Stem Cells Translational Medicine最新文献_第5页

Guiding pluripotent stem cell therapies past the immune system. 引导多能干细胞疗法越过免疫系统。

IF 5.9 2区医学

Stem Cells Translational Medicine Pub Date : 2026-07-20 DOI: 10.1093/stcltm/szag051

Hannah A Pizzato, Deepta Bhattacharya

引用次数: 0

The role of endothelial colony forming cells in the treatment of limb ischaemia: challenges in clinical translation. 内皮集落形成细胞在肢体缺血治疗中的作用：临床翻译中的挑战。

IF 5.9 2区医学

Stem Cells Translational Medicine Pub Date : 2026-06-27 DOI: 10.1093/stcltm/szag033

Christine Ayu Lagonda, Caomhán J Lyons, Yaqiong Liu, Michael Creane, Timothy O'Brien

{"title":"The role of endothelial colony forming cells in the treatment of limb ischaemia: challenges in clinical translation.","authors":"Christine Ayu Lagonda, Caomhán J Lyons, Yaqiong Liu, Michael Creane, Timothy O'Brien","doi":"10.1093/stcltm/szag033","DOIUrl":"10.1093/stcltm/szag033","url":null,"abstract":"Endothelial colony forming cells (ECFCs) are emerging as a promising therapeutic option for treating various vascular and degenerative disorders. These cells, also known as endothelial progenitor cells, which play a crucial role in angiogenesis, may be a promising therapeutic in the management of chronic limb-threatening ischaemia (CLTI). CLTI requires the regeneration of surrounding niche cells through vascular repair, which is often compromised by oxygen and nutrient deprivation. ECFCs have been extensively studied for their unique endothelial properties and their capacity for vascular repair. Numerous preclinical studies have been initiated to explore the safety and efficacy of ECFCs in treating CLTI. However, translating ECFC based therapies into clinical practice faces significant challenges, and there has been very limited translation to therapeutic studies in humans. Chief among these challenges is the inherent heterogeneity within ECFC populations, shaped by factors such as donor characteristics, tissue origin, and underlying health conditions. Despite this challenge, in vivo studies in animal models have laid the groundwork for potential clinical translation of ECFCs. These studies underscore the successful application of ECFCs in vascular repair and regeneration, emphasizing the specific parameters used in in vivo studies that contribute to a broader understanding of ECFCs and paving the way for their future clinical use. This report will review the current status of preclinical studies of the use of ECFCs in limb ischaemia and the challenges associated with human translation.","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 7","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13323062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148369739","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

Inhibition of inflammation and senescence with azole compound C7 enables expansion of hematopoietic stem and progenitor cells. 唑类化合物C7抑制炎症和衰老，使造血干细胞和祖细胞扩增。

IF 5.9 2区医学

Stem Cells Translational Medicine Pub Date : 2026-06-27 DOI: 10.1093/stcltm/szag037

Ze Hui Kok, Lin Ming Lee, Kelvin Y H Liu, John Ouyang, Vikneswari Rajasegaran, Samantha P S Lim, Jui Wan Loh, Jing Yi Lee, Abner H Lim, Cedric Chuan Young Ng, Jason Yongsheng Chan, Sudipto Bari, William Ying Khee Hwang

{"title":"Inhibition of inflammation and senescence with azole compound C7 enables expansion of hematopoietic stem and progenitor cells.","authors":"Ze Hui Kok, Lin Ming Lee, Kelvin Y H Liu, John Ouyang, Vikneswari Rajasegaran, Samantha P S Lim, Jui Wan Loh, Jing Yi Lee, Abner H Lim, Cedric Chuan Young Ng, Jason Yongsheng Chan, Sudipto Bari, William Ying Khee Hwang","doi":"10.1093/stcltm/szag037","DOIUrl":"10.1093/stcltm/szag037","url":null,"abstract":"Human hematopoietic stem and progenitor cells (HSPCs) derived from umbilical cord blood (UCB) are often insufficient in quantity for transplantation, necessitating efforts for ex vivo expansion. We previously developed a novel azole-based small molecule, C7, as a structural analog of the p38 mitogen-activated protein kinase inhibitor SB203580. C7 mediated robust ex vivo expansion of UCB HSPCs from unselected mononuclear cells, compared to its structural analogs and other published compounds. However, the molecular underpinnings of C7's potency remained unclear. In this work, we demonstrate that C7 preferentially enhances the proliferation and viability of early HSPC subsets upon direct culture with pre-isolated HSPCs, while limiting mitochondrially-derived reactive oxygen species production linked to oxidative stress. C7 treatment enhances hematopoietic stem cell self-renewal and in vivo multilineage reconstitution without T- or myeloid lineage bias. Unlike existing p38 inhibitors, C7 targets multiple kinases and pathways to achieve superior HSPC expansion through suppression of NFκB and IL-10 inflammatory signaling and attenuation of stress/senescence‑associated markers (eg, SERPINB2 and CDKN1A/p21). This mechanism of action of C7 is distinct from those of other existing compounds used for ex vivo HSPC expansion and has implications for application in other ex vivo culture platforms and clinical settings.","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 7","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13323081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148369669","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

Five-year follow-up outcomes after phase 1 trial of mesenchymal stromal cells for periventricular hemorrhagic infarction in preterm infants. 间充质间质细胞治疗早产儿脑室周围出血性梗死后的5年随访结果。

IF 5.9 2区医学

Stem Cells Translational Medicine Pub Date : 2026-05-18 DOI: 10.1093/stcltm/szag030

Misun Yang, So Yoon Ahn, Se In Sung, Yun Sil Chang, Won Soon Park

{"title":"Five-year follow-up outcomes after phase 1 trial of mesenchymal stromal cells for periventricular hemorrhagic infarction in preterm infants.","authors":"Misun Yang, So Yoon Ahn, Se In Sung, Yun Sil Chang, Won Soon Park","doi":"10.1093/stcltm/szag030","DOIUrl":"10.1093/stcltm/szag030","url":null,"abstract":"Periventricular hemorrhagic infarction (PVHI), commonly referred to as grade 4 intraventricular hemorrhage, is a serious neurological disorder in premature infants with no established disease-modifying therapy. This study evaluated the long-term safety and outcomes of intraventricular administration of mesenchymal stromal cells (MSCs) in premature infants with PVHI who previously participated in a phase I trial, with follow-up through a corrected age (CA) of 5 years. Nine infants were included, of whom four had a PVHI score of 2 and five had a score of 3. No significant short-term or long-term adverse events, including tumorigenicity, were observed. Infants with higher PVHI severity (score 3) showed more frequent long-term adverse outcomes, including a mental development index <70 on the Bayley Scales of Infant and Toddler Development II at a CA of 2 years, developmental impairment as assessed by the Korean Developmental Screening Test, and cerebral palsy (CP) with Gross Motor Function Classification System (GMFCS) ≥3 at both CA 2 and 5 years. Lower intact brain volume ratio strongly correlates with the presence of CP with GMFCS ≥3. Intraventricular MSC administration appeared safe and feasible over 5 years; however, baseline PVHI severity remained the strongest predictor of long-term neurodevelopmental outcomes. These findings support the need for larger, controlled trials to further evaluate the therapeutic potential of MSCs for PVHI. ClinicalTrials.gov Identifier: NCT02673788.","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 6","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13235719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148164319","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

Addressing bioenergetic deficits and restoring mitochondrial health in transplanted islets using mesenchymal stem cells. 利用间充质干细胞解决移植胰岛的生物能量缺陷和恢复线粒体健康。

IF 5.9 2区医学

Stem Cells Translational Medicine Pub Date : 2026-05-18 DOI: 10.1093/stcltm/szag038

Rosita Primavera, Abantika Ganguly, Reza Yarani, Lili Bettencourt, Shobha Regmi, Shashank Chetty, Jing Wang, Michele Guindani, Ramasamy Paulmurugan, Avnesh S Thakor

{"title":"Addressing bioenergetic deficits and restoring mitochondrial health in transplanted islets using mesenchymal stem cells.","authors":"Rosita Primavera, Abantika Ganguly, Reza Yarani, Lili Bettencourt, Shobha Regmi, Shashank Chetty, Jing Wang, Michele Guindani, Ramasamy Paulmurugan, Avnesh S Thakor","doi":"10.1093/stcltm/szag038","DOIUrl":"10.1093/stcltm/szag038","url":null,"abstract":"During the process of islet transplantation, islets undergo isolation and are then introduced into a new microenvironment where they need to adapt and revascularize. This transition imposes substantial stress on islets, leading to mitochondrial dysfunction and oxidative stress, adversely affecting islet function and vitality. Mesenchymal stem cells (MSCs) offer a promising therapy to mitigate these adverse effects by restoring their bioenergetic capacity and overall functionality of islets. Our study investigates how human MSCs (hMSCs) from different sources-adipose tissue (AD), bone marrow (BM), and umbilical cord (UC)-can restore the bioenergetic capacity of inflamed pancreatic islets. We assess how hMSCs can improve islet survival, function, and mitochondrial health, by analyzing key mitochondrial oxidative stress-related genes. In addition, this study examines the functional effect of co-transplanting islets with hMSCs in vivo in diabetic mice. hMSCs, particularly those from UC and BM, can effectively sustain islet viability, enhance mitochondrial function, and alleviate oxidative stress, as evidenced by increased expression of key mitochondrial markers such as PPARGC1A, TOMM20, and Sod2. Furthermore, co-transplantation of hMSCs with sub-therapeutic islet numbers leads to long-term improvements in glucose regulation, with UC-hMSCs showing better short-term efficacy (100% of diabetic mice receiving islets with UC-hMSCs recovered their blood glucose levels back to normal at 4 weeks post-transplantation, vs. 80% of those transplanted with BM-hMSCs, 60% with AD-hMSCs, and 16% for islets alone). These findings highlight the potential of hMSC-therapies for islet transplantation, underscoring the need to select the optimal MSC source to maximize the therapeutic outcome of transplanted islets.","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 7","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13311671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346320","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

Extracellular vesicles from SB431542-conditioned human adipose-derived stem cells enhance in vitro and in vivo osteogenesis via a miR-20a-5p-BAMBI-BMP/canonical Wnt signaling axis. 来自sb431542条件的人脂肪来源干细胞的细胞外囊泡通过miR-20a-5p-BAMBI-BMP/典型Wnt信号轴增强体外和体内成骨。

IF 5.9 2区医学

Stem Cells Translational Medicine Pub Date : 2026-05-18 DOI: 10.1093/stcltm/szag026

Julika Huber, Michael T Longaker, Natalina Quarto

{"title":"Extracellular vesicles from SB431542-conditioned human adipose-derived stem cells enhance in vitro and in vivo osteogenesis via a miR-20a-5p-BAMBI-BMP/canonical Wnt signaling axis.","authors":"Julika Huber, Michael T Longaker, Natalina Quarto","doi":"10.1093/stcltm/szag026","DOIUrl":"10.1093/stcltm/szag026","url":null,"abstract":"Background: Critical-sized bone defects resulting from tumors, trauma, or surgery present a significant clinical challenge due to its poor self-regenerating capabilities and limited therapeutic options. Mesenchymal stem cells (MSCs) have shown promise in bone regeneration, possibly mediated through their secretion of bioactive factors rather than direct engraftment and differentiation. MSC-derived extracellular vesicles (EVs) deliver micro-RNAs (miRs), proteins, and lipids that may modulate bone regeneration.Methods: EVs were isolated by differential ultracentrifugation from osteogenically induced human adipose-derived stem cells (hASCs), treated with or without the small molecule SB431542, an inhibitor of TGFβ signaling (EV-hASCs[-/+]SB). EVs were characterized using western blot and nanoparticle tracking analysis. hASCs were cultured with EV-hASCs[-/+]SBs to assess bone regeneration in vitro. Bone regeneration was assessed in vivo in calvarial defects treated with (EV-hASCs[-/+]SB). EV \"cargo\" was analyzed for miR-content.Results: Enhanced osteogenesis is shown in vitro and in vivo upon treatment with EV-hASCs[+]SB. EV-hASCs[+]SB-enriched-miR-20a-5p was identified as a modulating factor in osteogenesis, silencing BAMBI and enhancing early downstream phosphorylation of SMAD1/5 and late activation of β-catenin in hASCs undergoing osteogenic differentiation, targets of bone morphogenetic protein (BMP) and canonical Wnt (cWnt) signaling pathways.Conclusion: EVs act as carriers for miR-mediated pro-osteogenic signaling, harnessing the therapeutic potential of MSCs in the context of bone tissue repair.","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 6","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13199063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148017367","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

HO-1-modified umbilical cord MSCs alleviate pulmonary arterial hypertension by reducing inflammation and endothelial dysfunction. ho -1修饰的脐带间充质干细胞通过减少炎症和内皮功能障碍减轻肺动脉高压。

IF 5.9 2区医学

Stem Cells Translational Medicine Pub Date : 2026-05-18 DOI: 10.1093/stcltm/szag036

Riken Chen, Xing Chen, Limei Liang, Huan Li, Liping Xu, Dongjie Huang, Yong Liu, Deyi Zhou, Weilong Ye, Shuyue Zhou, Yihuan Su, Dekang Nie, Zhenzhen Zheng, Yan Deng

{"title":"HO-1-modified umbilical cord MSCs alleviate pulmonary arterial hypertension by reducing inflammation and endothelial dysfunction.","authors":"Riken Chen, Xing Chen, Limei Liang, Huan Li, Liping Xu, Dongjie Huang, Yong Liu, Deyi Zhou, Weilong Ye, Shuyue Zhou, Yihuan Su, Dekang Nie, Zhenzhen Zheng, Yan Deng","doi":"10.1093/stcltm/szag036","DOIUrl":"10.1093/stcltm/szag036","url":null,"abstract":"Objective: To evaluate the efficacy of MSCs-HO-1 in pulmonary arterial hypertension (PAH) and explore the underlying mechanisms.Methods: HO-1 expression and localization in lung tissues and vessels were assessed using spatial transcriptomics and single-cell RNA sequencing analyses of human PAH. MSCs-HO-1 were intravenously administered in rat and mouse PAH models (MCT-induced and SuHx). Hemodynamics (RVSP), right ventricular hypertrophy index (RVHI), survival rate, and vascular remodeling were assessed by HE staining and α-SMA immunostaining. Inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-18, IL-10, TGF-β, IL-4, IL-1Ra), ROS levels, and endothelial molecules [nitric oxide (NO) and prostaglandin I2 (PGI2)] were measured. RNA sequencing (RNA-seq) of PAECs was followed by pathway analysis and MAPK validation.Results: HO-1 was downregulated in PAH patients and models, mainly in the vascular endothelium. MSCs-HO-1 significantly reduced RVSP, RVHI, vascular remodeling, and improved survival compared to unmodified MSCs and HO-1 alone. MSCs-HO-1 inhibited pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-18), increased anti-inflammatory factors (IL-10, TGF-β, IL-4, IL-1Ra), reduced ROS, and restored NO/PGI2. PAEC migration and proliferation abnormalities were corrected. RNA-seq revealed multiple synergistic pathways, with MAPK playing a key role in endothelial protection.Conclusion: MSCs-HO-1 enhances endothelial function and pulmonary vascular remodeling by modulating antioxidant and immune responses, restoring NO-PGI2 signaling, and suppressing MAPK-mediated inflammation, providing more stable and significant effects than MSCs or HO-1 alone.","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 7","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13311674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346368","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

Genomic stability of human pluripotent stem cells: advances in research and screening criteria. 人类多能干细胞的基因组稳定性：研究进展和筛选标准。

IF 5.9 2区医学

Stem Cells Translational Medicine Pub Date : 2026-05-18 DOI: 10.1093/stcltm/szag040

Congge Li, Manqing Long, Lifeng Xiang, Zongyong Ai, Yu Yin

引用次数: 0

Low-intensity pulsed ultrasound regulates the osteogenic-adipogenic differentiation balance of rat adipose-derived stem cells via the PI3K/AKT-SREBF1 signaling axis. 低强度脉冲超声通过PI3K/AKT-SREBF1信号轴调控大鼠脂肪干细胞成骨-成脂分化平衡。

IF 5.9 2区医学

Stem Cells Translational Medicine Pub Date : 2026-05-18 DOI: 10.1093/stcltm/szag032

Wenzhong Hu, Zhihao Zhao, Qiuling Zhang, Pei Gong, Xinyu Wang, Cong Han, Xinzhe Gao, Jie Long

{"title":"Low-intensity pulsed ultrasound regulates the osteogenic-adipogenic differentiation balance of rat adipose-derived stem cells via the PI3K/AKT-SREBF1 signaling axis.","authors":"Wenzhong Hu, Zhihao Zhao, Qiuling Zhang, Pei Gong, Xinyu Wang, Cong Han, Xinzhe Gao, Jie Long","doi":"10.1093/stcltm/szag032","DOIUrl":"10.1093/stcltm/szag032","url":null,"abstract":"Rat adipose-derived stem cells (rADSCs) are widely used in bone tissue engineering (BTE). Low-intensity pulsed ultrasound (LIPUS) can modulate stem cell fate; however, its precise regulatory effects on ADSC lineage commitment remain unclear. This study aimed to elucidate how LIPUS regulates the osteogenic-adipogenic differentiation balance of rADSCs. We first performed cell proliferation and differentiation induction assays, which demonstrated that LIPUS significantly enhanced osteogenic differentiation while simultaneously suppressing adipogenesis, without affecting rADSC proliferation. Subsequently, transcriptome sequencing and protein-protein interaction analysis identified sterol regulatory element binding transcription factor 1 (Srebf1) as a pivotal regulatory node in LIPUS-modulated osteogenic-adipogenic differentiation. Rescue experiments further confirmed that LIPUS rescued the Srebf1 overexpression phenotype by restoring osteogenic potential and attenuating adipogenesis. Mechanistically, LIPUS downregulated SREBF1 expression and inhibited its nuclear translocation by inhibiting PI3K/AKT signaling, as evidenced by synergistic effects with the PI3K-specific inhibitor LY294002. Finally, a rat cranial defect model was established to validate the osteogenic potential of LIPUS in vivo. LIPUS significantly enhanced bone defect repair, even in the presence of Srebf1-overexpressing rADSCs. Collectively, our findings suggest that SREBF1, a canonical transcription factor in lipid metabolism, also functions as a mechanoresponsive regulator in cell fate determination. Furthermore, LIPUS promotes bone regeneration by shifting the osteogenic-adipogenic differentiation balance in rADSCs toward osteogenesis through suppression of PI3K/AKT-SREBF1 pathway, thereby providing a potential therapeutic strategy for BTE.","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 7","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13311682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346408","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

The mitochondria-targeting compound PTC299 enhances megakaryocyte and platelet production. 靶向线粒体的化合物PTC299可促进巨核细胞和血小板的产生。

IF 5.9 2区医学

Stem Cells Translational Medicine Pub Date : 2026-05-18 DOI: 10.1093/stcltm/szag035

Xiaoli Wang, Meijuan Xia, Yifei Cai, Ziqi Huo, Yao Zhong, Pei Su, Cuicui Liu, Hongtao Wang, Xiangchun Shen, Fei Wang, Jianwei Xu, Jiaxi Zhou

{"title":"The mitochondria-targeting compound PTC299 enhances megakaryocyte and platelet production.","authors":"Xiaoli Wang, Meijuan Xia, Yifei Cai, Ziqi Huo, Yao Zhong, Pei Su, Cuicui Liu, Hongtao Wang, Xiangchun Shen, Fei Wang, Jianwei Xu, Jiaxi Zhou","doi":"10.1093/stcltm/szag035","DOIUrl":"10.1093/stcltm/szag035","url":null,"abstract":"Backgroud: Thrombocytopenia is a common complication of various clinical conditions, resulting from impaired megakaryocyte function, reduced platelet production, or excessive platelet destruction. Current treatments, including platelet transfusions and thrombopoietin receptor agonists, are limited by platelet supply constraints and risks such as thrombotic complications. Emerging research highlights the role of mitochondrial-related biological processes or components in thrombopoiesis, yet targeted therapeutics remain scarce.Methods: In this study, we investigated mitochondria-targeted compounds for their potential to enhance megakaryocyte and platelet productionusing a fetal liver megakaryocyte differentiation and platelet culture system, and explored their effects on in vivo megakaryocyte and platelet production using a radiation damage-induced thrombocytopenia mouse model.Results: Our findings identify PTC299, a dihydroorotate dehydrogenase and VEGFA mRNA translation inhibitor, as a promising pro-plateletogenic agent. PTC299 not only enhances megakaryocyte and platelet production in vitro but also accelerates their recovery in a mouse model of radiation-induced thrombocytopenia. Additionally, PTC299 alleviates irradiation-induced splenomegaly.Conclusion: PTC299 promotes megakaryocyte differentiation and platelet generation both in vitro and in vivo, demonstrating potential values for thrombocytopenia treatment and platelet regeneration.","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":"15 7","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13311664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148346411","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