npj Regenerative Medicine最新文献_第5页

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

Type I collagen and fibromodulin enhance the tenogenic phenotype of hASCs and their potential for tendon regeneration I 型胶原蛋白和纤维二聚体可增强 hASCs 的致腱表型及其肌腱再生潜力

IF 7.2 1区医学

npj Regenerative Medicine Pub Date : 2023-12-14 DOI: 10.1038/s41536-023-00341-z

Tian Tu, Yuan Shi, Boya Zhou, Xiaoyu Wang, Wenjie Zhang, Guangdong Zhou, Xiumei Mo, Wenbo Wang, Jinglei Wu, Wei Liu

{"title":"Type I collagen and fibromodulin enhance the tenogenic phenotype of hASCs and their potential for tendon regeneration","authors":"Tian Tu, Yuan Shi, Boya Zhou, Xiaoyu Wang, Wenjie Zhang, Guangdong Zhou, Xiumei Mo, Wenbo Wang, Jinglei Wu, Wei Liu","doi":"10.1038/s41536-023-00341-z","DOIUrl":"https://doi.org/10.1038/s41536-023-00341-z","url":null,"abstract":"Our previous work demonstrated the tendon-derived extracellular matrix (ECM) extracts as vital niches to specifically direct mesenchymal stem cells towards tenogenic differentiation. This study aims to further define the effective ECM molecules capable of teno-lineage induction on human adipose-derived stem cells (hASCs) and test their function for tendon engineering. By detecting the teno-markers expression levels in hASCs exposed to various substrate coatings, collagen I (COL1) and fibromodulin (FMOD) were identified to be the key molecules as a combination and further employed to the modification of poly(L-lactide-co-ε-caprolactone) electrospun nanoyarns, which showed advantages in inducting seeded hASCs for teno-lineage specific differentiation. Under dynamic mechanical loading, modified scaffold seeded with hASCs formed neo-tendon in vitro at the histological level and formed better tendon tissue in vivo with mature histology and enhanced mechanical properties. Primary mechanistic investigation with RNA sequencing demonstrated that the inductive mechanism of these two molecules for hASCs tenogenic differentiation was directly correlated with positive regulation of peptidase activity, regulation of cell-substrate adhesion and regulation of cytoskeletal organization. These biological processes were potentially affected by LOC101929398/has-miR-197-3p/TENM4 ceRNA regulation axis. In summary, COL1 and FMOD in combination are the major bioactive molecules in tendon ECM for likely directing tenogenic phenotype of hASCs and certainly valuable for hASCs-based tendon engineering.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"237 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138630176","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

Effective protection of photoreceptors using an inflammation-responsive hydrogel to attenuate outer retinal degeneration 利用炎症反应水凝胶有效保护光感受器，减少视网膜外层变性

IF 7.2 1区医学

npj Regenerative Medicine Pub Date : 2023-12-14 DOI: 10.1038/s41536-023-00342-y

Hyerim Kim, Hyeonhee Roh, Sang-Heon Kim, Kangwon Lee, Maesoon Im, Seung Ja Oh

{"title":"Effective protection of photoreceptors using an inflammation-responsive hydrogel to attenuate outer retinal degeneration","authors":"Hyerim Kim, Hyeonhee Roh, Sang-Heon Kim, Kangwon Lee, Maesoon Im, Seung Ja Oh","doi":"10.1038/s41536-023-00342-y","DOIUrl":"https://doi.org/10.1038/s41536-023-00342-y","url":null,"abstract":"Retinitis pigmentosa (RP) is an outer retinal degenerative disease that can lead to photoreceptor cell death and profound vision loss. Although effective regulation of intraretinal inflammation can slow down the progression of the disease, an efficient anti-inflammatory treatment strategy is still lacking. This study reports the fabrication of a hyaluronic acid-based inflammation-responsive hydrogel (IRH) and its epigenetic regulation effects on retinal degeneration. The injectable IRH was designed to respond to cathepsin overexpression in an inflammatory environment. The epigenetic drug, the enhancer of zeste homolog 2 (EZH2) inhibitors, was loaded into the hydrogel to attenuate inflammatory factors. On-demand anti-inflammatory effects of microglia cells via the drug-loaded IRH were verified in vitro and in vivo retinal degeneration 10 (rd10) mice model. Therefore, our IRH not only reduced intraretinal inflammation but also protected photoreceptors morphologically and functionally. Our results suggest the IRH reported here can be used to considerably delay vision loss caused by RP.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"23 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138681776","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

Harnessing bioengineered myeloid progenitors for precision immunotherapies 利用生物工程髓系祖细胞进行精准免疫治疗

IF 7.2 1区医学

npj Regenerative Medicine Pub Date : 2023-12-12 DOI: 10.1038/s41536-023-00343-x

Willem Buys, Elias T. Zambidis

{"title":"Harnessing bioengineered myeloid progenitors for precision immunotherapies","authors":"Willem Buys, Elias T. Zambidis","doi":"10.1038/s41536-023-00343-x","DOIUrl":"https://doi.org/10.1038/s41536-023-00343-x","url":null,"abstract":"Granulocytes and macrophages are the frontline defenders of the innate immune system. These myeloid cells play a crucial role in not only eliminating pathogens and tumor cells, but also regulating adaptive immune responses. In neonatal sepsis and post-chemotherapy agranulocytosis, the absence of these cells leaves the host highly vulnerable to infections. Beyond replacement to prevent or control neutropenic sepsis, engineered myeloid cells may offer distinct opportunities for cell therapies. For example, the mobility and specific homing capacities of neutrophils to sites of inflammation could be exploited to deliver biocidal agents, or anti-inflammatory healing signals during sepsis, autoimmunity, and organ transplantation. Additionally, myeloid cells can be engineered to express chimeric antigen receptors (CAR), carry chemotherapeutics, or enhance lymphoid tumor killing. However, traditional methods of cell isolation are incapable of providing sufficient cell numbers of these short-lived cells; their propensity for premature activation further complicates their cell engineering. Here, we review current and future biotherapeutic innovations that employ engineered multipotent myeloid progenitors derived from either self-renewing human induced pluripotent stem cells (hiPSC) or primary CD34+ hematopoietic stem-progenitors. We provide a roadmap for solving the challenges of sourcing, cost, and production of engineered myeloid cell therapies.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"4 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138630186","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

Epidermal-dermal coupled spheroids are important for tissue pattern regeneration in reconstituted skin explant cultures. 表皮-真皮偶联球体是重建皮肤外植体培养中组织模式再生的重要因素。

IF 7.2 1区医学

npj Regenerative Medicine Pub Date : 2023-11-23 DOI: 10.1038/s41536-023-00340-0

Mingxing Lei, Jingwei Jiang, Mengyue Wang, Wang Wu, Jinwei Zhang, Wanqian Liu, Wei Zhou, Yung-Chih Lai, Ting-Xin Jiang, Randall B Widelitz, Hans I-Chen Harn, Li Yang, Cheng-Ming Chuong

{"title":"Epidermal-dermal coupled spheroids are important for tissue pattern regeneration in reconstituted skin explant cultures.","authors":"Mingxing Lei, Jingwei Jiang, Mengyue Wang, Wang Wu, Jinwei Zhang, Wanqian Liu, Wei Zhou, Yung-Chih Lai, Ting-Xin Jiang, Randall B Widelitz, Hans I-Chen Harn, Li Yang, Cheng-Ming Chuong","doi":"10.1038/s41536-023-00340-0","DOIUrl":"10.1038/s41536-023-00340-0","url":null,"abstract":"Tissue patterning is critical for the development and regeneration of organs. To advance the use of engineered reconstituted skin organs, we study cardinal features important for tissue patterning and hair regeneration. We find they spontaneously form spheroid configurations, with polarized epidermal cells coupled with dermal cells through a newly formed basement membrane. Functionally, the spheroid becomes competent morphogenetic units (CMU) that promote regeneration of tissue patterns. The emergence of new cell types and molecular interactions during CMU formation was analyzed using scRNA-sequencing. Surprisingly, in newborn skin explants, IFNr signaling can induce apical-basal polarity in epidermal cell aggregates. Dermal-Tgfb induces basement membrane formation. Meanwhile, VEGF signaling mediates dermal cell attachment to the epidermal cyst shell, thus forming a CMU. Adult mouse and human fetal scalp cells fail to form a CMU but can be restored by adding IFNr or VEGF to achieve hair regeneration. We find different multi-cellular configurations and molecular pathways are used to achieve morphogenetic competence in developing skin, wound-induced hair neogenesis, and reconstituted explant cultures. Thus, multiple paths can be used to achieve tissue patterning. These insights encourage more studies of \"in vitro morphogenesis\" which may provide novel strategies to enhance regeneration.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"8 1","pages":"65"},"PeriodicalIF":7.2,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10667216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138300578","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

Aryl hydrocarbon receptor regulates IL-22 receptor expression on thymic epithelial cell and accelerates thymus regeneration. 芳香烃受体调节胸腺上皮细胞IL-22受体的表达，加速胸腺再生。

IF 7.2 1区医学

npj Regenerative Medicine Pub Date : 2023-11-08 DOI: 10.1038/s41536-023-00339-7

Jingyi Shen, Ying Wang, Fei Zheng, Shuo Cao, Qiu Lan, Kailin Xu, Bin Pan

{"title":"Aryl hydrocarbon receptor regulates IL-22 receptor expression on thymic epithelial cell and accelerates thymus regeneration.","authors":"Jingyi Shen, Ying Wang, Fei Zheng, Shuo Cao, Qiu Lan, Kailin Xu, Bin Pan","doi":"10.1038/s41536-023-00339-7","DOIUrl":"10.1038/s41536-023-00339-7","url":null,"abstract":"Improving regeneration of damaged thymus is important for reconstituting T-cell immunity. Interleukin-22 (IL-22) was proved to improve thymus regeneration through recovering thymic epithelial cells (TECs). The IL-22 receptor IL-22RA1 is crucial for mediating IL-22 functions. Mechanism that regulates IL-22RA1 expression is unknown. Through using TECs-conditional knockout mice, we found aryl hydrocarbon receptor (AHR) is important for thymus regeneration, because Foxn1-cre-mediated AHR knockout (AhrKO) significantly blocks recovery of thymus cells. Giving mice the AHR inhibitor CH-223191 or the AHR agonist FICZ blocks or accelerates thymus regeneration, respectively. AhrKO-mediated blockade of thymus regeneration could not be rescued by giving exogenous IL-22. Mechanistically, AhrKO mice shows decreased IL-22RA1 expression. In the murine TECs cell line mTEC1 cells, targeting AHR shows an impact on IL-22RA1 mRNA levels. Using chromatin immunoprecipitation and luciferase reporter assays, we find AHR co-operates with STAT3, binds the promotor region of IL-22RA1 gene and transcriptionally increases IL-22RA1 expression in mTEC1 cells. Foxn1-cre-mediated IL-22RA1 knockout (Il22ra1KO) blocks thymus regeneration after irradiation. Furthermore, targeting AHR or IL-22RA1 has significant impacts on severity of murine chronic graft-versus-host disease (cGVHD), which is an autoimmune-like complication following allogeneic hematopoietic cell transplantation. Giving FICZ decreases cGVHD, whereas Il22ra1KO exacerbates cGVHD. The impacts on cGVHD are associated with thymus regeneration and T-cell immune reconstitution. In conclusion, we report an unrecognized function of TECs-expressed AHR in thymus regeneration and AHR transcriptionally regulates IL-22RA1 expression, which have implications for improving thymus regeneration and controlling cGVHD.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"8 1","pages":"64"},"PeriodicalIF":7.2,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10632505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71488902","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

Mfap4: a promising target for enhanced liver regeneration and chronic liver disease treatment. Mfap4：增强肝脏再生和治疗慢性肝病的有前景的靶点。

IF 7.2 1区医学

npj Regenerative Medicine Pub Date : 2023-11-07 DOI: 10.1038/s41536-023-00337-9

Viktoriia Iakovleva, Anna Wuestefeld, Agnes Bee Leng Ong, Rong Gao, Neslihan Arife Kaya, May Yin Lee, Weiwei Zhai, Wai Leong Tam, Yock Young Dan, Torsten Wuestefeld

引用次数: 0

Author Correction: Topically-applied collagen-binding serum albumin-fused interleukin-4 modulates wound microenvironment in non-healing wounds. 作者更正：局部应用胶原结合血清白蛋白融合白细胞介素-4调节未愈合伤口的伤口微环境。

IF 7.2 1区医学

npj Regenerative Medicine Pub Date : 2023-11-02 DOI: 10.1038/s41536-023-00338-8

Abigail L Lauterbach, Rachel P Wallace, Aaron T Alpar, Kirsten C Refvik, Joseph W Reda, Ako Ishihara, Taryn N Beckman, Anna J Slezak, Yukari Mizukami, Aslan Mansurov, Suzana Gomes, Jun Ishihara, Jeffrey A Hubbell

引用次数: 0