Stem Cell Reviews and Reports最新文献

{"title":"Stem Cell-Derived Exosomes: A Cell-Free Frontier in Peripheral Nerve Regeneration.","authors":"Lin Lin, Lin Yan, Yaqiong Zhu, Yukun Luo","doi":"10.1007/s12015-026-11192-8","DOIUrl":"10.1007/s12015-026-11192-8","url":null,"abstract":"","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"3384-3387"},"PeriodicalIF":4.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148472859","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":"Mitochondrial Communication Networks in the Bone Microenvironment: From the Maintenance of Homeostasis to Translational Interventions for Bone Diseases.","authors":"Wentao Wang, Kun Wang, Wenjing Wang, Xuan Mu, Zhiquan Cheng, Guangzhi Zhang, Xuewen Kang, Yonggang Wang","doi":"10.1007/s12015-026-11190-w","DOIUrl":"10.1007/s12015-026-11190-w","url":null,"abstract":"<p><p>Intercellular mitochondrial transfer has recently emerged as an important concept in bone biology, providing a new framework for understanding immune-metabolic cross-talk within the bone microenvironment. This microenvironment is a dynamic system that is both metabolically active and immunologically complex, and its homeostasis relies on finely tuned communication among multiple cellular populations. Increasing evidence suggests that mitochondrial transfer is a key mechanism integrating these diverse signaling networks. In this review, we systematically summarize recent advances in mitochondrial transfer among osteolineage cells, immune cells, and vascular-associated cells, and we further discuss its multiple roles in bone remodeling, tissue repair, and the pathogenesis of osseous diseases. At the mechanistic level, special emphasis is placed on the Mitochondrial Rho GTPase 1 (MIRO1)-mediated mitochondrial transport pathway, through which mitochondria are transferred from osteolineage cells to myeloid cells, thereby driving metabolic reprogramming and modulating susceptibility to ferroptosis, ultimately helping to suppress excessive osteoclastogenesis. From a pathological perspective, dysregulated mitochondrial transfer is increasingly recognized as a common feature across a range of skeletal disorders. In glucocorticoid-induced osteoporosis (GIOP), impairment of MIRO1-dependent mitochondrial transport promotes ferroptosis resistance in osteoclast precursors. In osteoarthritis, aberrant mitochondria accelerate cartilage degeneration by disrupting coenzyme A (CoA) metabolism through Nudix Hydrolase 8 (NUDT8) and subsequently activating the cGAS-STING signaling pathway. In bone metastasis, inflammatory signals triggered by mitochondrial deoxyribonucleic acid (mtDNA) release exhibit both pro-tumorigenic and anti-tumorigenic regulatory effects. Based on these mechanisms, this manuscript also critically evaluates the translational potential of several therapeutic strategies, including mesenchymal stem cell-derived mitochondrial transplantation, nanocarrier delivery systems, and the modulation of tunneling nanotubes. Overall, targeting intercellular mitochondrial transport may offer new therapeutic opportunities for metabolic intervention and immunomodulation in bone diseases.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"3131-3151"},"PeriodicalIF":4.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148498013","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":"Natural Killer Cell Immunotherapy After Allogeneic Hematopoietic Stem Cell Transplantation in Acute Leukemia Patients: Phase I Clinical Trial.","authors":"Shiva Eskandarian, Amirhossein Izadpanah, Saye Parkhideh, Mahshid Mehdizade, Sahar Parkhideh, Mozhdeh Mohammadian, Mehrshad Seresht-Ahmadi, Mehdi Bakhtiyaridovvombaygi, Abdollah Sabri, Ahmad Gharehbaghian, Abbas Hajifathali, Elham Roshandel","doi":"10.1007/s12015-026-11193-7","DOIUrl":"10.1007/s12015-026-11193-7","url":null,"abstract":"<p><strong>Background: </strong>Immunotherapy offers a promising approach to prevent relapse and transplant complications. Natural killer (NK) cells play a crucial role in the immune system's initial defense against infections and malignant cells. Activation of NK cells with interleukin-15 enhances anti-leukemic immune responses. We conducted this clinical trial to evaluate the safety and efficacy of CD56 + cell infusion in increasing survival and reducing relapse in patients with acute myeloid leukemia.</p><p><strong>Methods: </strong>Three escalating doses of 1 × 10⁶, 3 × 10⁶, and 5 × 10⁶ interleukin-15-activated CD56 + cells/kg derived from peripheral blood of haploidentical donors were injected on days + 7, +14, and + 21 following transplantation. Patients were monitored for adverse events. To evaluate efficacy, bone marrow samples were taken on days + 30 and + 90. On day + 40, the population of NK cells and its correlation with patients' clinical status were evaluated. Besides, immune reconstitution was examined on day + 40. Patients were followed up for one year.</p><p><strong>Results: </strong>The CD56 + cells infusion was safe and not associated with any complications. While survival rates were not statistically different between the intervention and control groups, a trend toward improved survival was observed in the intervention group. Patients with complete remission showed a higher percentage of NK cells on day + 40 than patients who experienced graft rejection, relapse, or death.</p><p><strong>Conclusions: </strong>In this study, we introduce a feasible method for activating CD56 + cells. Although the survival rates of patients in the intervention and control groups did not differ statistically, this study showed that a higher percentage of NK cells on day + 40 is associated with better survival and fewer complications following transplantation.</p><p><strong>Trial registration: </strong>This study was registered at the Iranian Registry of Clinical Trials under code IRCT20230801058996N2 on 2023-09-10.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"3347-3359"},"PeriodicalIF":4.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148664483","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":"Dnmt3L Acetylation as a Post-Translational Switch Linking Extracellular Environment to Epigenetic Stability in Pluripotent Stem Cells.","authors":"Janitri Venkatachala Babu, Kandasamy Nagarajan ArulJothi, Ramya Lakshmi Rajendran, Prakash Gangadaran, Byeong-Cheol Ahn","doi":"10.1007/s12015-026-11183-9","DOIUrl":"10.1007/s12015-026-11183-9","url":null,"abstract":"","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"3381-3383"},"PeriodicalIF":4.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148303213","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":"Cell-Type-Specific Calibration of Mitochondrial Ubiquitination in Stem Cell Fate Decisions.","authors":"Hao-Cheng Liu, Si-Yuan Chen, Nan-Nan Yu, Mei-Hua Jin, Hu-Nan Sun, Ying-Hao Han","doi":"10.1007/s12015-026-11189-3","DOIUrl":"10.1007/s12015-026-11189-3","url":null,"abstract":"<p><p>Stem cell fate decisions-whether to self-renew, differentiate, or senesce-are inextricably linked to the metabolic identity and quality-control status of mitochondria. The ubiquitin-proteasome system and selective autophagy pathways assemble into an integrated surveillance network at the mitochondrial outer membrane that gauges organelle health, sculpts morphology, and transduces metabolic information into lineage-determining transcriptional programmes. This Review examines how the ubiquitination machinery-spanning the canonical PINK1-Parkin axis and non-Parkin E3 ligases including MARCH5, MUL1, and the emerging Cullin-RING component RBX2-orchestrates outer-membrane protein degradation, mitochondria-derived vesicle biogenesis, and the balance between fusion and fission. We discuss how these post-translational events govern stem cell identity across haematopoietic, muscle, neural, mesenchymal, and pluripotent compartments. Recent 2024-2025 advances include an Nicotinamide Adenine Dinucleotide (NAD⁺)-dependent metabolic checkpoint governing haematopoietic stem cell activation and aging, the crystallographic resolution of USP30 inhibitor binding, molecular glue activators that allosterically enhance Parkin RING-domain activity, ClpP-based mitochondria-targeted PROTAC platforms, and HIF-1α/BNIP3-mediated pharmacological rejuvenation of aged mesenchymal stem cells. We further discuss the WAC-PINK1-Parkin axis in mesenchymal stem cell aging, the bidirectional interplay between reactive oxygen species and E3 ligase activity, and the ACC1-FIS1 ubiquitination axis. Finally, we consider the cell-type-specific calibration of mitochondrial ubiquitination as a unifying principle for precision therapeutics and the inverted quality-control logic exploited by cancer stem cells. We propose that the cell-type-specific calibration of mitochondrial ubiquitination-whereby identical molecular events carry divergent functional consequences across stem cell compartments-offers a unifying framework for precision therapeutics.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"3081-3103"},"PeriodicalIF":4.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148424351","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":"Harnessing Endogenous Plasticity Rather than Reprogramming of Mature Cells Will Advance Regenerative Medicine, Cancer Treatment and Rejuvenation.","authors":"Deepa Bhartiya, Nripen Sharma, Anish Tripathi, Ashish Tripathi","doi":"10.1007/s12015-026-11197-3","DOIUrl":"10.1007/s12015-026-11197-3","url":null,"abstract":"<p><p>The successful culture of human embryonic stem (hES) cells from inner cell mass cells of blastocyst stage 'spare' embryos in 1998, followed by induced pluripotent stem (iPS) cells in 2006, which allowed somatic cells to be reprogrammed to pluripotency using the Yamanaka factors, transformed regenerative biology and inspired extensive global efforts towards developing pluripotent stem cell-based applications. However, hES and iPS cells, as well as organoids generated from them, largely retain fetal-like characteristics, which limits their relevance for clinical translation. Concurrently, the prevailing assumption published in leading journals that adult tissues lack endogenous stem cells has led to the belief that mature cells dedifferentiate and reprogram during in vivo regeneration upon chronic injury, and that the appearance of embryonic/fetal markers in diabetes, heart failure, cancer, and many other chronic disease states reflects dedifferentiation of mature cells. We suggest that the prevailing concepts of dedifferentiation and reprogramming, both in vitro and in vivo, require careful re-evaluation. Adult somatic cells possibly do not truly dedifferentiate, neither in vitro nor in vivo. Instead, tissue-resident, pluripotent, very small embryonic-like stem cells (VSELs) in multiple organs account for the observed biology. In vitro \"reprogramming\" responses to Yamanaka factors likely reflect selective activation and expansion of VSELs/early progenitors rather than the dedifferentiation/ reprogramming of mature adult somatic cells. Likewise, the embryonic/fetal-like signatures reported in multiple disease states including cancer reflect expansion of immature tissue-specific progenitors that arise from VSELs but fail to differentiate normally due to a damaged microenvironment in vivo. Therapeutic strategies involving transplantation of MSCs, MUSE cells, or their secreted exosomes improve disease outcomes, possibly by restoring the damaged niche that supports functional tissue repair by VSELs. Although direct evidence to support this is lacking at present, recognising the central role of VSELs/progenitors and their niche in maintaining tissue homeostasis in vivo could resolve existing roadblocks and guide more effective endogenous regenerative therapies for diseased tissues and age-related dysfunctions.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"3417-3438"},"PeriodicalIF":4.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148621146","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":"Unraveling the Multifaceted Roles of Tissue-Resident Macrophages: Focus on Bone Homeostasis and Regeneration.","authors":"Xinyi Feng, Qifeng Wu, Yangxuanyu Yan, Baofu Yu, Zhu Zhu, Yunbo Qiao, Jiao Wei","doi":"10.1007/s12015-026-11202-9","DOIUrl":"10.1007/s12015-026-11202-9","url":null,"abstract":"<p><p>Tissue-resident macrophages (TRMs) are essential regulators of tissue homeostasis and regeneration across multiple organs. While their roles in systems such as the liver, brain, and skin have been increasingly clarified, their functions in bone remain markedly understudied. This review begins by outlining the established roles of TRMs in immune regulation and tissue repair to provide a conceptual framework for understanding their skeletal counterparts, known as osteal resident macrophages (ORMs). We then summarize current evidence for ORM involvement in bone homeostasis and regeneration and highlight the major challenges in bone TRM research. Clarifying the cellular identity and regulation of ORMs will help define their roles in bone homeostasis and repair, and inform future strategies for modulating macrophage function in skeletal disease. Tissue-resident macrophages (TRMs) are essential regulators of tissue homeostasis and regeneration across multiple organs. While their roles in systems such as the liver, brain, and skin have been increasingly clarified, their functions in bone remain markedly understudied. This review begins by outlining the established roles of TRMs in immune regulation and tissue repair to provide a conceptual framework for understanding their skeletal counterparts, known as osteal resident macrophages (ORMs). We then summarize current evidence for ORM involvement in bone homeostasis and regeneration and highlight the major challenges in bone TRM research. Clarifying the cellular identity and regulation of ORMs will help define their roles in bone homeostasis and repair, and inform future strategies for modulating macrophage function in skeletal disease.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"3227-3247"},"PeriodicalIF":4.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148664515","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":"Rejuvenating the Niche Before the Cell: Microenvironmental Reprogramming as the Central Strategy for Pulp Regeneration in the Aged Teeth.","authors":"Mohammed Zayed, Byung-Hoon Jeong","doi":"10.1007/s12015-026-11207-4","DOIUrl":"10.1007/s12015-026-11207-4","url":null,"abstract":"","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"3396-3399"},"PeriodicalIF":4.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679751","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":"Revitalizing Mesenchymal Stem Cells: Overcoming the Barriers of Diabetic Glucotoxicity in Regenerative Medicine.","authors":"Chengyuan Bao, Cunmin Zhou, Tongxu Zeng, Xiaoqin Ha","doi":"10.1007/s12015-026-11191-9","DOIUrl":"10.1007/s12015-026-11191-9","url":null,"abstract":"","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"3388-3391"},"PeriodicalIF":4.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148472856","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":"A Letter Matters: ADRB2 rs1042713 c.46A Modulates Anti-osteogenic Effect of Epinephrine in Human Mesenchymal Stem Cells.","authors":"Olga Krasnova, Julia Sopova, Valeriia Borodii, Polina Semenova, Olga Bystrova, Irina Neganova","doi":"10.1007/s12015-026-11185-7","DOIUrl":"10.1007/s12015-026-11185-7","url":null,"abstract":"<p><p>Osteoporosis (OP) is a systemic bone disease affecting millions worldwide, characterized by long-term asymptomatic development that manifests in low-energy fractures. Due to their high stability, genetic markers represent a promising strategy for early diagnostics. The ADRB2 rs1042713 polymorphism is one such marker, considered as a potential predictor for OP. Although the anti-osteogenic role of the β2-adrenergic receptor is well-established, debate continues on which allele (G or A) of this polymorphism drives bone deterioration. In this study, we examined the influence of the ADRB2 rs1042713 G/G and A/A variants on osteogenic differentiation in patient-derived mesenchymal stem cells (MSCs) under treatment with the endogenous agonist epinephrine. We show that epinephrine (whose levels are often elevated in comorbid conditions) drastically impairs osteogenic differentiation, specifically at the matrix mineralization stage in MSCs A/A. Epinephrine fails to activate the canonical β2-adrenergic receptor pathway and promotes receptor perinuclear and nuclear localization in MSCs A/A. Crucially, metformin, a common anti-diabetic drug, rescues this anti-osteogenic effect. These results open new perspectives for early diagnostics by identifying epinephrine sensitivity as a critical factor, while also suggesting a potential therapeutic strategy to counteract epinephrine detrimental effect in individuals carrying the ADRB2 rs1042713 A-allele.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":"3281-3303"},"PeriodicalIF":4.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148362470","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}