The formation of human auricular cartilage from microtic tissue: An in vivo study

Ishak, Mohamad Fikeri; Goh, Bee See; Chua, Kien Hui; Abdullah, Asma bt; Saim, Lokman; Saim, Aminuddin Bin; Idrus, Ruszymah

doi:10.1016/j.ijporl.2015.06.034

Cited by 22 publications

(17 citation statements)

References 22 publications

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“…Microtia chondrocytes have been proposed as a promising cell source due to their abilities to form elastic cartilage and since they can be isolated from the patient's microtic ear without injuring healthy cartilage ( Ishak et al, 2015 , Kamil et al, 2004 , Kobayashi et al, 2011 , Nakao et al, 2017 ). In the current study, the patient’s MCs that were expanded in a condition containing bFGF demonstrated the abilities of robust proliferation, 3D cartilage generation, and stable subcutaneous cartilage formation, which confirmed their candidacy as a practical cell source to engineer auricular cartilage for clinical application.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Regeneration of Patient-specific Ear-shaped Cartilage and Its First Clinical Application for Auricular Reconstruction

et al. 2018

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Microtia is a congenital external ear malformation that can seriously influence the psychological and physiological well-being of affected children. The successful regeneration of human ear-shaped cartilage using a tissue engineering approach in a nude mouse represents a promising approach for auricular reconstruction. However, owing to technical issues in cell source, shape control, mechanical strength, biosafety, and long-term stability of the regenerated cartilage, human tissue engineered ear-shaped cartilage is yet to be applied clinically. Using expanded microtia chondrocytes, compound biodegradable scaffold, and in vitro culture technique, we engineered patient-specific ear-shaped cartilage in vitro. Moreover, the cartilage was used for auricle reconstruction of five microtia patients and achieved satisfactory aesthetical outcome with mature cartilage formation during 2.5 years follow-up in the first conducted case. Different surgical procedures were also employed to find the optimal approach for handling tissue engineered grafts. In conclusion, the results represent a significant breakthrough in clinical translation of tissue engineered human ear-shaped cartilage given the established in vitro engineering technique and suitable surgical procedure.This study was registered in Chinese Clinical Trial Registry (ChiCTR-ICN-14005469).

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Section: Discussionmentioning

confidence: 99%

In Vitro Regeneration of Patient-specific Ear-shaped Cartilage and Its First Clinical Application for Auricular Reconstruction

et al. 2018

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“…However, the translational impact of those studies was limited by the use of neonatal bovine cartilage as the cell source. The optimal clinical cell source is autologous AuCs, isolated from either the microtic cartilage remnant [ 9 , 21 , 33 ] or a non-deforming biopsy of the contralateral ear, yielding approximately 1 g of elastic cartilage [ 34 ], similar to those used in this study. Samples this size provided ~10 million cells, similar to previous findings [ 35 ], but still insufficient to populate a pediatric-sized ear requiring >200 million cells [ 5 , 11 ].…”

Section: Discussionmentioning

confidence: 99%

Tissue engineering the human auricle by auricular chondrocyte-mesenchymal stem cell co-implantation

et al. 2018

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Children suffering from microtia have few options for auricular reconstruction. Tissue engineering approaches attempt to replicate the complex anatomy and structure of the ear with autologous cartilage but have been limited by access to clinically accessible cell sources. Here we present a full-scale, patient-based human ear generated by implantation of human auricular chondrocytes and human mesenchymal stem cells in a 1:1 ratio. Additional disc construct surrogates were generated with 1:0, 1:1, and 0:1 combinations of auricular chondrocytes and mesenchymal stem cells. After 3 months in vivo, monocellular auricular chondrocyte discs and 1:1 disc and ear constructs displayed bundled collagen fibers in a perichondrial layer, rich proteoglycan deposition, and elastin fiber network formation similar to native human auricular cartilage, with the protein composition and mechanical stiffness of native tissue. Full ear constructs with a 1:1 cell combination maintained gross ear structure and developed a cartilaginous appearance following implantation. These studies demonstrate the successful engineering of a patient-specific human auricle using exclusively human cell sources without extensive in vitro tissue culture prior to implantation, a critical step towards the clinical application of tissue engineering for auricular reconstruction.

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“…The present work is distinct from its predecessor in that it provides more expansive gene expression findings to determine if microtia surgical remnants may be equivalent to normal auricular cartilage biopsies for their potential autologous auricular reconstruction through tissue engineering. While other investigations have utilized a variety of methods to examine microtia tissue as a surrogate to normal auricular cartilage [21,24,25], this study is also the first to apply microarray analysis for that intent. In addition, BMP7, a growth factor known to enhance cartilage matrix production in vitro and in vivo [35,39] was used as a supplement in these tissue-engineering experiments and analyzed for its effects on the neocartilages developed from the remnants of microtia and normal surgical tissues.…”

Section: Discussionmentioning

confidence: 99%

“…The most appropriate source of chondrocytes for tissue engineering and regeneration of the ear, its matrix, elastic and mechanical properties is auricular cartilage [20]. Microtia remnants, human auricular, pre-auricular tags and mesenchymal stem cells have also been used as cell sources for seeding ear-shaped polymeric scaffolds [21][22][23][24][25]. The use of auricular chondrocytes isolated from microtia tissue, expanded in culture and grown in the abdominal wall of patients for human autologous ear reconstruction without a scaffold has been reported [26].…”

Section: Introductionmentioning

confidence: 99%

An analytical study of neocartilage from microtia and otoplasty surgical remnants: A possible application for BMP7 in microtia development and regeneration

et al. 2020

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To investigate auricular reconstruction by tissue engineering means, this study compared cartilage regenerated from human chondrocytes obtained from either microtia or normal (conchal) tissues discarded from otoplasties. Isolated cells were expanded in vitro, seeded onto nanopolyglycolic acid (nanoPGA) sheets with or without addition of bone morphogenetic protein-7 (BMP7), and implanted in nude mice for 10 weeks. On specimen harvest, cartilage development was assessed by gross morphology, histology, and RT-qPCR and microarray analyses. Neocartilages from normal and microtia surgical tissues were found equivalent in their dimensions, qualitative degree of proteoglycan and elastic fiber staining, and quantitative gene expression levels of types II and III collagen, elastin, and SOX5. Microarray analysis, applied for the first time for normal and microtia neocartilage comparison, yielded no genes that were statistically significantly different in expression between these two sample groups. These results support use of microtia tissue as a cell source for normal auricular reconstruction. Comparison of normal and microtia cells, each seeded on nanoPGA and supplemented with BMP7 in a slow-release hydrogel, showed statistically significant differences in certain genes identified by microarray analysis. Such differences were also noted in several analyses comparing counterpart seeded cells without BMP7. Summary data suggest a possible application for BMP7 in microtia cartilage regeneration and encourage further studies to elucidate whether such genotypic differences translate to phenotypic characteristics of the human microtic ear. The present work advances understanding relevant to the potential clinical use of microtia surgical remnants as a suitable cell source for tissue engineering of the pinna.

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The formation of human auricular cartilage from microtic tissue: An in vivo study

Cited by 22 publications

References 22 publications

In Vitro Regeneration of Patient-specific Ear-shaped Cartilage and Its First Clinical Application for Auricular Reconstruction

In Vitro Regeneration of Patient-specific Ear-shaped Cartilage and Its First Clinical Application for Auricular Reconstruction

Tissue engineering the human auricle by auricular chondrocyte-mesenchymal stem cell co-implantation

An analytical study of neocartilage from microtia and otoplasty surgical remnants: A possible application for BMP7 in microtia development and regeneration

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