Restoring tracheal defects in a rabbit model with tissue engineered patches based on TGF-β3-encapsulating electrospun poly(<scp>l</scp>-lactic acid-co-ε-caprolactone)/collagen scaffolds

Jing, Hui; Gao, Botao; Gao, Manchen; Yin, Haiyue; Mo, Xiumei; Zhang, Xiaoyang; Luo, Kai; Feng, Bei; Fu, Wei; Wang, Jing; Zhang, Wei; Yin, Meng; Zhu, Zhongqun; He, Xiaomin; Zheng, Jie

doi:10.1080/21691401.2018.1439844

Cited by 8 publications

(7 citation statements)

References 21 publications

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“…In order to observe the cellular proliferation and adhesion on nanofilms upon implantation, the cellular outlines were delineated by phalloidin, a fluorochrome that could bind specifically with the cytoskeleton, as previously described in Jing et al . (5).…”

Section: Methodsmentioning

confidence: 99%

“…All cell-scaffold constructs were incubated in growth medium for 7 d to guarantee the cellular adhesion and proliferation and then implanted subcutaneously into nude mice (n = 5 in each group) with customized 3D-printed grooved PLCL mold (inner diameter: 6 mm, radial length: 2.5 cm) for maturation in vivo. In order to observe the cellular proliferation and adhesion on nanofilms upon implantation, the cellular outlines were delineated by phalloidin, a fluorochrome that could bind specifically with the cytoskeleton, as previously described in Jing et al (5).…”

Section: Validation Of Beneficial Effects Of Kgn Preconditioning In Vivomentioning

confidence: 99%

“…Most patients with long-segment tracheal stenosis are often confronted with a poor prognosis because of a limitation in the materials available for tracheal reconstruction (2,3). Although emerging tissue-engineered trachea strategies using mesenchymal stem cells (MSCs) could present a successful option for repairing tracheal stenosis (4)(5)(6), their clinical applications are currently controversial. The chondrogenic differentiation of MSCs in vitro is dependent on exogenous induction factors, such as TGF-b and bone morphogenetic protein family members, which can be supplemented in the culture microenvironment (7,8).…”

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confidence: 99%

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Kartogenin preconditioning commits mesenchymal stem cells to a precartilaginous stage with enhanced chondrogenic potential by modulating JNK and β‐catenin–related pathways

et al. 2019

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Cartilage engineering strategies using mesenchymal stem cells (MSCs) could provide preferable solutions to resolve long‐segment tracheal defects. However, the drawbacks of widely used chondrogenic protocols containing TGF‐β3, such as inefficiency and unstable cellular phenotype, are problematic. In our research, to optimize the chondrogenic differentiation of human umbilical cord MSCs (hUCMSCs), kartogenin (KGN) preconditioning was performed prior to TGF‐β3 induction. hUCMSCs were preconditioned with 1 µM of KGN for 3 d, sequentially pelleted, and incubated with TGF‐β3 for 28 d. Then, the expression of chondrogenesis‐ and ossification‐related genes was evaluated by immunohistochemistry and RT‐PCR. The underlying mechanism governing the beneficial effects of KGN preconditioning was explored by phosphorylated kinase screening and validated in vitro and in vivo using JNK inhibitor (SP600125) and β‐catenin activator (SKL2001). After KGN preconditioning, expression of fibroblast growth factor receptor 3, a marker of precartilaginous stem cells, was up‐regulated in hUCMSCs. Furthermore, the KGN‐preconditioned hUCMSCs efficiently differentiated into chondrocytes with elevated chondrogenic gene (SOX9, aggrecan, and collagen II) expression and reduced expression of ossifie genes (collagen X and MMP13) compared with hUCMSCs treated with TGF‐β3 only. Phosphokinase screening indicated that the beneficial effects of KGN preconditioning are directly related to an up‐regulation of JNK phosphorylation and a suppression of β‐catenin levels. Blocking and activating tests revealed that the prochondrogenic effects of KGN preconditioning was achieved mainly by activating the JNK/Runt‐related transcription factor (RUNX)1 pathway, and antiossific effects were imparted by suppressing the β‐catenin/RUNX2 pathway. Eventually, tracheal patches, based on KGN‐preconditioned hUCMSCs and TGF‐β3 encapsulated electrospun poly (l‐lactic acid‐co‐ε‐caprolactone)/collagen nanofilms, were successfully used for restoring tracheal defects in rabbit models. In summary, KGN preconditioning likely improves the chondrogenic differentiation of hUCMSCs by committing them to a precartilaginous stage with enhanced JNK phosphorylation and suppressed β‐catenin. This novel protocol consisting of KGN preconditioning and subsequent TGF‐β3 induction might be preferable for cartilage engineering strategies using MSCs.—Jing, H., Zhang, X., Gao, M., Luo, K., Fu, W., Yin, M., Wang, W., Zhu, Z., Zheng, J., He, X. Kartogenin preconditioning commits mesenchymal stem cells to a precartilaginous stage with enhanced chondrogenic potential by modulating JNK and β‐catenin—related pathways. FASEB J. 33, 5641–5653 (2019). http://www.fasebj.org

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Section: Methodsmentioning

confidence: 99%

Section: Validation Of Beneficial Effects Of Kgn Preconditioning In Vivomentioning

confidence: 99%

mentioning

confidence: 99%

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Kartogenin preconditioning commits mesenchymal stem cells to a precartilaginous stage with enhanced chondrogenic potential by modulating JNK and β‐catenin–related pathways

et al. 2019

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“…However, low porosity of the acellular tracheal matrix might lead to incomplete cartilage regeneration [189]; therefore, they used laser micropore technology to alter scaffold porosity, with in vivo results confirming that the technique improved the cartilage matrix and the mechanical strength of the scaffolds. Furthermore, artificial biomaterial-based scaffolds seeded with MSCs, such as Col-based electrospun scaffolds [190] and core−shell nanofibrous scaffolds [191], represent viable options for replacing a damaged trachea, although scaffolds loaded with MSCs promote epithelium formation and angiogenesis in vivo but in the absence of cartilage formation [192].…”

Section: Msc-based Regenerative Medicinementioning

confidence: 99%

Mesenchymal Stem Cells for Regenerative Medicine

Han

Zhang

et al. 2019

Cells

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In recent decades, the biomedical applications of mesenchymal stem cells (MSCs) have attracted increasing attention. MSCs are easily extracted from the bone marrow, fat, and synovium, and differentiate into various cell lineages according to the requirements of specific biomedical applications. As MSCs do not express significant histocompatibility complexes and immune stimulating molecules, they are not detected by immune surveillance and do not lead to graft rejection after transplantation. These properties make them competent biomedical candidates, especially in tissue engineering. We present a brief overview of MSC extraction methods and subsequent potential for differentiation, and a comprehensive overview of their preclinical and clinical applications in regenerative medicine, and discuss future challenges.

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“…Heatmap representing the proportion of publications by year that utilized specific translational research methodologies from construct characterization to human trial to investigate laryngeal tissue engineering 85‐87,91,92,94,96,97,198‐306 …”

Section: Discussionmentioning

confidence: 99%

Tissue engineering applications in otolaryngology—The state of translation

Niermeyer

Rodman

et al. 2020

Laryngoscope Investig Oto

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While tissue engineering holds significant potential to address current limitations in reconstructive surgery of the head and neck, few constructs have made their way into routine clinical use. In this review, we aim to appraise the state of head and neck tissue engineering over the past five years, with a specific focus on otologic, nasal, craniofacial bone, and laryngotracheal applications. A comprehensive scoping search of the PubMed database was performed and over 2000 article hits were returned with 290 articles included in the final review. These publications have addressed the hallmark characteristics of tissue engineering (cellular source, scaffold, and growth signaling) for head and neck anatomical sites. While there have been promising reports of effective tissue engineered interventions in small groups of human patients, the majority of research remains constrained to in vitro and in vivo studies aimed at furthering the understanding of the biological processes involved in tissue engineering. Further, differences in functional and cosmetic properties of the ear, nose, airway, and craniofacial bone affect the emphasis of investigation at each site. While otolaryngologists currently play a role in tissue engineering translational research, continued multidisciplinary efforts will likely be required to push the state of translation towards tissue‐engineered constructs available for routine clinical use. Level of Evidence NA.

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Restoring tracheal defects in a rabbit model with tissue engineered patches based on TGF-β3-encapsulating electrospun poly(l-lactic acid-co-ε-caprolactone)/collagen scaffolds

Cited by 8 publications

References 21 publications

Kartogenin preconditioning commits mesenchymal stem cells to a precartilaginous stage with enhanced chondrogenic potential by modulating JNK and β‐catenin–related pathways

Kartogenin preconditioning commits mesenchymal stem cells to a precartilaginous stage with enhanced chondrogenic potential by modulating JNK and β‐catenin–related pathways

Mesenchymal Stem Cells for Regenerative Medicine

Tissue engineering applications in otolaryngology—The state of translation

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