functional neurons, were present within ischemic areas in poststroke human brains. This indicates that ischemic insult can activate locally-derived stem cells, even in nonneurogenic zones, and that iSCs can help achieve neural regeneration after ischemic stroke. However, inflammatory cells typically fill ischemic areas impairing neural regeneration in these areas. Here, we present the origin, characterization, and roles of iSCs based on our recent research. In addition, we discussed the potential of iSC-based therapies to achieve neural regeneration after ischemic stroke.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762665","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

MSC-derived exosomal miR-125b-5p suppressed retinal microvascular endothelial cell ferroptosis in diabetic retinopathy. msc来源的外泌体miR-125b-5p抑制糖尿病视网膜病变视网膜微血管内皮细胞铁下垂。

IF 4 2区医学

STEM CELLS Pub Date : 2025-05-27 DOI: 10.1093/stmcls/sxaf023

Jun Tong, Yueqin Chen, Xinru Ling, Zhenping Huang, Genhong Yao, Zhenggao Xie

{"title":"MSC-derived exosomal miR-125b-5p suppressed retinal microvascular endothelial cell ferroptosis in diabetic retinopathy.","authors":"Jun Tong, Yueqin Chen, Xinru Ling, Zhenping Huang, Genhong Yao, Zhenggao Xie","doi":"10.1093/stmcls/sxaf023","DOIUrl":"10.1093/stmcls/sxaf023","url":null,"abstract":"Progressive endothelial cell injury of retinal vascular is a vital factor in diabetic retinopathy (DR) pathogenesis. Mesenchymal stem cells-derived small extracellular vesicles (MSC-sEVs) showed beneficial effects on DR. However, the effects of MSC-sEVs on endothelial dysfunction of DR and the mechanism is still unclear. In this study, MSC-sEVs mitigated retinal blood-retina barrier (BRB) impairment in rats with streptozotocin (STZ)-induced DR by reducing ferroptosis in vivo and in vitro. MSC-sEVs miRNA sequencing analysis revealed that miR-125b-5p may mediate human retina microvascular endothelial cells (HRMECs) ferroptosis and P53 as a downstream target based on dual-luciferase reporter assays. Silencing miR-125b-5p in MSC-sEVs reversed the therapeutic effects of MSC-sEVs on rats with DR and advanced glycation end products (AGEs)-treated HRMECs. Additionally, overexpression of miR-125b-5p could diminish ferroptosis in HRMECs, and this effect could be effectively reversed by overexpressing P53. This study indicated the potential therapeutic effect of MSC-sEVs on vascular endothelial function maintenance and that the delivery of sEVs carrying miR-125b-5p could prevent endothelial cell ferroptosis by inhibiting P53, thereby protecting the BRB.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956900","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

CD44: a key regulator of iron metabolism, redox balance, and therapeutic resistance in cancer stem cells. CD44：肿瘤干细胞铁代谢、氧化还原平衡和治疗抵抗的关键调节因子

IF 4 2区医学

STEM CELLS Pub Date : 2025-05-27 DOI: 10.1093/stmcls/sxaf024

Taiju Ando, Juntaro Yamasaki, Hideyuki Saya, Osamu Nagano

{"title":"CD44: a key regulator of iron metabolism, redox balance, and therapeutic resistance in cancer stem cells.","authors":"Taiju Ando, Juntaro Yamasaki, Hideyuki Saya, Osamu Nagano","doi":"10.1093/stmcls/sxaf024","DOIUrl":"10.1093/stmcls/sxaf024","url":null,"abstract":"CD44, a multifunctional cell surface protein, has emerged as a pivotal regulator in cancer stem cell (CSC) biology, orchestrating processes such as stemness, metabolic reprogramming, and therapeutic resistance. Recent studies have identified a critical role of CD44 in ferroptosis resistance by stabilizing SLC7A11 (xCT), a key component of the antioxidant defense system, enabling CSCs to evade oxidative stress and sustain tumorigenic potential. Additionally, CD44 regulates intracellular iron metabolism and redox balance, further supporting CSC survival and adaptation to stressful microenvironments. Therapeutic strategies targeting CD44, including ferroptosis inducers and combination therapies, have shown significant potential in preclinical and early clinical settings. Innovations such as CD44-mediated nanocarriers and metabolic inhibitors present novel opportunities to disrupt CSC-associated resistance mechanisms. Furthermore, the dynamic plasticity of CD44 isoforms governed by transcriptional, post-transcriptional, and epigenetic regulation underscores the importance of context-specific therapeutic approaches. This review highlights the multifaceted roles of CD44 in CSC biology, focusing on its contribution to ferroptosis resistance, iron metabolism, and redox regulation. Targeting CD44 offers a promising avenue for overcoming therapeutic resistance and improving the outcomes of refractory cancers. Future studies are needed to refine these strategies and enable their clinical translation.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12126136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954716","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

ZIC1 transcription factor overexpression in segmental bone defects is associated with brown adipogenic and osteogenic differentiation. ZIC1转录因子在节段性骨缺损中的过表达与棕色脂肪形成和成骨分化有关。

IF 4 2区医学

STEM CELLS Pub Date : 2025-05-27 DOI: 10.1093/stmcls/sxaf013

Neelima Thottappillil, Zhao Li, Xin Xing, Shreya Arondekar, Manyu Zhu, Masnsen Cherief, Qizhi Qin, Myles Zhou, Mary Archer, Kristen Broderick, Bruno Pèault, Min Lee, Aaron W James

{"title":"ZIC1 transcription factor overexpression in segmental bone defects is associated with brown adipogenic and osteogenic differentiation.","authors":"Neelima Thottappillil, Zhao Li, Xin Xing, Shreya Arondekar, Manyu Zhu, Masnsen Cherief, Qizhi Qin, Myles Zhou, Mary Archer, Kristen Broderick, Bruno Pèault, Min Lee, Aaron W James","doi":"10.1093/stmcls/sxaf013","DOIUrl":"10.1093/stmcls/sxaf013","url":null,"abstract":"Transcriptional factor regulation is central to the lineage commitment of stem/ progenitor cells. ZIC1 (ZIC family member 1) is a C2H2-type zinc finger transcription factor expressed during development, brown fat, and certain cancers. Previously, we observed that overexpression of ZIC1 induces osteogenic differentiation at the expense of white adipogenic differentiation. In the present study, the feasibility of ZIC1 overexpressed human progenitor cells in critical-sized bone defects was studied. To achieve this, human adipose stem/stromal cells with other without lentiviral ZIC1 overexpression were implanted in a femoral segmental defect model in NOD-SCIDγ mice. Results showed that ZIC1 overexpressed cells induced osteogenic differentiation by protein markers in a critical-sized femoral segment defect compared to empty lentiviral control, although bone union was not observed. The immunohistochemical evaluation showed that implantation of ZIC1 overexpression cells led to an increase in osteoblast antigen expression (RUNX2, OCN), activation of Hedgehog signaling (Patched1), and an increase in brown adipogenesis markers (ZIC1, EBF2). In contrast, no change in bone defect-associated vasculature was observed (CD31, Endomucin). Together, these data suggest that overexpression of the ZIC1 transcription factor in progenitor cells is associated with differentiation towards osteoblastic and brown adipogenic cell fates.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727129","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

Cellular therapies for the prevention and treatment of acute graft-versus-host disease. 细胞疗法预防和治疗急性移植物抗宿主病。

IF 4 2区医学

STEM CELLS Pub Date : 2025-05-27 DOI: 10.1093/stmcls/sxaf009

Daniel Peltier, Van Anh Do-Thi, Timothy Devos, Bruce R Blazar, Tomomi Toubai

{"title":"Cellular therapies for the prevention and treatment of acute graft-versus-host disease.","authors":"Daniel Peltier, Van Anh Do-Thi, Timothy Devos, Bruce R Blazar, Tomomi Toubai","doi":"10.1093/stmcls/sxaf009","DOIUrl":"10.1093/stmcls/sxaf009","url":null,"abstract":"Acute graft-versus-host disease (aGVHD) is a major complication of allogeneic hematopoietic cell transplantation (allo-HCT) that is caused by donor immune cells attacking and damaging host tissues. Immune suppressive small molecule and protein-based therapeutics targeting donor anti-host immune cells are currently used for GVHD prophylaxis and treatment. Even with these therapies, aGVHD progresses to life-threatening steroid-refractory aGVHD (SR-aGVHD) in up to 50% of cases and is a risk factor for the subsequent development of debilitating chronic GVHD. To improve aGVHD-related outcomes, donor graft engineering techniques and adoptive transfer of immune modulatory cells have been explored. Highly rigorous donor graft T-cell depletion approaches have revealed that mitigation of aGVHD can be accompanied by slow immune recovery post-allo-HCT and reduction in anti-microbial and anti-leukemia responses resulting in increased relapse and infection rates, respectively. Recent T-cell separation techniques allowing for precision graft engineering by selectively eliminating aGVHD-causing T-cells (eg, naïve T-cells) without loss of T-cells with beneficial functions and retaining and/or enriching immune regulatory populations (eg, regulatory T-cells (Tregs) or myeloid-derived suppressor cells) have been tested and will continue to improve. Clinical cell-based regulatory therapies have been employed for targeting SR-aGVHD, particularly mesenchymal stem cells (MSCs) and more recently, Tregs. In this review, we summarize aGVHD pathophysiology, highlight newly discovered aGVHD mechanisms, and discuss current and emerging cellular and graft manipulation approaches for aGVHD prevention and treatment.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12111709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672869","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

Inflammatory pathways and the bone marrow microenvironment in inherited bone marrow failure syndromes. 炎症途径和骨髓微环境在遗传性骨髓衰竭综合征。

IF 4 2区医学

STEM CELLS Pub Date : 2025-05-27 DOI: 10.1093/stmcls/sxaf021

Nicholas Neoman, Hye Na Kim, Jacob Viduya, Anju Goyal, Y Lucy Liu, Kathleen M Sakamoto

{"title":"Inflammatory pathways and the bone marrow microenvironment in inherited bone marrow failure syndromes.","authors":"Nicholas Neoman, Hye Na Kim, Jacob Viduya, Anju Goyal, Y Lucy Liu, Kathleen M Sakamoto","doi":"10.1093/stmcls/sxaf021","DOIUrl":"10.1093/stmcls/sxaf021","url":null,"abstract":"Inherited bone marrow failure syndromes (IBMFS) are a diverse group of genetic disorders characterized by insufficient hematopoietic cell production due to blood stem cell dysfunction. The most common syndromes are Fanconi Anemia, Diamond-Blackfan Anemia, and Shwachman-Diamond Syndrome. These conditions share a theme of chronically producing pro-inflammatory cytokines such as TNF-α, IL-1β, IL-6, TGF-β, IFN-I, and IFN-γ. Each of these cytokines can impact the bone marrow microenvironment and drive the pathophysiology of IBMFS. This review aims to provide the latest progress in the field regarding the mechanistic underpinnings of inflammation in these IBMFS, as well as the effect of inflammation on the bone marrow microenvironment. A comprehensive understanding of the inflammation in IBMFS will open new avenues for intervention to restore bone marrow stability and improve patient prognosis. Future research must include targeting these mechanisms to develop novel therapies that can potentially mitigate the effects of chronic inflammation in IBMFS.","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12121359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952420","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

STEM CELLS最新文献