Immune responses to bioengineered organs

Ochando, Jordi; Charron, Dominique; Baptista, Pedro M.; Uygun, Basak E.

doi:10.1097/mot.0000000000000378

Cited by 7 publications

(8 citation statements)

References 71 publications

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“…However, a major obstacle using decellularized tissue for bioengineering applications is the limited ability to recellularize the constructs and achieve an appropriate cell density which seems to play an important role in the treatment outcome. For example, recellularized constructs seem to better stimulate tissue regeneration, recruit host cells and prevent rapid scaffold degeneration compared to scaffolds without cells, in particular for larger grafts 34 – 37 .…”

Section: Introductionmentioning

confidence: 99%

Towards a bioengineered uterus: bioactive sheep uterus scaffolds are effectively recellularized by enzymatic preconditioning

et al. 2021

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Uterine factor infertility was considered incurable until recently when we reported the first successful live birth after uterus transplantation. However, risky donor surgery and immunosuppressive therapy are factors that may be avoided with bioengineering. For example, transplanted recellularized constructs derived from decellularized tissue restored fertility in rodent models and mandate translational studies. In this study, we decellularized whole sheep uterus with three different protocols using 0.5% sodium dodecyl sulfate, 2% sodium deoxycholate (SDC) or 2% SDC, and 1% Triton X-100. Scaffolds were then assessed for bioactivity using the dorsal root ganglion and chorioallantoic membrane assays, and we found that all the uterus scaffolds exhibited growth factor activity that promoted neurogenesis and angiogenesis. Extensive recellularization optimization was conducted using multipotent sheep fetal stem cells and we report results from the following three in vitro conditions; (a) standard cell culturing conditions, (b) constructs cultured in transwells, and (c) scaffolds preconditioned with matrix metalloproteinase 2 and 9. The recellularization efficiency was improved short-term when transwells were used compared with standard culturing conditions. However, the recellularization efficiency in scaffolds preconditioned with matrix metalloproteinases was 200–300% better than the other strategies evaluated herein, independent of decellularization protocol. Hence, a major recellularization hurdle has been overcome with the improved recellularization strategies and in vitro platforms described herein. These results are an important milestone and should facilitate the production of large bioengineered grafts suitable for future in vivo applications in the sheep, which is an essential step before considering these principles in a clinical setting.

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Section: Introductionmentioning

confidence: 99%

Towards a bioengineered uterus: bioactive sheep uterus scaffolds are effectively recellularized by enzymatic preconditioning

et al. 2021

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“…Transplantation of donor tissues has been reported, but it is difficult to obtain adequate donor tissue. Even if a donor is secured and transplantation is successful, problems due to immune rejection can occur [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Motility Improvement of Biomimetic Trachea Scaffold via Hybrid 3D-Bioprinting Technology

Ahn

Son

et al. 2021

Polymers

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A trachea has a structure capable of responding to various movements such as rotation of the neck and relaxation/contraction of the conduit due to the mucous membrane and cartilage tissue. However, current reported tubular implanting structures are difficult to impelement as replacements for original trachea movements. Therefore, in this study, we developed a new trachea implant with similar anatomical structure and mechanical properties to native tissue using 3D printing technology and evaluated its performance. A 250 µm-thick layer composed of polycaprolactone (PCL) nanofibers was fabricated on a rotating beam using electrospinning technology, and a scaffold with C-shaped cartilage grooves that mimics the human airway structure was printed to enable reconstruction of cartilage outside the airway. A cartilage type scaffold had a highest rotational angle (254°) among them and it showed up to 2.8 times compared to human average neck rotation angle. The cartilage type showed a maximum elongation of 8 times higher than that of the bellows type and it showed the elongation of 3 times higher than that of cylinder type. In cartilage type scaffold, gelatin hydrogel printed on the outside of the scaffold was remain 22.2% under the condition where no hydrogel was left in other type scaffolds. In addition, after 2 days of breathing test, the amount of gelatin remaining inside the scaffold was more than twice that of other scaffolds. This novel trachea scaffold with hydrogel inside and outside of the structure was well-preserved under external flow and is expected to be advantageous for soft tissue reconstruction of the trachea.

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“…The acellular whole liver scaffold is repopulated with healthy cells to create a functional tissue that can be transplanted. One advantage of whole liver engineering approach is that the immune rejection issue can be potentially solved by engaging patient-specific liver cells such as those derived from induced pluripotent stem cells (iPSCs) in the process of recellularization 9,10 . Differentiation of iPSCs has been established for hepatocytes 11–13 and more recently for cholangiocytes 14–16 .…”

Section: Introductionmentioning

confidence: 99%

Repopulation of intrahepatic bile ducts in engineered rat liver grafts

et al. 2019

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Engineered liver grafts for transplantation with sufficient hepatic function have been developed both in small and large animal models using the whole liver engineering approach. However, repopulation of the bile ducts in the whole liver scaffolds has not been addressed yet. In this study, we show the feasibility of repopulating the bile ducts in decellularized rat livers. Biliary epithelial cells were introduced into the bile ducts of the decellularized liver scaffolds with or without hepatocytes in the parenchymal space. The recellularized grafts were cultured under perfusion for up to 2 days and histological analysis revealed that the biliary epithelial cells formed duct-like structures, with the viable hepatocyte mass residing in the parenchymal space, in an arrangement highly comparable to the native tissue. The grafts were viable and functional as confirmed by both albumin and urea assay results and the gene expression analysis of biliary epithelial cells in recellularized liver grafts. This study provides the proof-of-concept results for rat liver grafts co-populated with parenchymal and biliary epithelial cells.

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Immune responses to bioengineered organs

Cited by 7 publications

References 71 publications

Towards a bioengineered uterus: bioactive sheep uterus scaffolds are effectively recellularized by enzymatic preconditioning

Towards a bioengineered uterus: bioactive sheep uterus scaffolds are effectively recellularized by enzymatic preconditioning

Motility Improvement of Biomimetic Trachea Scaffold via Hybrid 3D-Bioprinting Technology

Repopulation of intrahepatic bile ducts in engineered rat liver grafts

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