npj Regenerative Medicine最新文献_第6页

Inflammation-suppressing cornea-in-a-syringe with anti-viral GF19 peptide promotes regeneration in HSV-1 infected rabbit corneas. 含有抗病毒 GF19 肽的抑制炎症角膜注射器可促进 HSV-1 感染兔角膜的再生。

IF 7.2 1区医学

npj Regenerative Medicine Pub Date : 2024-03-01 DOI: 10.1038/s41536-024-00355-1

Egidijus Simoliunas, Inés Ruedas-Torres, Yolanda Jiménez-Gómez, Elle Edin, Mozhgan Aghajanzadeh-Kiyaseh, Mostafa Zamani-Roudbaraki, Rimvydas Asoklis, Milda Alksne, Neethi C Thathapudi, Bijay K Poudel, Ieva Rinkunaite, Kasparas Asoklis, Monika Iesmantaite, Laura Ortega-Llamas, Almantas Makselis, Marcelo Munoz, Daiva Baltriukiene, Virginija Bukelskiene, Jaime Gómez-Laguna, Miguel González-Andrades, May Griffith

{"title":"Inflammation-suppressing cornea-in-a-syringe with anti-viral GF19 peptide promotes regeneration in HSV-1 infected rabbit corneas.","authors":"Egidijus Simoliunas, Inés Ruedas-Torres, Yolanda Jiménez-Gómez, Elle Edin, Mozhgan Aghajanzadeh-Kiyaseh, Mostafa Zamani-Roudbaraki, Rimvydas Asoklis, Milda Alksne, Neethi C Thathapudi, Bijay K Poudel, Ieva Rinkunaite, Kasparas Asoklis, Monika Iesmantaite, Laura Ortega-Llamas, Almantas Makselis, Marcelo Munoz, Daiva Baltriukiene, Virginija Bukelskiene, Jaime Gómez-Laguna, Miguel González-Andrades, May Griffith","doi":"10.1038/s41536-024-00355-1","DOIUrl":"10.1038/s41536-024-00355-1","url":null,"abstract":"Pathophysiologic inflammation, e.g., from HSV-1 viral infection, can cause tissue destruction resulting in ulceration, perforation, and ultimately blindness. We developed an injectable Cornea-in-a-Syringe (CIS) sealant-filler to treat damaged corneas. CIS comprises linear carboxylated polymers of inflammation-suppressing 2-methacryloyloxyethyl phosphorylcholine, regeneration-promoting collagen-like peptide, and adhesive collagen-citrate glue. We also incorporated GF19, a modified anti-viral host defense peptide that blocked HSV-1 activity in vitro when released from silica nanoparticles (SiNP-GF19). CIS alone suppressed inflammation when tested in a surgically perforated and HSV-1-infected rabbit corneal model, allowing tissue and nerve regeneration. However, at six months post-operation, only regenerated neocorneas previously treated with CIS with SiNP-GF19 had structural and functional features approaching those of normal healthy corneas and were HSV-1 virus-free. We showed that composite injectable biomaterials can be designed to allow regeneration by modulating inflammation and blocking viral activity in an infected tissue. Future iterations could be optimized for clinical application.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"9 1","pages":"11"},"PeriodicalIF":7.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10907611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140013748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Biological study of skin wound treated with Alginate/Carboxymethyl cellulose/chorion membrane, diopside nanoparticles, and Botox A. 使用海藻酸盐/羧甲基纤维素/绒毛膜、二肽纳米粒子和肉毒杆菌毒素 A 治疗皮肤伤口的生物学研究。

IF 7.2 1区医学

npj Regenerative Medicine Pub Date : 2024-02-27 DOI: 10.1038/s41536-024-00354-2

Naimeh Mahheidari, Mohammad Kamalabadi-Farahani, Mohammad Reza Nourani, Amir Atashi, Morteza Alizadeh, Niloofar Aldaghi, Majid Salehi

{"title":"Biological study of skin wound treated with Alginate/Carboxymethyl cellulose/chorion membrane, diopside nanoparticles, and Botox A.","authors":"Naimeh Mahheidari, Mohammad Kamalabadi-Farahani, Mohammad Reza Nourani, Amir Atashi, Morteza Alizadeh, Niloofar Aldaghi, Majid Salehi","doi":"10.1038/s41536-024-00354-2","DOIUrl":"10.1038/s41536-024-00354-2","url":null,"abstract":"A hydrogel-based wound dressing with desirable properties is necessary for achieving functional skin integrity post-injury. This study focuses on preparing a hydrogel using Alginate/Carboxymethyl cellulose (Alg/CMC) as a base material. To evaluate its regenerative effects on full-thickness wounds, diopside nanoparticles and Botulinum toxin A (BTX-A) were incorporated into the hydrogel along with chorion membrane. The diopside nanoparticles (DNPs) act as a proangiogenic factor, promoting proliferation and regulating inflammation, while the chorion membrane facilitates these processes. Additionally, BTX-A prevents scar formation and aids in wound closure. The nanoparticles and hydrogel were characterized using various techniques, and their cytocompatibility was assessed. In vivo studies and quantitative polymerase chain reaction analysis showed that wound area reduction was significant after two weeks of treatment with the Alg/CMC/ChNPs/DNPs/BTX-A hydrogel. Overall, this scaffold demonstrated potential for promoting tissue regeneration and new epithelization formation, making it a promising candidate for enhancing skin restoration in wound treatments.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"9 1","pages":"9"},"PeriodicalIF":7.2,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10899239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139984490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Skeletal muscle regeneration after extensive cryoinjury of caudal myomeres in adult zebrafish. 成年斑马鱼尾部肌球大面积冷冻损伤后的骨骼肌再生。

IF 7.2 1区医学

npj Regenerative Medicine Pub Date : 2024-02-20 DOI: 10.1038/s41536-024-00351-5

Hendrik Oudhoff, Vincent Hisler, Florian Baumgartner, Lana Rees, Dogan Grepper, Anna Jaźwińska

{"title":"Skeletal muscle regeneration after extensive cryoinjury of caudal myomeres in adult zebrafish.","authors":"Hendrik Oudhoff, Vincent Hisler, Florian Baumgartner, Lana Rees, Dogan Grepper, Anna Jaźwińska","doi":"10.1038/s41536-024-00351-5","DOIUrl":"10.1038/s41536-024-00351-5","url":null,"abstract":"Skeletal muscles can regenerate after minor injuries, but severe structural damage often leads to fibrosis in mammals. Whether adult zebrafish possess the capacity to reproduce profoundly destroyed musculature remains unknown. Here, a new cryoinjury model revealed that several myomeres efficiently regenerated within one month after wounding the zebrafish caudal peduncle. Wound clearance involved accumulation of the selective autophagy receptor p62, an immune response and Collagen XII deposition. New muscle formation was associated with proliferation of Pax7 expressing muscle stem cells, which gave rise to MyoD1 positive myogenic precursors, followed by myofiber differentiation. Monitoring of slow and fast muscles revealed their coordinated replacement in the superficial and profound compartments of the myomere. However, the final boundary between the muscular components was imperfectly recapitulated, allowing myofibers of different identities to intermingle. The replacement of connective with sarcomeric tissues required TOR signaling, as rapamycin treatment impaired new muscle formation, leading to persistent fibrosis. The model of zebrafish myomere restoration may provide new medical perspectives for treatment of traumatic injuries.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"9 1","pages":"8"},"PeriodicalIF":7.2,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10879182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139914055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Matrix-bound nanovesicle-associated IL-33 supports functional recovery after skeletal muscle injury by initiating a pro-regenerative macrophage phenotypic transition. 与基质结合的纳米囊泡相关的IL-33通过启动有利于再生的巨噬细胞表型转变，支持骨骼肌损伤后的功能恢复。

IF 6.4 1区医学

npj Regenerative Medicine Pub Date : 2024-01-27 DOI: 10.1038/s41536-024-00346-2

J G Bartolacci, M N Behun, J P Warunek, T Li, A Sahu, G K Dwyer, A Lucas, J Rong, F Ambrosio, H R Turnquist, S F Badylak

{"title":"Matrix-bound nanovesicle-associated IL-33 supports functional recovery after skeletal muscle injury by initiating a pro-regenerative macrophage phenotypic transition.","authors":"J G Bartolacci, M N Behun, J P Warunek, T Li, A Sahu, G K Dwyer, A Lucas, J Rong, F Ambrosio, H R Turnquist, S F Badylak","doi":"10.1038/s41536-024-00346-2","DOIUrl":"10.1038/s41536-024-00346-2","url":null,"abstract":"Injuries to skeletal muscle are among the most common injuries in civilian and military populations, accounting for nearly 60% of extremity injuries. The standard of care for severe extremity injury has been focused upon limb salvage procedures and the utilization of tissue grafts or orthotics in conjunction with rehabilitation to avoid amputation. Nonetheless, many patients have persistent strength and functional deficits that permanently impact their quality of life. Preclinical and clinical studies have shown that partial restoration of functional skeletal muscle tissue following injury can be achieved by the implantation of a biologic scaffold composed of extracellular matrix (ECM). These favorable outcomes are mediated, at least in part, through local immunomodulation. The mechanisms underlying this immunomodulatory effect, however, are poorly understood. The present study investigates a potential mechanistic driver of the immunomodulatory effects; specifically, the effect of selected ECM components upon inflammation resolution and repair. Results show that the host response to skeletal muscle injury is profoundly altered and functional recovery decreased in il33-/- mice compared to age- and sex-matched wildtype counterparts by 14 days post-injury. Results also show that IL-33, contained within matrix-bound nanovesicles (MBV), supports skeletal muscle regeneration by regulating local macrophage activation toward a pro-remodeling phenotype via canonical and non-canonical pathways to improve functional recovery from injury compared to untreated il33-/- counterparts. Taken together, these data suggest that MBV and their associated IL-33 cargo represent a novel homeostatic signaling mechanism that contributes to skeletal muscle repair.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"9 1","pages":"7"},"PeriodicalIF":6.4,"publicationDate":"2024-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10821913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139572147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Author Correction: Capacitive interdigitated system of high osteoinductive/conductive performance for personalized acting-sensing implants. 作者更正：用于个性化作用传感植入体的高骨传导/电传导性能的电容互斥系统

IF 7.2 1区医学

npj Regenerative Medicine Pub Date : 2024-01-20 DOI: 10.1038/s41536-024-00350-6

Bárbara M de Sousa, Clara R Correia, Jorge A F Ferreira, João F Mano, Edward P Furlani, Marco P Soares Dos Santos, Sandra I Vieira

引用次数: 0

MSCs mediate long-term efficacy in a Crohn’s disease model by sustained anti-inflammatory macrophage programming via efferocytosis 间充质干细胞在克罗恩病模型中通过渗出性巨噬细胞持续抗炎程序调节长期疗效

IF 7.2 1区医学

npj Regenerative Medicine Pub Date : 2024-01-20 DOI: 10.1038/s41536-024-00347-1

Maneesh Dave, Atul Dev, Rodrigo A. Somoza, Nan Zhao, Satish Viswanath, Pooja Rani Mina, Prathyush Chirra, Verena Carola Obmann, Ganapati H. Mahabeleshwar, Paola Menghini, Blythe Durbin-Johnson, Jan Nolta, Christopher Soto, Abdullah Osme, Lam T. Khuat, William J. Murphy, Arnold I. Caplan, Fabio Cominelli

{"title":"MSCs mediate long-term efficacy in a Crohn’s disease model by sustained anti-inflammatory macrophage programming via efferocytosis","authors":"Maneesh Dave, Atul Dev, Rodrigo A. Somoza, Nan Zhao, Satish Viswanath, Pooja Rani Mina, Prathyush Chirra, Verena Carola Obmann, Ganapati H. Mahabeleshwar, Paola Menghini, Blythe Durbin-Johnson, Jan Nolta, Christopher Soto, Abdullah Osme, Lam T. Khuat, William J. Murphy, Arnold I. Caplan, Fabio Cominelli","doi":"10.1038/s41536-024-00347-1","DOIUrl":"https://doi.org/10.1038/s41536-024-00347-1","url":null,"abstract":"Mesenchymal stem cells (MSCs) are novel therapeutics for the treatment of Crohn’s disease. However, their mechanism of action is unclear, especially in disease-relevant chronic models of inflammation. Thus, we used SAMP-1/YitFc (SAMP), a chronic and spontaneous murine model of small intestinal inflammation, to study the therapeutic effects and mechanism of action of human bone marrow-derived MSCs (hMSC). hMSC dose-dependently inhibited naïve T lymphocyte proliferation via prostaglandin E2 (PGE2) secretion and reprogrammed macrophages to an anti-inflammatory phenotype. We found that the hMSCs promoted mucosal healing and immunologic response early after administration in SAMP when live hMSCs are present (until day 9) and resulted in a complete response characterized by mucosal, histological, immunologic, and radiological healing by day 28 when no live hMSCs are present. hMSCs mediate their effect via modulation of T cells and macrophages in the mesentery and mesenteric lymph nodes (mLN). Sc-RNAseq confirmed the anti-inflammatory phenotype of macrophages and identified macrophage efferocytosis of apoptotic hMSCs as a mechanism that explains their long-term efficacy. Taken together, our findings show that hMSCs result in healing and tissue regeneration in a chronic model of small intestinal inflammation and despite being short-lived, exert long-term effects via sustained anti-inflammatory programming of macrophages via efferocytosis.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"14 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2024-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139508938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

hUC-MSCs-derived MFGE8 ameliorates locomotor dysfunction via inhibition of ITGB3/ NF-κB signaling in an NMO mouse model. 通过抑制 ITGB3/ NF-κB 信号传导，源自 hUC 间充质干细胞的 MFGE8 可改善 NMO 小鼠模型的运动功能障碍。

IF 7.2 1区医学

npj Regenerative Medicine Pub Date : 2024-01-20 DOI: 10.1038/s41536-024-00349-z

Huiming Xu, Wei Jiang, Xuejia Li, Jiaohua Jiang, Shabbir Khan Afridi, Longhui Deng, Rui Li, Ermei Luo, Zhaoqing Zhang, Yu-Wen Alvin Huang, Yaxiong Cui, Kwok-Fai So, Haijia Chen, Wei Qiu, Changyong Tang

{"title":"hUC-MSCs-derived MFGE8 ameliorates locomotor dysfunction via inhibition of ITGB3/ NF-κB signaling in an NMO mouse model.","authors":"Huiming Xu, Wei Jiang, Xuejia Li, Jiaohua Jiang, Shabbir Khan Afridi, Longhui Deng, Rui Li, Ermei Luo, Zhaoqing Zhang, Yu-Wen Alvin Huang, Yaxiong Cui, Kwok-Fai So, Haijia Chen, Wei Qiu, Changyong Tang","doi":"10.1038/s41536-024-00349-z","DOIUrl":"10.1038/s41536-024-00349-z","url":null,"abstract":"Neuromyelitis optica (NMO) is a severe autoimmune inflammatory disease of the central nervous system that affects motor function and causes relapsing disability. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have been used extensively in the treatment of various inflammatory diseases, due to their potent regulatory roles that can mitigate inflammation and repair damaged tissues. However, their use in NMO is currently limited, and the mechanism underlying the beneficial effects of hUC-MSCs on motor function in NMO remains unclear. In this study, we investigate the effects of hUC-MSCs on the recovery of motor function in an NMO systemic model. Our findings demonstrate that milk fat globule epidermal growth 8 (MFGE8), a key functional factor secreted by hUC-MSCs, plays a critical role in ameliorating motor impairments. We also elucidate that the MFGE8/Integrin αvβ3/NF-κB signaling pathway is partially responsible for structural and functional recovery, in addition to motor functional enhancements induced by hUC-MSC exposure. Taken together, these findings strongly support the involvement of MFGE8 in mediating hUC-MSCs-induced improvements in motor functional recovery in an NMO mouse model. In addition, this provides new insight on the therapeutic potential of hUC-MSCs and the mechanisms underlying their beneficial effects in NMO.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"9 1","pages":"4"},"PeriodicalIF":7.2,"publicationDate":"2024-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10798960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139503233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Engineered extracellular vesicle-encapsulated CHIP as novel nanotherapeutics for treatment of renal fibrosis 将细胞外囊泡包裹的 CHIP 作为治疗肾脏纤维化的新型纳米疗法

IF 7.2 1区医学

npj Regenerative Medicine Pub Date : 2024-01-13 DOI: 10.1038/s41536-024-00348-0

Cheng Ji, Jiahui Zhang, Linru Shi, Hui Shi, Wenrong Xu, Jianhua Jin, Hui Qian

引用次数: 0

Airway epithelial cell identity and plasticity are constrained by Sox2 during lung homeostasis, tissue regeneration, and in human disease 在肺稳态、组织再生和人类疾病过程中，气道上皮细胞的特性和可塑性受制于 Sox2

IF 7.2 1区医学

npj Regenerative Medicine Pub Date : 2024-01-05 DOI: 10.1038/s41536-023-00344-w

Kazushige Shiraishi, Michael P. Morley, Dakota L. Jones, Gan Zhao, Aaron I. Weiner, Maria C. Basil, Edward Cantu, Laura T. Ferguson, Michele Oyster, Apoorva Babu, Yun Ying, Su Zhou, Shanru Li, Andrew E. Vaughan, Edward E. Morrisey

{"title":"Airway epithelial cell identity and plasticity are constrained by Sox2 during lung homeostasis, tissue regeneration, and in human disease","authors":"Kazushige Shiraishi, Michael P. Morley, Dakota L. Jones, Gan Zhao, Aaron I. Weiner, Maria C. Basil, Edward Cantu, Laura T. Ferguson, Michele Oyster, Apoorva Babu, Yun Ying, Su Zhou, Shanru Li, Andrew E. Vaughan, Edward E. Morrisey","doi":"10.1038/s41536-023-00344-w","DOIUrl":"https://doi.org/10.1038/s41536-023-00344-w","url":null,"abstract":"Maintenance of the cellular boundary between airway and alveolar compartments during homeostasis and after injury is essential to prohibit pathological plasticity which can reduce respiratory function. Lung injury and disease can induce either functional alveolar epithelial regeneration or dysplastic formation of keratinized epithelium which does not efficiently contribute to gas exchange. Here we show that Sox2 preserves airway cell identity and prevents fate changes into either functional alveolar tissue or pathological keratinization following lung injury. Loss of Sox2 in airway epithelium leads to a loss of airway epithelial identity with a commensurate gain in alveolar and basal cell identity, in part due to activation of Wnt signaling in secretory cells and increased Trp63 expression in intrapulmonary basal-like progenitors. In idiopathic pulmonary fibrosis, loss of SOX2 expression correlates with increased WNT signaling activity in dysplastic keratinized epithelium. SOX2-deficient dysplastic epithelial cells are also observed in COVID-19 damaged lungs. Thus, Sox2 provides a molecular barrier that suppresses airway epithelial plasticity to prevent acquisition of alveolar or basal cell identity after injury and help guide proper epithelial fate and regeneration.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"61 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139101874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Myeloid cell-associated aromatic amino acid metabolism facilitates CNS myelin regeneration. 髓系细胞相关芳香族氨基酸代谢促进中枢神经系统髓鞘再生

IF 6.4 1区医学

npj Regenerative Medicine Pub Date : 2024-01-02 DOI: 10.1038/s41536-023-00345-9

Jingwen Hu, George S Melchor, Dimitrios Ladakis, Joan Reger, Hee Won Kim, Kelly A Chamberlain, Nataliia V Shults, Helena C Oft, Victoria N Smith, Lauren M Rosko, Erqiu Li, Maryna Baydyuk, Meng-Meng Fu, Pavan Bhargava, Jeffrey K Huang

{"title":"Myeloid cell-associated aromatic amino acid metabolism facilitates CNS myelin regeneration.","authors":"Jingwen Hu, George S Melchor, Dimitrios Ladakis, Joan Reger, Hee Won Kim, Kelly A Chamberlain, Nataliia V Shults, Helena C Oft, Victoria N Smith, Lauren M Rosko, Erqiu Li, Maryna Baydyuk, Meng-Meng Fu, Pavan Bhargava, Jeffrey K Huang","doi":"10.1038/s41536-023-00345-9","DOIUrl":"10.1038/s41536-023-00345-9","url":null,"abstract":"Regulation of myeloid cell activity is critical for successful myelin regeneration (remyelination) in demyelinating diseases, such as multiple sclerosis (MS). Here, we show aromatic alpha-keto acids (AKAs) generated from the amino acid oxidase, interleukin-4 induced 1 (IL4I1), promote efficient remyelination in mouse models of MS. During remyelination, myeloid cells upregulated the expression of IL4I1. Conditionally knocking out IL4I1 in myeloid cells impaired remyelination efficiency. Mice lacking IL4I1 expression exhibited a reduction in the AKAs, phenylpyruvate, indole-3-pyruvate, and 4-hydroxyphenylpyruvate, in remyelinating lesions. Decreased AKA levels were also observed in people with MS, particularly in the progressive phase when remyelination is impaired. Oral administration of AKAs modulated myeloid cell-associated inflammation, promoted oligodendrocyte maturation, and enhanced remyelination in mice with focal demyelinated lesions. Transcriptomic analysis revealed AKA treatment induced a shift in metabolic pathways in myeloid cells and upregulated aryl hydrocarbon receptor activity in lesions. Our results suggest myeloid cell-associated aromatic amino acid metabolism via IL4I1 produces AKAs in demyelinated lesions to enable efficient remyelination. Increasing AKA levels or targeting related pathways may serve as a strategy to facilitate the regeneration of myelin in inflammatory demyelinating conditions.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"9 1","pages":"1"},"PeriodicalIF":6.4,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139089365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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