Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, Shriners Hospitals for Children, Boston, MA, USA; Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.
Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.
Biomaterials. 2021 Mar;270:120689. doi: 10.1016/j.biomaterials.2021.120689. Epub 2021 Jan 21.
The only treatment available for end stage liver diseases is orthotopic liver transplantation. Although there is a big donor scarcity, many donor livers are discarded as they do not qualify for transplantation. Alternatively, decellularization of discarded livers can potentially render them transplantable upon recellularization and functional testing. The success of this approach will heavily depend on the quality of decellularized scaffolds which might show variability due to factors including age. Here we assessed the age-dependent differences in liver extracellular matrix (ECM) using rat and human livers. We show that the liver matrix has higher collagen and glycosaminoglycan content and a lower growth factor content with age. Importantly, these changes lead to deterioration in primary hepatocyte function potentially due to ECM stiffening and integrin-dependent signal transduction. Overall, we show that ECM changes with age and these changes significantly affect cell function thus donor age should be considered as an important factor for bioengineering liver substitutes.
对于终末期肝病，唯一可用的治疗方法是原位肝移植。尽管供体严重短缺，但由于不符合移植条件，许多供体肝脏被丢弃。或者，通过去细胞化处理废弃的肝脏，可以在重新细胞化和功能测试后使其具有移植能力。这种方法的成功将在很大程度上取决于去细胞化支架的质量，由于包括年龄在内的各种因素，这些支架的质量可能存在差异。在这里，我们使用大鼠和人肝脏评估了年龄相关的肝细胞外基质（ECM）差异。我们发现，随着年龄的增长，肝基质中的胶原蛋白和糖胺聚糖含量更高，生长因子含量更低。重要的是，这些变化可能导致原代肝细胞功能恶化，这可能是由于 ECM 变硬和整合素依赖的信号转导。总的来说，我们发现 ECM 会随年龄而变化，这些变化会显著影响细胞功能，因此供体年龄应被视为生物工程肝脏替代物的一个重要因素。
