Construction of bioengineered hepatic tissue derived from human umbilical cord mesenchymal stem cells via aggregation culture in porcine decellularized liver scaffolds.
BACKGROUND
An individualized, tissue-engineered liver suitable for transplanting into a patient with liver disease would be of great benefit to the patient and the healthcare system. The tissue-engineered liver would possess the functions of the original healthy organ. Two fields of study, (i) using decellularized tissue as cell scaffolding, and (ii) stem cell differentiation into functional cells, are coming together to make this concept feasible. The decellularized liver scaffolds (DLS) can interact with cells to promote cell differentiation and signal transduction and three-dimensional (3D) stem cell aggregations can maintain the phenotypes and improve functions of stem cells after differentiation by undergoing cell-cell contact. Although the effects of DLS and stem cell aggregation culture have been intensively studied, few observations about the interaction between the two have been achieved.


METHODS
We established a method that combines the use of decellularized liver scaffolds and aggregation culture of MSCs (3D-DLS) and explored the effects of the two on hepatic differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs) in bioengineered hepatic tissue.


RESULTS
A higher percentage of albumin-producing cells, higher levels of liver-specific transcripts, higher urea cycle-related transcripts, and lower levels of stem cell-specific transcripts were observed in the 3D-DLS group when compared to that of hUC-MSCs in monolayer culture (2D), aggregation culture (3D), monolayer on DLS culture (2D-DLS). The gene arrays also indicated that 3D-DLS induced the differentiation from the hUC-MSC phenotype to the PHH phenotype. Liver-specific proteins albumin, CK-18, and glycogen storage were highly positive in the 3D-DLS group. Albumin secretion and ammonia conversion to urea were more effective with a higher cell survival rate in the 3D-DLS group for 14 days.


CONCLUSION
This DLS and aggregation combination culture system provides a novel method to improve hepatic differentiation, maintain phenotype of hepatocyte-like cells and sustain survival for 14 days in vitro. This is a promising strategy to use to construct bioengineered hepatic tissue.
['Li|Yi|Y|', 'Wu|Qiong|Q|', 'Wang|Yujia|Y|', 'Li|Li|L|', 'Chen|Fei|F|', 'Shi|Yujun|Y|', 'Bao|Ji|J|', 'Bu|Hong|H|']
D000818:Animals D018929:Cell Culture Techniques D002454:Cell Differentiation D022781:Hepatocytes D006801:Humans D008099:Liver D008297:Male D059630:Mesenchymal Stem Cells D013552:Swine D023822:Tissue Engineering D059467:Transcriptome D014183:Transplantation, Heterologous D014470:Umbilical Cord
bioengineered hepatic tissue umbilical cord mesenchymal stem cells aggregation culture decellularized liver scaffolds hepatic differentiation