{"title":"Augmented effect of fibroblast growth factor 18 in bone morphogenetic protein 2-induced calvarial bone healing by activation of CCL2/CCR2 axis on M2 macrophage polarization.","authors":"Worachat Namangkalakul, Shigenori Nagai, Chengxue Jin, Ken-Ichi Nakahama, Yuki Yoshimoto, Satoshi Ueha, Kazunari Akiyoshi, Kouji Matsushima, Tomoki Nakashima, Masaki Takechi, Sachiko Iseki","doi":"10.1177/20417314231187960","DOIUrl":"https://doi.org/10.1177/20417314231187960","url":null,"abstract":"<p><p>Fibroblast growth factor (FGF) signaling plays essential roles in various biological events. FGF18 is one of the ligands to be associated with osteogenesis, chondrogenesis and bone healing. The mouse critical-sized calvarial defect healing induced by the bone morphogenetic protein 2 (BMP2)-hydrogel is stabilized when FGF18 is added. Here, we aimed to investigate the role of FGF18 in the calvarial bone healing model. We first found that FGF18 + BMP2 hydrogel application to the calvarial bone defect increased the expression of anti-inflammatory markers, including those related to tissue healing M2 macrophage (M2-Mø) prior to mineralized bone formation. The depletion of macrophages with clodronate liposome hindered the FGF18 effect. We then examined how FGF18 induces M2-Mø polarization by using mouse primary bone marrow (BM) cells composed of macrophage precursors and BM stromal cells (BMSCs). In vitro studies demonstrated that FGF18 indirectly induces M2-Mø polarization by affecting BMSCs. Whole transcriptome analysis and neutralizing antibody treatment of BMSC cultured with FGF18 revealed that chemoattractant chemokine (c-c motif) ligand 2 (CCL2) is the major mediator for M2-Mø polarization. Finally, FGF18-augmented activity toward favorable bone healing with BMP2 was diminished in the calvarial defect in <i>Ccr2-</i>deleted mice. Altogether, we suggest a novel role of FGF18 in M2-Mø modulation via stimulation of CCL2 production in calvarial bone healing.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"14 ","pages":"20417314231187960"},"PeriodicalIF":8.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c2/72/10.1177_20417314231187960.PMC10387695.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10304672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jae Wan Suh, Kyoung-Mi Lee, Eun Ae Ko, Dong Suk Yoon, Kwang Hwan Park, Hyun Sil Kim, Jong In Yook, Nam Hee Kim, Jin Woo Lee
{"title":"Promoting angiogenesis and diabetic wound healing through delivery of protein transduction domain-BMP2 formulated nanoparticles with hydrogel.","authors":"Jae Wan Suh, Kyoung-Mi Lee, Eun Ae Ko, Dong Suk Yoon, Kwang Hwan Park, Hyun Sil Kim, Jong In Yook, Nam Hee Kim, Jin Woo Lee","doi":"10.1177/20417314231190641","DOIUrl":"https://doi.org/10.1177/20417314231190641","url":null,"abstract":"<p><p>Decreased angiogenesis contributes to delayed wound healing in diabetic patients. Recombinant human bone morphogenetic protein-2 (rhBMP2) has also been demonstrated to promote angiogenesis. However, the short half-lives of soluble growth factors, including rhBMP2, limit their use in wound-healing applications. To address this limitation, we propose a novel delivery model using a protein transduction domain (PTD) formulated in a lipid nanoparticle (LNP). We aimed to determine whether a gelatin hydrogel dressing loaded with LNP-formulated PTD-BMP2 (LNP-PTD-BMP2) could enhance the angiogenic function of BMP2 and improve diabetic wound healing. In vitro, compared to the control and rhBMP2, LNP-PTD-BMP2 induced greater tube formation in human umbilical vein endothelial cells and increased the cell recruitment capacity of HaCaT cells. We inflicted large, full-thickness back skin wounds on streptozotocin-induced diabetic mice and applied gelatin hydrogel (GH) cross-linked by microbial transglutaminase containing rhBMP2, LNP-PTD-BMP2, or a control to these wounds. Wounds treated with LNP-PTD-BMP2-loaded GH exhibited enhanced wound closure, increased re-epithelialization rates, and higher collagen deposition than those with other treatments. Moreover, LNP-PTD-BMP2-loaded GH treatment resulted in more CD31- and α-SMA-positive cells, indicating greater neovascularization capacity than rhBMP2-loaded GH or GH treatments alone. Furthermore, in vivo near-infrared fluorescence revealed that LNP-PTD-BMP2 has a longer half-life than rhBMP2 and that BMP2 localizes around wounds. In conclusion, LNP-PTD-BMP2-loaded GH is a viable treatment option for diabetic wounds.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"14 ","pages":"20417314231190641"},"PeriodicalIF":8.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/67/f6/10.1177_20417314231190641.PMC10434183.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10305939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
David Xinzheyang Li, Zhiyao Ma, Alexander Ra Szojka, Xiaoyi Lan, Melanie Kunze, Aillette Mulet-Sierra, Lindsey Westover, Adetola B Adesida
{"title":"Non-hypertrophic chondrogenesis of mesenchymal stem cells through mechano-hypoxia programing.","authors":"David Xinzheyang Li, Zhiyao Ma, Alexander Ra Szojka, Xiaoyi Lan, Melanie Kunze, Aillette Mulet-Sierra, Lindsey Westover, Adetola B Adesida","doi":"10.1177/20417314231172574","DOIUrl":"https://doi.org/10.1177/20417314231172574","url":null,"abstract":"<p><p>Cartilage tissue engineering aims to generate functional replacements to treat cartilage defects from damage and osteoarthritis. Human bone marrow-derived mesenchymal stem cells (hBM-MSC) are a promising cell source for making cartilage, but current differentiation protocols require the supplementation of growth factors like TGF-β1 or -β3. This can lead to undesirable hypertrophic differentiation of hBM-MSC that progress to bone. We have found previously that exposing engineered human meniscus tissues to physiologically relevant conditions of the knee (mechanical loading and hypoxia; hence, mechano-hypoxia conditioning) increased the gene expression of hyaline cartilage markers, <i>SOX9</i> and <i>COL2A1</i>, inhibited hypertrophic marker <i>COL10A1</i>, and promoted bulk mechanical property development. Adding further to this protocol, we hypothesize that combined mechano-hypoxia conditioning with TGF-β3 growth factor withdrawal will promote stable, non-hypertrophic chondrogenesis of hBM-MSC embedded in an HA-hydrogel. We found that the combined treatment upregulated many cartilage matrix- and development-related markers while suppressing many hypertrophic- and bone development-related markers. Tissue level assessments with biochemical assays, immunofluorescence, and histochemical staining confirmed the gene expression data. Further, mechanical property development in the dynamic compression treatment shows promise toward generating functional engineered cartilage through more optimized and longer culture conditions. In summary, this study introduced a novel protocol to differentiate hBM-MSC into stable, cartilage-forming cells.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"14 ","pages":"20417314231172574"},"PeriodicalIF":8.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4f/45/10.1177_20417314231172574.PMC10192798.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10350364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shan He, Han Wu, Junqun Huang, Qingyan Li, Zijie Huang, Huangding Wen, Zhiqing Li
{"title":"3-D tissue-engineered epidermis against human primary keratinocytes apoptosis via relieving mitochondrial oxidative stress in wound healing.","authors":"Shan He, Han Wu, Junqun Huang, Qingyan Li, Zijie Huang, Huangding Wen, Zhiqing Li","doi":"10.1177/20417314231163168","DOIUrl":"https://doi.org/10.1177/20417314231163168","url":null,"abstract":"<p><p>The tissue-engineered epidermal (TEE), composed of biocompatible vectors and autogenous functional cells, is a novel strategy to solve the problem of shortage of donor skin sources. The human primary keratinocyte (HPK), the major skin components, are self-evident vital in wound healing and was considered as one of the preferred seed cells for TEEs. Since the process of separating HPKs from the skin triggers a stress state of the cells, achieving its rapid adhesion and proliferation on biomaterials remains challenging. The key to the clinical application is to ensure the normal function of cells while improving the proliferation ability in vitro, and to complete the complex mesenchymal epithelialization to achieve tissue remodeling after vivo implantation. Herein, in order to aid HPKs adhesion and proliferation in vitro and promoting wound healing, we developed a three dimensional collagen scaffold with Y-27632 sustainedly released from the nanoplatform, hollow mesoporous organosilica nanoparticles (HMON). The results showed that the porous structure within the TEE supports the implanted HPKs expanding in a three-dimensional mode to jointly construct the tissue-engineered epidermis in vitro and inhibited the mitochondria-mediated cell apoptosis. It was confirmed that the TEEs with suitable degradation rate could maintain drug release after implantation and could accelerate vascularization of wound base and further revealed the involvement of mesenchymal transformation of transplanted HPKs during skin regeneration in a nude mouse model with full-thickness skin resection. In conclusion, our study highlights the great potential of constructing TEE using a nanoparticle platform for the treatment of large-area skin defects.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"14 ","pages":"20417314231163168"},"PeriodicalIF":8.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/90/c6/10.1177_20417314231163168.PMC10071207.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9276693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Óscar Lecina-Tejero, María Ángeles Pérez, Elena García-Gareta, Carlos Borau
{"title":"The rise of mechanical metamaterials: Auxetic constructs for skin wound healing.","authors":"Óscar Lecina-Tejero, María Ángeles Pérez, Elena García-Gareta, Carlos Borau","doi":"10.1177/20417314231177838","DOIUrl":"https://doi.org/10.1177/20417314231177838","url":null,"abstract":"<p><p>Auxetic materials are known for their unique ability to expand/contract in multiple directions when stretched/compressed. In other words, they exhibit a negative Poisson's ratio, which is usually positive for most of materials. This behavior appears in some biological tissues such as human skin, where it promotes wound healing by providing an enhanced mechanical support and facilitating cell migration. Skin tissue engineering has been a growing research topic in recent years, largely thanks to the rapid development of 3D printing techniques and technologies. The combination of computational studies with rapid manufacturing and tailored designs presents a huge potential for the future of personalized medicine. Overall, this review article provides a comprehensive overview of the current state of research on auxetic constructs for skin healing applications, highlighting the potential of auxetics as a promising treatment option for skin wounds. The article also identifies gaps in the current knowledge and suggests areas for future research. In particular, we discuss the designs, materials, manufacturing techniques, and also the computational and experimental studies on this topic.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"14 ","pages":"20417314231177838"},"PeriodicalIF":8.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/bb/7d/10.1177_20417314231177838.PMC10285607.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10291742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sarah Shafaat, Sabiniano Roman Regueros, Christopher Chapple, Sheila MacNeil, Vanessa Hearnden
{"title":"Estradiol-17β [E<sub>2</sub>] stimulates wound healing in a 3D in vitro tissue-engineered vaginal wound model.","authors":"Sarah Shafaat, Sabiniano Roman Regueros, Christopher Chapple, Sheila MacNeil, Vanessa Hearnden","doi":"10.1177/20417314221149207","DOIUrl":"https://doi.org/10.1177/20417314221149207","url":null,"abstract":"<p><p>Childbirth contributes to common pelvic floor problems requiring reconstructive surgery in postmenopausal women. Our aim was to develop a tissue-engineered vaginal wound model to investigate wound healing and the contribution of estradiol to pelvic tissue repair. Partial thickness scalpel wounds were made in tissue models based on decellularized sheep vaginal matrices cultured with primary sheep vaginal epithelial cells and fibroblasts. Models were cultured at an airliquid interface (ALI) for 3 weeks with and without estradiol-17β [E<sub>2</sub>]. Results showed that E<sub>2</sub> significantly increased wound healing and epithelial maturation. Also, E<sub>2</sub> led to collagen reorganization after only 14 days with collagen fibers more regularly aligned and compactly arranged Additionally, E<sub>2</sub> significantly downregulated α-SMA expression which is involved in fibrotic tissue formation. This model allows one to investigate multiple steps in vaginal wound healing and could be a useful tool in developing therapies for improved tissue healing after reconstructive pelvic floor surgery.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"14 ","pages":"20417314221149207"},"PeriodicalIF":8.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/39/91/10.1177_20417314221149207.PMC9885031.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10642929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Md Shafiullah Shajib, Kathryn Futrega, Rose Ann G Franco, Eamonn McKenna, Bianca Guillesser, Travis J Klein, Ross W Crawford, Michael R Doran
{"title":"Method for manufacture and cryopreservation of cartilage microtissues.","authors":"Md Shafiullah Shajib, Kathryn Futrega, Rose Ann G Franco, Eamonn McKenna, Bianca Guillesser, Travis J Klein, Ross W Crawford, Michael R Doran","doi":"10.1177/20417314231176901","DOIUrl":"https://doi.org/10.1177/20417314231176901","url":null,"abstract":"<p><p>The financial viability of a cell and tissue-engineered therapy may depend on the compatibility of the therapy with mass production and cryopreservation. Herein, we developed a method for the mass production and cryopreservation of 3D cartilage microtissues. Cartilage microtissues were assembled from either 5000 human bone marrow-derived stromal cells (BMSC) or 5000 human articular chondrocytes (ACh) each using a customized microwell platform (the Microwell-mesh). Microtissues rapidly accumulate homogenous cartilage-like extracellular matrix (ECM), making them potentially useful building blocks for cartilage defect repair. Cartilage microtissues were cultured for 5 or 10 days and then cryopreserved in 90% serum plus 10% dimethylsulfoxide (DMSO) or commercial serum-free cryopreservation media. Cell viability was maximized during thawing by incremental dilution of serum to reduce oncotic shock, followed by washing and further culture in serum-free medium. When assessed with live/dead viability dyes, thawed microtissues demonstrated high viability but reduced immediate metabolic activity relative to unfrozen control microtissues. To further assess the functionality of the freeze-thawed microtissues, their capacity to amalgamate into a continuous tissue was assess over a 14 day culture. The amalgamation of microtissues cultured for 5 days was superior to those that had been cultured for 10 days. Critically, the capacity of cryopreserved microtissues to amalgamate into a continuous tissue in a subsequent 14-day culture was not compromised, suggesting that cryopreserved microtissues could amalgamate within a cartilage defect site. The quality ECM was superior when amalgamation was performed in a 2% O<sub>2</sub> atmosphere than a 20% O<sub>2</sub> atmosphere, suggesting that this process may benefit from the limited oxygen microenvironment within a joint. In summary, cryopreservation of cartilage microtissues is a viable option, and this manipulation can be performed without compromising tissue function.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"14 ","pages":"20417314231176901"},"PeriodicalIF":8.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10387698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10649796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Idan Carmon, Shira Kalmus, Anna Zobrab, Michael Alterman, Raphaelle Emram, May Gussarsky, Leonid Kandel, Eli Reich, Nardi Casap, Mona Dvir-Ginzberg
{"title":"Repairing a critical cranial defect using WISP1-pretreated chondrocyte scaffolds.","authors":"Idan Carmon, Shira Kalmus, Anna Zobrab, Michael Alterman, Raphaelle Emram, May Gussarsky, Leonid Kandel, Eli Reich, Nardi Casap, Mona Dvir-Ginzberg","doi":"10.1177/20417314231159740","DOIUrl":"https://doi.org/10.1177/20417314231159740","url":null,"abstract":"<p><p>In cranial flat bone fractures, spontaneous bone repair will occur only when the fracture ends are in close contact. However, in cases wherein bone discontinuity is extensive, surgical interventions are often required. To this end, autologous bone is harvested and surgically integrated into the site of fracture. Here we propose to use cartilage, as an alternative autologous source, to promote cranial fracture repair. The advantage of this approach is the potential reduction in donor site morbidity, likely due to the avascular and aneural nature of cartilage. As a first step we attempted to induce cartilage mineralization in vitro, using micromass primary chondrocyte cultures, incubated with BMP2 and/or WISP1, which were examined histologically following a 3-week culture period. Next, chondrocyte seeded collagen scaffolds were evaluated in vitro for expression profiles and ALP activity. Finally, chondrocyte-seeded collagen scaffolds were implanted in a Lewis rats 8 mm critical calvaria defect model, which was imaged via live CT for 12 weeks until sacrifice. End points were analyzed for microCT, histology, and serum levels of bone related markers. Micromass cultures exhibited an osseous inducing trend following WISP1 administration, which was maintained in chondrocyte seeded scaffolds. Accordingly, in vivo analysis was carried out to assess the impact of WISP1-pretreated chondrocytes (WCS) versus untreated chondrocytes (UCS) in calvaria defect model and compared to untreated control comprised of a defect-associated blood clot (BC) or empty collagen scaffold (CS) implant. Live CT and microCT exhibited higher mineralization volumes in critical defect implanted with UCS, with some structural improvements in WCS. Histological analysis exhibited higher anabolic bone formation in WCS and trabecular bone was detected in WCS and UCS groups. Chondrocytes implanted into critical cranial defect expedite the formation of native-like osseous tissue, especially after WISP1 priming in culture. Ultimately, these data support the use of autologous chondrocytes to repair critical maxillofacial defects.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"14 ","pages":"20417314231159740"},"PeriodicalIF":8.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b7/ee/10.1177_20417314231159740.PMC10026108.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9166696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xingran Liu, Yihao Liu, Lei Qiang, Ya Ren, Yixuan Lin, Han Li, Qiuhan Chen, Shuxin Gao, Xue Yang, Changru Zhang, Minjie Fan, Pengfei Zheng, Shuai Li, Jinwu Wang
{"title":"Multifunctional 3D-printed bioceramic scaffolds: Recent strategies for osteosarcoma treatment.","authors":"Xingran Liu, Yihao Liu, Lei Qiang, Ya Ren, Yixuan Lin, Han Li, Qiuhan Chen, Shuxin Gao, Xue Yang, Changru Zhang, Minjie Fan, Pengfei Zheng, Shuai Li, Jinwu Wang","doi":"10.1177/20417314231170371","DOIUrl":"https://doi.org/10.1177/20417314231170371","url":null,"abstract":"<p><p>Osteosarcoma is the most prevalent bone malignant tumor in children and teenagers. The bone defect, recurrence, and metastasis after surgery severely affect the life quality of patients. Clinically, bone grafts are implanted. Primary bioceramic scaffolds show a monomodal osteogenesis function. With the advances in three-dimensional printing technology and materials science, while maintaining the osteogenesis ability, scaffolds become more patient-specific and obtain additional anti-tumor ability with functional agents being loaded. Anti-tumor therapies include photothermal, magnetothermal, old and novel chemo-, gas, and photodynamic therapy. These strategies kill tumors through novel mechanisms to treat refractory osteosarcoma due to drug resistance, and some have shown the potential to reverse drug resistance and inhibit metastasis. Therefore, multifunctional three-dimensional printed bioceramic scaffolds hold excellent promise for osteosarcoma treatments. To better understand, we review the background of osteosarcoma, primary 3D-printed bioceramic scaffolds, and different therapies and have a prospect for the future.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"14 ","pages":"20417314231170371"},"PeriodicalIF":8.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ce/92/10.1177_20417314231170371.PMC10186582.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10645384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Continuous nutrient supply culture strategy controls multivesicular endosomes pathway and anti-photo-aging miRNA cargo loading of extracellular vesicles.","authors":"Lihao Chen, Weihan Xie, Keke Wu, Yuan Meng, Yijun He, Jiawei Cai, Yuan Jiang, Qi Zhao, Yixi Yang, Minru Zhang, Manping Lu, Shaozhang Lin, Lin Liang, Zhiyong Zhang","doi":"10.1177/20417314231197604","DOIUrl":"https://doi.org/10.1177/20417314231197604","url":null,"abstract":"<p><p>Extracellular vesicle (EV) therapy recently had shown significant efficacy in various diseases. Serum starvation culture (SC) is one of the most widely used methods for collecting EVs. However, SC may cause inadvertent effects and eventually dampen the therapeutic potential of EVs. Therefore, we developed a novel method for EV collection, continuous nutrient supply culture (CC), which can provide an optimal condition for mesenchymal stem cells (MSCs) by continuously supplying essential nutrients to MSCs. By comparing with SC strategy, we revealed that CC could maintain CC-MSCs in a normal autophagy and apoptotic state, which reduced the shunting of EV precursors in cells and useless information material carried by EVs. In CC-MSCs, the expression levels of endosomal sorting complexes required for transport (ESCRT) and targeting GTPase27 (Rab27) were upregulated compared to those in SC-MSCs. Besides, we analyzed the membrane transport efficiency of EV formation, which demonstrated the CC strategy could promote the formation of EV precursors and the release of EVs. In addition, miRNA analysis revealed that CC-EVs were enriched with anti-chronic inflammatory factors, which could inhibit the nuclear factor kappa-B (NF-κB) pathway, mitigate chronic inflammation, and effectively repair skin photo-aging damage.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"14 ","pages":"20417314231197604"},"PeriodicalIF":8.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/65/49/10.1177_20417314231197604.PMC10478562.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10669369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}