Research progress in liver tissue engineering

Zhang, Lei; Zheng, Guoyan; Ye, Junsong; Yin, Yanfeng; Stoltz, Jean‐François; Isla, Natalia de

doi:10.3233/bme-171632

Cited by 11 publications

(9 citation statements)

References 26 publications

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“…Living donor programs have been successfully established, especially in children [ 26 ]. Furthermore, liver tissue engineering is another vital scientific field to hopefully address organ shortage in the near future [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Donor liver quality after hypovolemic shock and venous systemic oxygen persufflation in an experimental animal model

et al. 2018

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BackgroundThe ever growing demand for liver transplantation inevitably necessitates an expansion of the donor pool. Utilization of “shock organs” is considered suboptimal to date while the associated outcome has hardly been investigated.Materials and methodsMale Wistar rats underwent a period of 30 min of hypovolemic shock. After 24 h livers were explanted and prior to reperfusion underwent either 18 h of cold storage (CS; N = 6) or 17 h of CS followed by 60 min venous systemic oxygen persufflation (VSOP; N = 6). The outcome of “shock organs (SHBD)” was compared to heart-beating donor (HBD; N = 12) as positive control and non-heart-beating donor (NHBD; N = 12) as negative control animal groups. Liver function was assessed by measuring enzyme release (AST, ALT, LDH), bile production, portal vein pressure and hepatic oxygen uptake during reperfusion. For reperfusion, the isolated perfused rat liver system was used.ResultsLiver function was severely limited in NHBD group compared to HBD organs after 18 h of CS (e.g., AST; HBD: 32.25 ± 7.25 U/l vs. NHBD: 790 ± 414.56 U/l; p < 0.005). VSOP improved liver function of NHBD organs significantly (AST; NHBD + VSOP: 333.6 ± 149.1 U/l; p < 0.005). SHBD organs showed a comparable outcome to HBD and clearly better results than NHBD organs after 18 h of CS (AST; SHBD: 76.4 ± 21.9 U/l). After 17 h of CS accompanied by 60 min VSOP, no improvement concerning liver function and integrity of SHBD organs was observed while the results were severely deteriorated by VSOP resulting in higher enzyme release (AST; SHBD + VSOP: 213 ± 61 U/l, p < 0.001), higher portal vein pressure (SHBD: 10.8 ± 1.92 mm Hg vs. SHBD + VSOP: 21.6 ± 8.8 mm Hg; p < 0.05) and lower hepatic oxygen uptake (SHBD: 321.75 ± 3.87 ml/glw/min vs. SHBD + VSOP: 395.8 ± 46.64 ml/glw/min, p < 0.05) at 24 h.ConclusionsOur data suggest that the potential of “shock organs” within liver transplantation may be underestimated. If our findings are reproducable in humans, SHBD grafts should be considered as a valuable source for expanding the thus far limited donor pool.

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Section: Discussionmentioning

confidence: 99%

Donor liver quality after hypovolemic shock and venous systemic oxygen persufflation in an experimental animal model

et al. 2018

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“…1). Заметим, что при децеллюляризации печени рекомендуется сохранять не более 10% от количества ДНК в исходной ткани [16]. В связи с этим в протокол децеллюляризации после обработки ПАВ был введен дополнительный этап, включающий экспозицию ДФПч в растворе ДНКазы I. Как видно из рис.…”

Section: результаты и обсуждениеunclassified

Experimental approaches to creating a tissue-specific matrix for a bioartificial liver

Григорьев

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Kirillova

et al. 2020

RJTAO

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Shortage of donor organs for liver transplantation in the treatment of end-stage liver disease dictates the need to develop alternative methods that include technologies on tissue engineering and regenerative medicine. Objective: to study the ability of a tissue-specific matrix from decellularized human liver fragments (DHLF) to maintain adhesion and proliferation of human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) and HepG2 under static conditions and in a flow-through bioreactor. Materials and methods. Treatment with surfactants (SAS) – sodium dodecyl sulfate, Triton X-100 – followed by exposure to DNase was used for decellularization of human liver fragments (no more than 8 mm3). Biochemical screening included the determination of DNA quantity in the test samples. Efficiency of surfactant washing was assessed by the cytotoxicity of the matrix in the NIH 3T3 fibroblast culture. Viability and metabolic activity of cells were assessed via vital staining with a complex of fluorescent dyes LIVE/DEAD ® and PrestoBlue™ (Invitrogen, USA). Morphological examination of the liver cell-engineered constructs was carried out through histological staining and scanning electron microscopy with lanthanide contrast. Results. It was shown that the liver decellularization method used allows to obtain a biocompatible matrix with a residual DNA quantity <1%, which is capable of maintaining adhesion and proliferation of hAT-MSCs and HepG2. On day 7 of cultivation in the bioreactor, there was formation of a single conglomerate of the DHLF matrix with numerous groups of viable cells with a high nuclear-cytoplasmic ratio. The urea content in the culture medium is 1.5 ± 0.1 mmol/L, exceeding that of samples obtained under static conditions. This indicates the metabolic activity of HepG2 in the composition of the obtained culture systems. It was shown that constant flow of the culture medium in the perfusion bioreactor increased the proliferative activity of HepG2 and allowed to provide a more uniform colonization by matrix cells in comparison with static cultivation conditions. Conclusion. The conditions for uniform colonization of DHLFs in a flow-through bioreactor with cell cultures were established. The ability of the matrix to maintain adhesion and proliferation of hADSCs and HepG2 for 11 days indicates that it could be used in liver tissue engineering.

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“…tarafından fare trakeaları kullanılarak ortaya konmuştur. Bu çalışmada trakealar deterjan ile muamele edilmenin yanı sıra fiziksel muamele uy- 29 Hücre kaynağı ve karaciğere uygun metabolik aktivitenin varlığı karaciğer doku mü-hendisliği çalışmaları için ön plandadır. Bu şekilde doku mühendisliği yaklaşımı ile ortaya konan modellerin gelecekte biyoyapay karaciğerler olarak yenileyici tıp yaklaşımında yer bulması mümkün-dür.…”

Section: Solunum Si̇stemi̇ Doku Mühendi̇sli̇ği̇unclassified