Optimizing cell sourcing for clinical translation of tissue engineered ears

Morrison, Kerry A.; Cohen, Benjamin P.; Asanbe, Ope; Dong, Xue; Harper, Alice; Bonassar, Lawrence J.; Spector, Jason A.

doi:10.1088/1758-5090/9/1/015004

Cited by 19 publications

(38 citation statements)

References 48 publications

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“…Although the elastin network was not as well developed as those of the disc constructs at the 3 month time point, the appearance of early elastin fibers is a critical indicator of the auricular cartilage phenotype. The level of elastin development is also in agreement with the findings of other studies that examined full-scale engineered ear constructs with non-100% human cell sources at similar time points [ 7 , 23 ]. Most importantly, the 1:1 ear constructs featured similar biochemical and mechanical properties to native auricular cartilage.…”

Section: Discussionsupporting

confidence: 89%

“…Disc constructs containing solely human AuCs at P3 in this study formed tissue similar to native auricular cartilage, without the need of growth factor treatments during expansion or in vitro culture. However, discs containing solely human MSCs failed to generate auricular cartilage during subcutaneous implantation, further reinforcing the findings that neocartilage formation and chondrogenic differentiation of the MSCs in the co-implant constructs is directed by the inclusion of AuCs [ 23 , 24 ].…”

Section: Discussionsupporting

confidence: 54%

“…The water composition was significantly different between constructs, with MSC discs significantly less hydrated after 3 months when compared to AuC or 1:1 discs or 1:1 ears ( S2 Fig , P < 0.05). We also measured the equilibrium modulus and hydraulic permeability of the tissue in confined compression [ 23 , 32 ].…”

Section: Resultsmentioning

confidence: 99%

“…Co-culture of MSCs with articular chondrocytes [ 19 ], meniscal fibrochondrocytes [ 17 , 18 ], and nucleus pulposus cells [ 20 ] all resulted in enhancement of cartilage development. Co-culture and co-implantation of MSCs with AuCs has also been demonstrated with animal cells [ 23 , 25 ] and human-animal cell hybrids [ 21 , 22 ]. Only one previous co-implantation study combined both AuCs and stem cells of human origin, co-implanting AuCs with adipose-derived stem cells [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, little is known about the behavior of AuCs in combination with MSCs. The co-implantation of AuCs with MSCs [ 21 – 23 ] or adipose-derived stem cells [ 24 ] has generated cartilage in vivo , yet the impact of these studies is limited due to the use of non-human cells [ 21 – 23 , 25 ], a lack of markers specific to elastic cartilage [ 21 , 22 ], or the absence of mechanical evaluation [ 22 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 54%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

et al. 2018

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Current Trends and Challenges in Biofabrication Using Biomaterials and Nanomaterials: Future Perspectives for3D/4DBioprinting

Silva

2018

3D and 4D Printing in Biomedical Applications

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Platelet‐rich plasma promotes the regeneration of cartilage engineered by mesenchymal stem cells and collagen hydrogel via the TGF‐β/SMAD signaling pathway

Fang

Jin

Huang

et al. 2019

Journal Cellular Physiology

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The tissue engineering technique using mesenchymal stem cells (MSCs) and scaffolds is promising. Transforming growth factor‐β1 (TGF‐β1) is generally accepted as an chondrogenic agent, but immunorejection and unexpected side effects, such as tumorigenesis and heterogeneity, limit its clinical application. Autogenous platelet‐rich plasma (PRP), marked by low immunogenicity, easy accessibility, and low‐cost, may be favorable for cartilage regeneration. In our study, the effect of PRP on engineered cartilage constructed by MSCs and collagen hydrogel in vitro and in vivo was investigated and compared with TGF‐β1. The results showed that PRP promoted cell proliferation and gene and protein expressions of chondrogenic markers via the TGF‐β/SMAD signaling pathway. Meanwhile, it suppressed the expression of collagen type I, a marker of fibrocartilage. Furthermore, PRP accelerated cartilage regeneration on defects with engineered cartilage, advantageous over TGF‐β1, as evaluated by histological analysis and immunohistochemical staining. Our work demonstrates that autogenous PRP may substitute TGF‐β1 as a potent and reliable chondrogenic inducer for therapy of cartilage defect.

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Optimizing cell sourcing for clinical translation of tissue engineered ears

Cited by 19 publications

References 48 publications

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

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

Current Trends and Challenges in Biofabrication Using Biomaterials and Nanomaterials: Future Perspectives for3D/4DBioprinting

Platelet‐rich plasma promotes the regeneration of cartilage engineered by mesenchymal stem cells and collagen hydrogel via the TGF‐β/SMAD signaling pathway

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