『最新研究』碳纳米管基新型水凝胶可重建健康的肝细胞
近期，新加坡国立大学（NUS）制药科学家与国立大学卫生系统（NUHS）的临床医生共同开发了一种基于碳纳米材料的水凝胶，而这种水凝胶可促使羊膜上皮细胞（一种干细胞）生长成为成熟的肝细胞。
肝脏具有许多与消化，代谢，免疫和体内营养物质储存相关的基本功能，是人体中一个高级精密的“化工厂”，在工作 的过程中不仅可以产生许多重要的蛋白质和营养物质，还可以将有毒物质分解成对我们人体无害的化学物质。
所以，毫无疑问，大部分进入人体的物质(包括药物)都是通过肝脏处理的。这也就是为什么这个器官容易处于一种有害的病理状态，而且治疗这种肝脏病例状态的方案可选择性并不多。
诸如急性肝功能衰竭和肝癌是越来越普遍的肝脏健康问题，而且目前并没有明确的治疗方案。患者除了肝脏移植外，其他的治疗选择也是很有限。而且，最关键的问题在于，就肝脏移植这个治疗方案而言，获得健康的肝脏依然是一个严峻的挑战。
来自新加坡国立大学医学部的HO Han Kiat教授和Giorgia PASTORIN教授与NUHS的DAN Yock Young教授合作开发了一种水凝胶，可以模拟健康人肝脏中的硬度水平和纳米级表面粗糙度。
HO Han Kiat教授
当羊膜上皮细胞（AEC，一种源自孕妇羊水的干细胞）种植在这种人造基质上时，它们被刺激生长发育成成熟的肝细胞。 其中，经刺激获得的这些肝细胞可以潜在地用于细胞治疗和组织工程，以帮助患有肝脏疾病的患者。
图显示羊膜干细胞在碳纳米管表面生长后具有显着的肝细胞特征。hAECs：人羊膜上皮细胞。 HLCs：肝细胞样细胞（似于肝组织中的细胞）（图片来源：新加坡国立大学）
这些研究结果是基于HO教授及其同事在之前的一项发现。他们发现，当间充质干细胞(另一种干细胞)在碳纳米管表面生长时，即使没有额外的生长因子(刺激活细胞生长的物质)，它们也能促进干细胞向肌肉细胞的转化。
所以，利用这种策略，研究团队通过将碳纳米管整合到聚丙烯酰胺凝胶中，改变了原来的碳纳米管表面。这个想法是重建一个更柔软的基质，更好地模仿健康肝脏的基质，从而影响AECs向肝细胞的转化。
HO教授表示：“这项研究取得了非常令人鼓舞的成果。 我们发现AECs具有显着的肝细胞特征，而且相应的干细胞标记物也丢失了。而且这些细胞在表达白蛋白和药物代谢能力方面表现出肝脏特异性功能。所以，我们现在的目标是扩大这些细胞的肝功能特征，并扩大这些肝细胞的生产规模，以便成为临床应用的可持续资源。”
原文链接：
https://medicalxpress.com/news/2018-09-reconstructing-healthy-liver-cells-nanomaterial-based.html
原文内容：
Reconstructing healthy liver cells using a nanomaterial-based matrix
NUS pharmaceutical scientists, together with clinicians from the National University Health System (NUHS), have developed a nanomaterial-based hydrogel that encourages amniotic epithelial cells (a type of stem cell) to grow into mature liver cells.
The liver performs many essential functions related to digestion, metabolism, immunity and storage of nutrients within the body. It is the body's "chemical factory," producing many important proteins and nutrients. It also breaks down toxic substances into harmless chemicals in the body. Not surprisingly, the majority of substances (including drugs) that enter the body are processed through the liver. This is why, a pathological condition in this organ is so deleterious and leaves very few therapeutic options. Liver diseases such as acute liver failure and liver cancer are increasingly prevalent health issues with no clear therapeutic solutions. Apart from a liver transplant, there are limited therapeutic options for the patient. However, there is a shortage of healthy livers from donors.
Prof HO Han Kiat and Prof Giorgia PASTORIN, both from the Department of Pharmacy, NUS, have collaborated with Prof DAN Yock Young from NUHS to develop a hydrogel that can mimic the stiffness level and nanoscale surface roughness found in healthy human livers. When amniotic epithelial cells (AECs, a type of stem cell derived from the amniotic fluid in pregnant women) are grown onto this artificial matrix, they are stimulated to develop into mature liver cells. These liver cells can potentially be used in cell therapy and tissue engineering to help patients with liver conditions.
These findings are built on an earlier discovery by Prof Ho and his collaborators. They had found that, when mesenchymal stem cells (another type of stem cell) are grown on a carbon nanotube-plated surface, they catalysed the transformation of stem cells into muscle cells even in the absence of additional growth factors (substances that stimulate growth in living cells). Using this strategy, the team adapted the original carbon nanotubes' surface by incorporating them into a polyacrylamide gel. The idea is to recreate a softer matrix that better mimics that of a healthy liver to influence the transformation of the AECs into liver cells.
Prof Ho said, "This effort yielded very encouraging results. We found that the AECs acquired significant liver cell characteristics with the corresponding loss of stem cell markers. These cells demonstrated liver-specific functions in terms of expressing albumin and drug metabolising capabilities. The goal now is to expand the characterisation of the liver function of these cells and to scale up production so that this can potentially be a sustainable resource for clinical applications."
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