npj Regenerative Medicine最新文献_第9页

A short dasatinib and quercetin treatment is sufficient to reinstate potent adult neuroregenesis in the aged killifish. 短期达沙替尼和槲皮素治疗足以恢复年老鳉鱼的成年神经再生。

IF 7.2 1区医学

npj Regenerative Medicine Pub Date : 2023-06-16 DOI: 10.1038/s41536-023-00304-4

Jolien Van Houcke, Valerie Mariën, Caroline Zandecki, Rajagopal Ayana, Elise Pepermans, Kurt Boonen, Eve Seuntjens, Geert Baggerman, Lutgarde Arckens

{"title":"A short dasatinib and quercetin treatment is sufficient to reinstate potent adult neuroregenesis in the aged killifish.","authors":"Jolien Van Houcke, Valerie Mariën, Caroline Zandecki, Rajagopal Ayana, Elise Pepermans, Kurt Boonen, Eve Seuntjens, Geert Baggerman, Lutgarde Arckens","doi":"10.1038/s41536-023-00304-4","DOIUrl":"https://doi.org/10.1038/s41536-023-00304-4","url":null,"abstract":"The young African turquoise killifish has a high regenerative capacity, but loses it with advancing age, adopting several aspects of the limited form of mammalian regeneration. We deployed a proteomic strategy to identify pathways that underpin the loss of regenerative power caused by aging. Cellular senescence stood out as a potential brake on successful neurorepair. We applied the senolytic cocktail Dasatinib and Quercetin (D + Q) to test clearance of chronic senescent cells from the aged killifish central nervous system (CNS) as well as rebooting the neurogenic output. Our results show that the entire aged killifish telencephalon holds a very high senescent cell burden, including the parenchyma and the neurogenic niches, which could be diminished by a short-term, late-onset D + Q treatment. Reactive proliferation of non-glial progenitors increased substantially and lead to restorative neurogenesis after traumatic brain injury. Our results provide a cellular mechanism for age-related regeneration resilience and a proof-of-concept of a potential therapy to revive the neurogenic potential in an already aged or diseased CNS.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"8 1","pages":"31"},"PeriodicalIF":7.2,"publicationDate":"2023-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10275874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9657078","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: 1

The one-step fabrication of porous hASC-laden GelMa constructs using a handheld printing system. 利用手持式打印系统一步制备多孔hasc负载的GelMa结构。

IF 7.2 1区医学

npj Regenerative Medicine Pub Date : 2023-06-10 DOI: 10.1038/s41536-023-00307-1

SeoYul Jo, JiUn Lee, Hyeongjin Lee, Dongryeol Ryu, GeunHyung Kim

{"title":"The one-step fabrication of porous hASC-laden GelMa constructs using a handheld printing system.","authors":"SeoYul Jo, JiUn Lee, Hyeongjin Lee, Dongryeol Ryu, GeunHyung Kim","doi":"10.1038/s41536-023-00307-1","DOIUrl":"https://doi.org/10.1038/s41536-023-00307-1","url":null,"abstract":"The fabrication of highly porous cell-loaded structures in tissue engineering applications has been a challenging issue because non-porous cell-laden struts can cause severe cell necrosis in the middle region owing to poor transport of nutrients and oxygen. In this study, we propose a versatile handheld 3D printer for the effective fabrication of porous cell-laden methacrylated gelatin (GelMa) with high porosity (≈97%) by air injection and a bubble-making system using mesh filters through which a mixture of air/GelMa bioink is passed. In particular, the pore size and foamability of the cell constructs could be manipulated using various processing parameters (rheological properties of GelMa, filter size and number, and air-bioink volume ratio). To demonstrate the feasibility of the cell construct as a tissue engineering substitute for muscle regeneration, in vitro cellular activities and in vivo regeneration ability of human adipose stem cells were assessed. The in vitro results demonstrated that the human adipose stem cells (hASCs) fabricated using the handheld 3D printer were alive and well-proliferated. Furthermore, the in vivo results showed that the hASCs-constructs directly printed from the handheld 3D printer showed significant restoration of functionality and efficient muscle regeneration in the volumetric muscle loss model of mice. Based on these results, the fabrication method of the porous cell-laden construct could be a promising tool for regenerating muscle tissues.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"8 1","pages":"30"},"PeriodicalIF":7.2,"publicationDate":"2023-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10257650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9619805","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: 3

DNA methyltransferase 1 deficiency improves macrophage motility and wound healing by ameliorating cholesterol accumulation. DNA甲基转移酶1缺乏通过改善胆固醇积累改善巨噬细胞运动和伤口愈合。

IF 7.2 1区医学

npj Regenerative Medicine Pub Date : 2023-06-08 DOI: 10.1038/s41536-023-00306-2

Chuanrong Zhao, Qianru Yang, Runze Tang, Wang Li, Jin Wang, Fangfang Yang, Jianan Zhao, Juanjuan Zhu, Wei Pang, Ning Li, Xu Zhang, Xiao Yu Tian, Weijuan Yao, Jing Zhou

{"title":"DNA methyltransferase 1 deficiency improves macrophage motility and wound healing by ameliorating cholesterol accumulation.","authors":"Chuanrong Zhao, Qianru Yang, Runze Tang, Wang Li, Jin Wang, Fangfang Yang, Jianan Zhao, Juanjuan Zhu, Wei Pang, Ning Li, Xu Zhang, Xiao Yu Tian, Weijuan Yao, Jing Zhou","doi":"10.1038/s41536-023-00306-2","DOIUrl":"https://doi.org/10.1038/s41536-023-00306-2","url":null,"abstract":"Healing of the cutaneous wound requires macrophage recruitment at the sites of injury, where chemotactic migration of macrophages toward the wound is regulated by local inflammation. Recent studies suggest a positive contribution of DNA methyltransferase 1 (Dnmt1) to macrophage pro-informatory responses; however, its role in regulating macrophage motility remains unknown. In this study, myeloid-specific depletion of Dnmt1 in mice promoted cutaneous wound healing and de-suppressed the lipopolysaccharides (LPS)-inhibited macrophage motility. Dnmt1 inhibition in macrophages eliminated the LPS-stimulated changes in cellular mechanical properties in terms of elasticity and viscoelasticity. LPS increased the cellular accumulation of cholesterol in a Dnmt1-depedent manner; cholesterol content determined cellular stiffness and motility. Lipidomic analysis indicated that Dnmt1 inhibition altered the cellular lipid homeostasis, probably through down-regulating the expression of cluster of differentiation 36 CD36 (facilitating lipid influx) and up-regulating the expression of ATP-binding cassette transporter ABCA1 (mediating lipid efflux) and sterol O-acyltransferase 1 SOAT1 (also named ACAT1, catalyzing the esterification of cholesterol). Our study revealed a Dnmt1-dependent epigenetic mechanism in the control of macrophage mechanical properties and the related chemotactic motility, indicating Dnmt1 as both a marker of diseases and a potential target of therapeutic intervention for wound healing.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"8 1","pages":"29"},"PeriodicalIF":7.2,"publicationDate":"2023-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10250321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9612427","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: 1

Janus porous polylactic acid membranes with versatile metal-phenolic interface for biomimetic periodontal bone regeneration. 具有多功能金属-酚醛界面的聚乳酸多孔膜用于仿生牙周骨再生。

IF 7.2 1区医学

npj Regenerative Medicine Pub Date : 2023-06-03 DOI: 10.1038/s41536-023-00305-3

Yaping Zhang, Yi Chen, Tian Ding, Yandi Zhang, Daiwei Yang, Yajun Zhao, Jin Liu, Baojin Ma, Alberto Bianco, Shaohua Ge, Jianhua Li

{"title":"Janus porous polylactic acid membranes with versatile metal-phenolic interface for biomimetic periodontal bone regeneration.","authors":"Yaping Zhang, Yi Chen, Tian Ding, Yandi Zhang, Daiwei Yang, Yajun Zhao, Jin Liu, Baojin Ma, Alberto Bianco, Shaohua Ge, Jianhua Li","doi":"10.1038/s41536-023-00305-3","DOIUrl":"https://doi.org/10.1038/s41536-023-00305-3","url":null,"abstract":"Conventional treatment to periodontal and many other bone defects requires the use of barrier membranes to guided tissue regeneration (GTR) and guided bone regeneration (GBR). However, current barrier membranes normally lack of the ability to actively regulate the bone repairing process. Herein, we proposed a biomimetic bone tissue engineering strategy enabled by a new type of Janus porous polylactic acid membrane (PLAM), which was fabricated by combining unidirectional evaporation-induced pore formation with subsequent self-assembly of a bioactive metal-phenolic network (MPN) nanointerface. The prepared PLAM-MPN simultaneously possesses barrier function on the dense side and bone-forming function on the porous side. In vitro, the presence of MPN nanointerface potently alleviated the proinflammatory polarization of mice bone marrow-derived macrophages (BMDMs), induced angiogenesis of human umbilical vein endothelial cells (HUVECs), and enhanced the attachment, migration and osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs). The implantation of PLAM-MPN into rat periodontal bone defects remarkably enhanced bone regeneration. This bioactive MPN nanointerface within a Janus porous membrane possesses versatile capacities to regulate cell physiology favoring bone regeneration, demonstrating great potential as GTR and GBR membranes for clinical applications.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"8 1","pages":"28"},"PeriodicalIF":7.2,"publicationDate":"2023-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10239453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9569728","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: 3

Cerebral organoids transplantation repairs infarcted cortex and restores impaired function after stroke. 脑类器官移植修复脑卒中后梗死皮质和恢复受损功能。

IF 7.2 1区医学

npj Regenerative Medicine Pub Date : 2023-05-30 DOI: 10.1038/s41536-023-00301-7

Shi-Ying Cao, Di Yang, Zhen-Quan Huang, Yu-Hui Lin, Hai-Yin Wu, Lei Chang, Chun-Xia Luo, Yun Xu, Yan Liu, Dong-Ya Zhu

{"title":"Cerebral organoids transplantation repairs infarcted cortex and restores impaired function after stroke.","authors":"Shi-Ying Cao, Di Yang, Zhen-Quan Huang, Yu-Hui Lin, Hai-Yin Wu, Lei Chang, Chun-Xia Luo, Yun Xu, Yan Liu, Dong-Ya Zhu","doi":"10.1038/s41536-023-00301-7","DOIUrl":"https://doi.org/10.1038/s41536-023-00301-7","url":null,"abstract":"Stroke usually causes prolonged or lifelong disability, owing to the permanent loss of infarcted tissue. Although a variety of stem cell transplantation has been explored to improve neuronal defect behavior by enhancing neuroplasticity, it remains unknown whether the infarcted tissue can be reconstructed. We here cultured human cerebral organoids derived from human pluripotent stem cells (hPSCs) and transplanted them into the junction of the infarct core and the peri-infarct zone of NOD-SCID mice subjected to stroke. Months later, we found that the grafted organoids survived well in the infarcted core, differentiated into target neurons, repaired infarcted tissue, sent axons to distant brain targets, and integrated into the host neural circuit and thereby eliminated sensorimotor defect behaviors of stroke mice, whereas transplantation of dissociated single cells from organoids failed to repair the infarcted tissue. Our study offers a new strategy for reconstructing infarcted tissue via organoids transplantation thereby reversing stroke-induced disability.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"8 1","pages":"27"},"PeriodicalIF":7.2,"publicationDate":"2023-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10229586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9564946","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: 1

Pluripotent stem cell-derived committed cardiac progenitors remuscularize damaged ischemic hearts and improve their function in pigs. 多能干细胞来源的心脏祖细胞对猪受损的缺血心脏进行再灌注并改善其功能。

IF 7.2 1区医学

npj Regenerative Medicine Pub Date : 2023-05-26 DOI: 10.1038/s41536-023-00302-6

Lynn Yap, Li Yen Chong, Clarissa Tan, Swarnaseetha Adusumalli, Millie Seow, Jing Guo, Zuhua Cai, Sze Jie Loo, Eric Lim, Ru San Tan, Elina Grishina, Poh Loong Soong, Narayan Lath, Lei Ye, Enrico Petretto, Karl Tryggvason

{"title":"Pluripotent stem cell-derived committed cardiac progenitors remuscularize damaged ischemic hearts and improve their function in pigs.","authors":"Lynn Yap, Li Yen Chong, Clarissa Tan, Swarnaseetha Adusumalli, Millie Seow, Jing Guo, Zuhua Cai, Sze Jie Loo, Eric Lim, Ru San Tan, Elina Grishina, Poh Loong Soong, Narayan Lath, Lei Ye, Enrico Petretto, Karl Tryggvason","doi":"10.1038/s41536-023-00302-6","DOIUrl":"https://doi.org/10.1038/s41536-023-00302-6","url":null,"abstract":"Ischemic heart disease, which is often associated with irreversibly damaged heart muscle, is a major global health burden. Here, we report the potential of stem cell-derived committed cardiac progenitors (CCPs) have in regenerative cardiology. Human pluripotent embryonic stem cells were differentiated to CCPs on a laminin 521 + 221 matrix, characterized with bulk and single-cell RNA sequencing, and transplanted into infarcted pig hearts. CCPs differentiated for eleven days expressed a set of genes showing higher expression than cells differentiated for seven days. Functional heart studies revealed significant improvement in left ventricular ejection fraction at four and twelve weeks following transplantation. We also observed significant improvements in ventricular wall thickness and a reduction in infarction size after CCP transplantation (p-value < 0.05). Immunohistology analyses revealed in vivo maturation of the CCPs into cardiomyocytes (CM). We observed temporary episodes of ventricular tachyarrhythmia (VT) in four pigs and persistent VT in one pig, but the remaining five pigs exhibited normal sinus rhythm. Importantly, all pigs survived without the formation of any tumors or VT-related abnormalities. We conclude that pluripotent stem cell-derived CCPs constitute a promising possibility for myocardial infarction treatment and that they may positively impact regenerative cardiology.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"8 1","pages":"26"},"PeriodicalIF":7.2,"publicationDate":"2023-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10219927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9532138","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: 1

A superior extracellular matrix binding motif to enhance the regenerative activity and safety of therapeutic proteins. 一个优越的细胞外基质结合基序，以提高再生活性和治疗蛋白的安全性。

IF 7.2 1区医学

npj Regenerative Medicine Pub Date : 2023-05-22 DOI: 10.1038/s41536-023-00297-0

Yasmin K Alshoubaki, Yen-Zhen Lu, Julien M D Legrand, Rezvan Karami, Mathilde Fossat, Ekaterina Salimova, Ziad Julier, Mikaël M Martino

{"title":"A superior extracellular matrix binding motif to enhance the regenerative activity and safety of therapeutic proteins.","authors":"Yasmin K Alshoubaki, Yen-Zhen Lu, Julien M D Legrand, Rezvan Karami, Mathilde Fossat, Ekaterina Salimova, Ziad Julier, Mikaël M Martino","doi":"10.1038/s41536-023-00297-0","DOIUrl":"https://doi.org/10.1038/s41536-023-00297-0","url":null,"abstract":"Among therapeutic proteins, cytokines and growth factors have great potential for regenerative medicine applications. However, these molecules have encountered limited clinical success due to low effectiveness and major safety concerns, highlighting the need to develop better approaches that increase efficacy and safety. Promising approaches leverage how the extracellular matrix (ECM) controls the activity of these molecules during tissue healing. Using a protein motif screening strategy, we discovered that amphiregulin possesses an exceptionally strong binding motif for ECM components. We used this motif to confer the pro-regenerative therapeutics platelet-derived growth factor-BB (PDGF-BB) and interleukin-1 receptor antagonist (IL-1Ra) a very high affinity to the ECM. In mouse models, the approach considerably extended tissue retention of the engineered therapeutics and reduced leakage in the circulation. Prolonged retention and minimal systemic diffusion of engineered PDGF-BB abolished the tumour growth-promoting adverse effect that was observed with wild-type PDGF-BB. Moreover, engineered PDGF-BB was substantially more effective at promoting diabetic wound healing and regeneration after volumetric muscle loss, compared to wild-type PDGF-BB. Finally, while local or systemic delivery of wild-type IL-1Ra showed minor effects, intramyocardial delivery of engineered IL-1Ra enhanced cardiac repair after myocardial infarction by limiting cardiomyocyte death and fibrosis. This engineering strategy highlights the key importance of exploiting interactions between ECM and therapeutic proteins for developing effective and safer regenerative therapies.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"8 1","pages":"25"},"PeriodicalIF":7.2,"publicationDate":"2023-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10202959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9568908","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: 1

Author Correction: Chondrogenic differentiation induced by extracellular vesicles bound to a nanofibrous substrate. 作者更正:软骨分化是由结合在纳米纤维基质上的细胞外囊泡诱导的。

IF 7.2 1区医学

npj Regenerative Medicine Pub Date : 2023-05-22 DOI: 10.1038/s41536-023-00300-8

Marta R Casanova, Hugo Osório, Rui L Reis, Albino Martins, Nuno M Neves

引用次数: 0

Macrophages maintain mammary stem cell activity and mammary homeostasis via TNF-α-PI3K-Cdk1/Cyclin B1 axis. 巨噬细胞通过TNF-α-PI3K-Cdk1/Cyclin B1轴维持乳腺干细胞活性和乳腺稳态。

IF 7.2 1区医学

npj Regenerative Medicine Pub Date : 2023-05-02 DOI: 10.1038/s41536-023-00296-1

Yu Zhou, Zi Ye, Wei Wei, Mengna Zhang, Fujing Huang, Jinpeng Li, Cheguo Cai

{"title":"Macrophages maintain mammary stem cell activity and mammary homeostasis via TNF-α-PI3K-Cdk1/Cyclin B1 axis.","authors":"Yu Zhou, Zi Ye, Wei Wei, Mengna Zhang, Fujing Huang, Jinpeng Li, Cheguo Cai","doi":"10.1038/s41536-023-00296-1","DOIUrl":"https://doi.org/10.1038/s41536-023-00296-1","url":null,"abstract":"Adult stem cell niche is a special environment composed of a variety stromal cells and signals, which cooperatively regulate tissue development and homeostasis. It is of great interest to study the role of immune cells in niche. Here, we show that mammary resident macrophages regulate mammary epithelium cell division and mammary development through TNF-α-Cdk1/Cyclin B1 axis. In vivo, depletion of macrophages reduces the number of mammary basal cells and mammary stem cells (MaSCs), while increases mammary luminal cells. In vitro, we establish a three-dimensional culture system in which mammary basal cells are co-cultured with macrophages, and interestingly, macrophage co-culture promotes the formation of branched functional mammary organoids. Moreover, TNF-α produced by macrophages activates the intracellular PI3K/Cdk1/Cyclin B1 signaling in mammary cells, thereby maintaining the activity of MaSCs and the formation of mammary organoids. Together, these findings reveal the functional significance of macrophageal niche and intracellular PI3K/Cdk1/Cyclin B1 axis for maintaining MaSC activity and mammary homeostasis.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"8 1","pages":"23"},"PeriodicalIF":7.2,"publicationDate":"2023-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10154328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9411371","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

Rational engineering of lung alveolar epithelium. 肺泡上皮的合理工程。

IF 7.2 1区医学

npj Regenerative Medicine Pub Date : 2023-04-28 DOI: 10.1038/s41536-023-00295-2

Katherine L Leiby, Yifan Yuan, Ronald Ng, Micha Sam Brickman Raredon, Taylor S Adams, Pavlina Baevova, Allison M Greaney, Karen K Hirschi, Stuart G Campbell, Naftali Kaminski, Erica L Herzog, Laura E Niklason

{"title":"Rational engineering of lung alveolar epithelium.","authors":"Katherine L Leiby, Yifan Yuan, Ronald Ng, Micha Sam Brickman Raredon, Taylor S Adams, Pavlina Baevova, Allison M Greaney, Karen K Hirschi, Stuart G Campbell, Naftali Kaminski, Erica L Herzog, Laura E Niklason","doi":"10.1038/s41536-023-00295-2","DOIUrl":"10.1038/s41536-023-00295-2","url":null,"abstract":"Engineered whole lungs may one day expand therapeutic options for patients with end-stage lung disease. However, the feasibility of ex vivo lung regeneration remains limited by the inability to recapitulate mature, functional alveolar epithelium. Here, we modulate multimodal components of the alveolar epithelial type 2 cell (AEC2) niche in decellularized lung scaffolds in order to guide AEC2 behavior for epithelial regeneration. First, endothelial cells coordinate with fibroblasts, in the presence of soluble growth and maturation factors, to promote alveolar scaffold population with surfactant-secreting AEC2s. Subsequent withdrawal of Wnt and FGF agonism synergizes with tidal-magnitude mechanical strain to induce the differentiation of AEC2s to squamous type 1 AECs (AEC1s) in cultured alveoli, in situ. These results outline a rational strategy to engineer an epithelium of AEC2s and AEC1s contained within epithelial-mesenchymal-endothelial alveolar-like units, and highlight the critical interplay amongst cellular, biochemical, and mechanical niche cues within the reconstituting alveolus.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"8 1","pages":"22"},"PeriodicalIF":7.2,"publicationDate":"2023-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10147714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10138870","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