{"title":"A review of current status of cell-based therapies for aortic aneurysms.","authors":"Aika Yamawaki-Ogata, Masato Mutsuga, Yuji Narita","doi":"10.1186/s41232-023-00280-8","DOIUrl":"10.1186/s41232-023-00280-8","url":null,"abstract":"<p><p>An aortic aneurysm (AA) is defined as focal aortic dilation that occurs mainly with older age and with chronic inflammation associated with atherosclerosis. The aneurysmal wall is a complex inflammatory environment characterized by endothelial dysfunction, macrophage activation, vascular smooth muscle cell (VSMC) apoptosis, and the production of proinflammatory molecules and matrix metalloproteases (MMPs) secreted by infiltrated inflammatory cells such as macrophages, T and B cells, dendritic cells, neutrophils, mast cells, and natural killer cells. To date, a considerable number of studies have been conducted on stem cell research, and growing evidence indicates that inflammation and tissue repair can be controlled through the functions of stem/progenitor cells. This review summarizes current cell-based therapies for AA, involving mesenchymal stem cells, VSMCs, multilineage-differentiating stress-enduring cells, and anti-inflammatory M2 macrophages. These cells produce beneficial outcomes in AA treatment by modulating the inflammatory environment, including decreasing the activity of proinflammatory molecules and MMPs, increasing anti-inflammatory molecules, modulating VSMC phenotypes, and preserving elastin. This article also describes detailed studies on pathophysiological mechanisms and the current progress of clinical trials.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":null,"pages":null},"PeriodicalIF":8.1,"publicationDate":"2023-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10405412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9959322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Autoimmune-mediated astrocytopathy.","authors":"Makoto Kinoshita, Tatsusada Okuno","doi":"10.1186/s41232-023-00291-5","DOIUrl":"https://doi.org/10.1186/s41232-023-00291-5","url":null,"abstract":"<p><p>Recently accumulating evidence identified the disease entity where astrocytes residing within the central nervous system (CNS) are the target of autoantibody-mediated autoimmunity. Aquaporin4 (AQP4) is the most common antigen to serve as astrocyte-targeted autoimmune responses. Here, in this review, the clinical and pathological aspects of AQP4-mediated astrocyte disease are discussed together with the pathogenic role of anti-AQP4 antibody. More recently, the mechanism of immune dysregulation resulting in the production of astrocyte-targeted autoantibody is also revealed, and the postulated hypothesis is discussed.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":null,"pages":null},"PeriodicalIF":8.1,"publicationDate":"2023-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10353242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9833625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Lipid in microglial biology - from material to mediator.","authors":"Shota Yamamoto, Takahiro Masuda","doi":"10.1186/s41232-023-00289-z","DOIUrl":"https://doi.org/10.1186/s41232-023-00289-z","url":null,"abstract":"<p><p>Microglia are resident macrophages in the central nervous system (CNS) that play various roles during brain development and in the pathogenesis of CNS diseases. Recently, reprogramming of cellular energetic metabolism in microglia has drawn attention as a crucial mechanism for diversification of microglial functionality. Lipids are highly diverse materials and crucial components of cell membranes in every cell. Accumulating evidence has shown that lipid and its metabolism are tightly involved in microglial biology. In this review, we summarize the current knowledge about microglial lipid metabolism in health and disease.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":null,"pages":null},"PeriodicalIF":8.1,"publicationDate":"2023-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10351166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9800753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"ALKBH5-mediated m<sup>6</sup>A demethylation fuels cutaneous wound re-epithelialization by enhancing PELI2 mRNA stability.","authors":"Xin Huang, Yixuan Zhao, Daiming Liu, Shuchen Gu, Yunhan Liu, Yimin Khoong, Shenying Luo, Zewei Zhang, Wenzheng Xia, Meng Wang, Hsin Liang, Minxiong Li, Qingfeng Li, Tao Zan","doi":"10.1186/s41232-023-00288-0","DOIUrl":"https://doi.org/10.1186/s41232-023-00288-0","url":null,"abstract":"<p><strong>Background: </strong>Impaired wound re-epithelialization contributes to cutaneous barrier reconstruction dysfunction. Recently, N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) RNA modification has been shown to participate in the determination of RNA fate, and its aberration triggers the pathogenesis of numerous diseases. Howbeit, the function of m<sup>6</sup>A in wound re-epithelialization remains enigmatic.</p><p><strong>Methods: </strong>Alkbh5<sup>‒/‒</sup> mouse was constructed to study the rate of wound re-epithelialization after ALKBH5 ablation. Integrated high-throughput analysis combining methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-seq was used to identify the downstream target of ALKBH5. In vitro and in vivo rescue experiments were conducted to verify the role of the downstream target on the functional phenotype of ALKBH5-deficient cells or animals. Furthermore, the interacting reader protein and regulatory mechanisms were determined through RIP-qPCR, RNA pull-down, and RNA stability assays.</p><p><strong>Results: </strong>ALKBH5 was specifically upregulated in the wound edge epidermis. Ablation of ALKBH5 suppressed keratinocyte migration and resulted in delayed wound re-epithelialization in Alkbh5<sup>‒/‒</sup> mouse. Integrated high-throughput analysis revealed that PELI2, an E3 ubiquitin protein ligase, serves as the downstream target of ALKBH5. Concordantly, exogenous PELI2 supplementation partially rescued keratinocyte migration and accelerated re-epithelialization in ALKBH5-deficient cells, both in vitro and in vivo. In terms of its mechanism, ALKBH5 promoted PELI2 expression by removing the m<sup>6</sup>A modification from PELI2 mRNA and enhancing its stability in a YTHDF2-dependent manner.</p><p><strong>Conclusions: </strong>This study identifies ALKBH5 as an endogenous accelerator of wound re-epithelialization, thereby benefiting the development of a reprogrammed m<sup>6</sup>A targeted therapy for refractory wounds.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":null,"pages":null},"PeriodicalIF":8.1,"publicationDate":"2023-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10347733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9821534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tian Lan, Yang Tai, Chong Zhao, Yang Xiao, Zhu Yang, Linhao Zhang, Can Gan, Wenting Dai, Huan Tong, Chengwei Tang, Zhiyin Huang, Jinhang Gao
{"title":"Atypical cholangiocytes derived from hepatocyte-cholangiocyte transdifferentiation mediated by COX-2: a kind of misguided liver regeneration.","authors":"Tian Lan, Yang Tai, Chong Zhao, Yang Xiao, Zhu Yang, Linhao Zhang, Can Gan, Wenting Dai, Huan Tong, Chengwei Tang, Zhiyin Huang, Jinhang Gao","doi":"10.1186/s41232-023-00284-4","DOIUrl":"https://doi.org/10.1186/s41232-023-00284-4","url":null,"abstract":"<p><strong>Background: </strong>Hepatocyte-cholangiocyte transdifferentiation (HCT) is a potential origin of proliferating cholangiocytes in liver regeneration after chronic injury. This study aimed to determine HCT after chronic liver injury, verify the impacts of HCT on liver repair, and avoid harmful regeneration by understanding the mechanism.</p><p><strong>Methods: </strong>A thioacetamide (TAA)-induced liver injury model was established in wild-type (WT-TAA group) and COX-2 panknockout (KO-TAA group) mice. HCT was identified by costaining of hepatocyte and cholangiocyte markers in vivo and in isolated mouse hepatocytes in vitro. The biliary tract was injected with ink and visualized by whole liver optical clearing. Serum and liver bile acid (BA) concentrations were measured. Either a COX-2 selective inhibitor or a β-catenin pathway inhibitor was administered in vitro.</p><p><strong>Results: </strong>Intrahepatic ductular reaction was associated with COX-2 upregulation in chronic liver injury. Immunofluorescence and RNA sequencing indicated that atypical cholangiocytes were characterized by an intermediate genetic phenotype between hepatocytes and cholangiocytes and might be derived from hepatocytes. The structure of the biliary system was impaired, and BA metabolism was dysregulated by HCT, which was mediated by the TGF-β/β-catenin signaling pathway. Genetic deletion or pharmaceutical inhibition of COX-2 significantly reduced HCT in vivo. The COX-2 selective inhibitor etoricoxib suppressed HCT through the TGF-β-TGFBR1-β-catenin pathway in vitro.</p><p><strong>Conclusions: </strong>Atypical cholangiocytes can be derived from HCT, which forms a secondary strike by maldevelopment of the bile drainage system and BA homeostasis disequilibrium during chronic liver injury. Inhibition of COX-2 could ameliorate HCT through the COX-2-TGF-β-TGFBR1-β-catenin pathway and improve liver function.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":null,"pages":null},"PeriodicalIF":8.1,"publicationDate":"2023-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10347763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9821535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Min Kyoung Jo, Chang Mo Moon, Hyeon-Jeong Jeon, Yerim Han, Eun Sook Lee, Ji-Hee Kwon, Kyung-Min Yang, Young-Ho Ahn, Seong-Eun Kim, Sung-Ae Jung, Tae Il Kim
{"title":"Effect of aging on the formation and growth of colonic epithelial organoids by changes in cell cycle arrest through TGF-β-Smad3 signaling.","authors":"Min Kyoung Jo, Chang Mo Moon, Hyeon-Jeong Jeon, Yerim Han, Eun Sook Lee, Ji-Hee Kwon, Kyung-Min Yang, Young-Ho Ahn, Seong-Eun Kim, Sung-Ae Jung, Tae Il Kim","doi":"10.1186/s41232-023-00282-6","DOIUrl":"https://doi.org/10.1186/s41232-023-00282-6","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to investigate how aging alters the homeostasis of the colonic intestinal epithelium and regeneration after tissue injury using organoid models and to identify its underlying molecular mechanism.</p><p><strong>Methods: </strong>To investigate aging-related changes in the colonic intestinal epithelium, we conducted organoid cultures from old (older than 80 weeks) and young (6-10 weeks) mice and compared the number and size of organoids at day 5 of passage 0 and the growth rate of organoids between the two groups.</p><p><strong>Results: </strong>The number and size of organoids from old mice was significantly lower than that from young mice (p < 0.0001) at day 5 of passage 0. The growth rate of old-mouse organoids from day 4 to 5 of passage 0 was significantly slower than that of young-mouse organoids (2.21 times vs. 1.16 times, p < 0.001). RNA sequencing showed that TGF-β- and cell cycle-associated genes were associated with the aging effect. With regard to mRNA and protein levels, Smad3 and p-Smad3 in the old-mouse organoids were markedly increased compared with those in the young-mouse organoids. Decreased expression of ID1, increased expression of p16<sup>INK4a</sup>, and increased cell cycle arrest were observed in the old mouse-organoids. Treatment with SB431542, a type I TGF-β receptor inhibitor, significantly increased the formation and growth of old-mouse organoids, and TGF-β1 treatment markedly suppressed the formation of young-mouse organoids. In the acute dextran sulfate sodium-colitis model and its organoid experiments, the colonic epithelial regeneration after tissue injury in old mice was significantly decreased compared with young mice.</p><p><strong>Conclusions: </strong>Aging reduced the formation ability and growth rate of colonic epithelial organoids by increasing cell cycle arrest through TGF-β-Smad3-p16<sup>INK4a</sup> signaling.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":null,"pages":null},"PeriodicalIF":8.1,"publicationDate":"2023-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10339613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9871423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cartilage evaluation by ultrasonography in patients with rheumatoid arthritis: a scoping review.","authors":"Takehisa Ogura, Takaharu Katagiri, Hideto Kameda","doi":"10.1186/s41232-023-00286-2","DOIUrl":"https://doi.org/10.1186/s41232-023-00286-2","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to provide an overview of ultrasonographic cartilage evaluation in patients with rheumatoid arthritis (RA) and identify research gaps in the utilization of cartilage evaluation.</p><p><strong>Methods: </strong>The study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines. A systematic literature search of the PubMed, Embase, and Cochrane Library databases was conducted for articles published up to July 2022 using the search term variations of \"cartilage,\" \"ultrasonography,\" and \"rheumatoid arthritis.\" Studies that included patients with RA who underwent cartilage evaluation by ultrasonography were selected. Articles published in languages other than English and about juvenile idiopathic arthritis were excluded.</p><p><strong>Results: </strong>Twenty-nine articles were identified. Most were cross-sectional studies (86%), mainly involving the metacarpophalangeal (55%) and knee (34%) joints. Assessments were performed using quantitative, binary, and semi-quantitative methods in 15, 10, and 15 studies, respectively. Reliability assessments were conducted in 10 studies, which showed feasible reliability but were limited to the finger joints. The validity assessment was validated in one study each that compared cartilage thickness measurements with cadaveric specimens and histological and semi-quantitative methods with surgical specimens, respectively. Comparisons with conventional radiography were also performed in six studies, which showed significant correlations. However, there was heterogeneity in the examination and assessment methods, and no adequate longitudinal evaluation was conducted.</p><p><strong>Conclusion: </strong>This review highlights the need for further research and validation of ultrasonographic cartilage assessment in patients with RA.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":null,"pages":null},"PeriodicalIF":8.1,"publicationDate":"2023-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10318783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9755974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Stem cell-based drug delivery strategy for skin regeneration and wound healing: potential clinical applications.","authors":"Weiyue Zhang, Xin Huang","doi":"10.1186/s41232-023-00287-1","DOIUrl":"https://doi.org/10.1186/s41232-023-00287-1","url":null,"abstract":"<p><p>Stem cell-based therapy is widely accepted to be a promising strategy in tissue regenerative medicine. Nevertheless, there are several obstacles to applying stem cells in skin regeneration and wound healing, which includes determining the optimum source, the processing and administration methods of stem cells, and the survival and functions of stem cells in wound sites. Owing to the limitations of applying stem cells directly, this review aims to discuss several stem cell-based drug delivery strategies in skin regeneration and wound healing and their potential clinical applications. We introduced diverse types of stem cells and their roles in wound repair. Moreover, the stem cell-based drug delivery systems including stem cell membrane-coated nanoparticles, stem cell-derived extracellular vesicles, stem cell as drug carriers, scaffold-free stem cell sheets, and stem cell-laden scaffolds were further investigated in the field of skin regeneration and wound healing. More importantly, stem cell membrane-coating nanotechnology confers great advantages compared to other drug delivery systems in a broad field of biomedical contexts. Taken together, the stem cell-based drug delivery strategy holds great promise for treating skin regeneration and wound healing.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":null,"pages":null},"PeriodicalIF":8.1,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10311866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9743795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zi-Yuan Zhang, Zhao-Yang Zuo, Yang Liang, Si-Ming Zhang, Chun-Xia Zhang, Jing Chi, Bin Fan, Guang-Yu Li
{"title":"Promotion of axon regeneration and protection on injured retinal ganglion cells by rCXCL2.","authors":"Zi-Yuan Zhang, Zhao-Yang Zuo, Yang Liang, Si-Ming Zhang, Chun-Xia Zhang, Jing Chi, Bin Fan, Guang-Yu Li","doi":"10.1186/s41232-023-00283-5","DOIUrl":"https://doi.org/10.1186/s41232-023-00283-5","url":null,"abstract":"<p><strong>Background: </strong>In addition to rescuing injured retinal ganglion cells (RGCs) by stimulating the intrinsic growth ability of damaged RGCs in various retinal/optic neuropathies, increasing evidence has shown that the external microenvironmental factors also play a crucial role in restoring the survival of RGCs by promoting the regrowth of RGC axons, especially inflammatory factors. In this study, we aimed to screen out the underlying inflammatory factor involved in the signaling of staurosporine (STS)-induced axon regeneration and verify its role in the protection of RGCs and the promotion of axon regrowth.</p><p><strong>Methods: </strong>We performed transcriptome RNA sequencing for STS induction models in vitro and analyzed the differentially expressed genes. After targeting the key gene, we verified the role of the candidate factor in RGC protection and promotion of axon regeneration in vivo with two RGC-injured animal models (optic nerve crush, ONC; retinal N-methyl-D-aspartate, NMDA damage) by using cholera toxin subunit B anterograde axon tracing and specific immunostaining of RGCs.</p><p><strong>Results: </strong>We found that a series of inflammatory genes expressed upregulated in the signaling of STS-induced axon regrowth and we targeted the candidate CXCL2 gene since the level of the chemokine CXCL2 gene elevated significantly among the top upregulated genes. We further demonstrated that intravitreal injection of rCXCL2 robustly promoted axon regeneration and significantly improved RGC survival in ONC-injured mice in vivo. However, different from its role in ONC model, the intravitreal injection of rCXCL2 was able to simply protect RGCs against NMDA-induced excitotoxicity in mouse retina and maintain the long-distance projection of RGC axons, yet failed to promote significant axon regeneration.</p><p><strong>Conclusions: </strong>We provide the first in vivo evidence that CXCL2, as an inflammatory factor, is a key regulator in the axon regeneration and neuroprotection of RGCs. Our comparative study may facilitate deciphering the exact molecular mechanisms of RGC axon regeneration and developing high-potency targeted drugs.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":null,"pages":null},"PeriodicalIF":8.1,"publicationDate":"2023-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10280836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10086066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Enhancement of bone regeneration by coadministration of angiogenic and osteogenic factors using messenger RNA.","authors":"Maorui Zhang, Yuta Fukushima, Kosuke Nozaki, Hideyuki Nakanishi, Jia Deng, Noriyuki Wakabayashi, Keiji Itaka","doi":"10.1186/s41232-023-00285-3","DOIUrl":"https://doi.org/10.1186/s41232-023-00285-3","url":null,"abstract":"<p><strong>Background: </strong>Bone defects remain a challenge today. In addition to osteogenic activation, the crucial role of angiogenesis has also gained attention. In particular, vascular endothelial growth factor (VEGF) is likely to play a significant role in bone regeneration, not only to restore blood supply but also to be directly involved in the osteogenic differentiation of mesenchymal stem cells. In this study, to produce additive angiogenic-osteogenic effects in the process of bone regeneration, VEGF and Runt-related transcription factor 2 (Runx2), an essential transcription factor for osteogenic differentiation, were coadministered with messenger RNAs (mRNAs) to bone defects in the rat mandible.</p><p><strong>Methods: </strong>The mRNAs encoding VEGF or Runx2 were prepared via in vitro transcription (IVT). Osteogenic differentiation after mRNA transfection was evaluated using primary osteoblast-like cells, followed by an evaluation of the gene expression levels of osteogenic markers. The mRNAs were then administered to a bone defect prepared in the rat mandible using our original cationic polymer-based carrier, the polyplex nanomicelle. The bone regeneration was evaluated by micro-computerized tomography (μCT) imaging, and histologic analyses.</p><p><strong>Results: </strong>Osteogenic markers such as osteocalcin (Ocn) and osteopontin (Opn) were significantly upregulated after mRNA transfection. VEGF mRNA was revealed to have a distinct osteoblastic function similar to that of Runx2 mRNA, and the combined use of the two mRNAs resulted in further upregulation of the markers. After in vivo administration into the bone defect, the two mRNAs induced significant enhancement of bone regeneration with increased bone mineralization. Histological analyses using antibodies against the Cluster of Differentiation 31 protein (CD31), alkaline phosphatase (ALP), or OCN revealed that the mRNAs induced the upregulation of osteogenic markers in the defect, together with increased vessel formation, leading to rapid bone formation.</p><p><strong>Conclusions: </strong>These results demonstrate the feasibility of using mRNA medicines to introduce various therapeutic factors, including transcription factors, into target sites. This study provides valuable information for the development of mRNA therapeutics for tissue engineering.</p>","PeriodicalId":13588,"journal":{"name":"Inflammation and Regeneration","volume":null,"pages":null},"PeriodicalIF":8.1,"publicationDate":"2023-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10280834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9712560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}