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Decellularized spleen matrix for reengineering functional hepatic-like tissue based on bone marrow mesenchymal stem cells.
Organogenesis ( IF 2.3 ) Pub Date : 2016-05-25 , DOI: 10.1080/15476278.2016.1185584
Junxi Xiang 1, 2 , Xinglong Zheng 1, 2 , Peng Liu 1, 2 , Lifei Yang 2 , Dinghui Dong 1, 2 , Wanquan Wu 1, 2 , Xuemin Liu 1, 2 , Jianhui Li 2, 3 , Yi Lv 1, 2
Affiliation  

Background and Aims: Decellularized liver matrix (DLM) hold great potential for reconstructing functional hepatic-like tissue (HLT) based on reseeding of hepatocytes or stem cells, but the shortage of liver donors is still an obstacle for potential application. Therefore, an appropriate alternative scaffold is needed to expand the donor pool. In this study, we explored the effectiveness of decellularized spleen matrix (DSM) for culturing of bone marrow mesenchymal stem cells (BMSCs), and promoting differentiation into hepatic-like cells.

Methods: Rats' spleen were harvested for DSM preparation by freezing/thawing and perfusion procedure. Then the mesenchymal stem cells derived from rat bone marrow were reseeded into DSM for dynamic culture and hepatic differentiation by a defined induction protocol.

Results: The research found that DSM preserved a 3-dimensional porous architecture, with native extracellular matrix and vascular network which was similar to DLM. The reseeded BMSCs in DSM differentiated into functional hepatocyte-like cells, evidenced by cytomorphology change, expression of hepatic-associated genes and protein markers, glycogen storage, and indocyanine green uptake. The albumin production (2.74±0.42 vs. 2.07±0.28 pg/cell/day) and urea concentration (75.92±15.64 vs. 52.07±11.46 pg/cell/day) in DSM group were remarkably higher than tissue culture flasks (TCF) group over the same differentiation period, P< 0.05.

Conclusion: This present study demonstrated that DSM might have considerable potential in fabricating hepatic-like tissue, particularly because it can facilitate hepatic differentiation of BMSCs which exhibited higher level and more stable functions.



中文翻译:

去细胞脾脏基质,用于基于骨髓间充质干细胞的功能性肝样组织再造。

背景与目的:去细胞肝基质(DLM)具有基于肝细胞或干细胞再播种重建功能性肝样组织(HLT)的巨大潜力,但是肝供体的短缺仍然是潜在应用的障碍。因此,需要适当的替代支架来扩大供体库。在这项研究中,我们探讨了脱细胞脾基质(DSM)在培养骨髓间充质干细胞(BMSCs)和促进分化为肝样细胞方面的有效性。

方法:通过冷冻/解冻和灌注程序收集大鼠的脾脏以制备帝斯曼。然后,通过定义的诱导方案,将源自大鼠骨髓的间充质干细胞重新接种到DSM中,以进行动态培养和肝分化。

结果:研究发现DSM保留了3维多孔结构,具有天然细胞外基质和类似于DLM的血管网络。DSM中重新播种的BMSCs分化为功能性肝细胞样细胞,其表现为细胞形态学变化,肝相关基因和蛋白质标记物的表达,糖原存储和吲哚花青绿的吸收。DSM组的白蛋白产量(2.74±0.42 vs. 2.07±0.28 pg /细胞/天)和尿素浓度(75.92±15.64 vs. 52.07±11.46 pg /细胞/天)显着高于组织培养瓶(TCF)组在相同分化时期,P <0.05。

结论:本研究表明DSM在制造肝样组织中可能具有相当大的潜力,特别是因为它可以促进具有更高水平和更稳定功能的BMSCs的肝分化。

更新日期:2016-05-25
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