Ezquer Fernando, Bahamonde Javiera, Huang Ya-Lin, Ezquer Marcelo
Centro de Medicina Regenerativa, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Av. Las Condes 12.438, Lo Barnechea, 7710162, Santiago, Chile.
Departamento de Fomento de la Producción Animal, Facultad de Ciencias Veterinarias y Pecuarias, Universidad de Chile, Av. Santa Rosa 11735, La Pintana, Santiago, Chile.
Stem Cell Res Ther. 2017 Jan 28;8(1):20. doi: 10.1186/s13287-016-0469-y.
The liver has the remarkable capacity to regenerate in order to compensate for lost or damaged hepatic tissue. However, pre-existing pathological abnormalities, such as hepatic steatosis (HS), inhibits the endogenous regenerative process, becoming an obstacle for liver surgery and living donor transplantation. Recent evidence indicates that multipotent mesenchymal stromal cells (MSCs) administration can improve hepatic function and increase the potential for liver regeneration in patients with liver damage. Since HS is the most common form of chronic hepatic illness, in this study we evaluated the role of MSCs in liver regeneration in an animal model of severe HS with impaired liver regeneration.
C57BL/6 mice were fed with a regular diet (normal mice) or with a high-fat diet (obese mice) to induce HS. After 30 weeks of diet exposure, 70% hepatectomy (Hpx) was performed and normal and obese mice were divided into two groups that received 5 × 10 MSCs or vehicle via the tail vein immediately after Hpx.
We confirmed a significant inhibition of hepatic regeneration when liver steatosis was present, while the hepatic regenerative response was promoted by infusion of MSCs. Specifically, MSC administration improved the hepatocyte proliferative response, PCNA-labeling index, DNA synthesis, liver function, and also reduced the number of apoptotic hepatocytes. These effects may be associated to the paracrine secretion of trophic factors by MSCs and the hepatic upregulation of key cytokines and growth factors relevant for cell proliferation, which ultimately improves the survival rate of the mice.
MSCs represent a promising therapeutic strategy to improve liver regeneration in patients with HS as well as for increasing the number of donor organs available for transplantation.
肝脏具有显著的再生能力，以补偿丢失或受损的肝组织。然而，先前存在的病理异常，如肝脂肪变性（HS），会抑制内源性再生过程，成为肝脏手术和活体供体移植的障碍。最近的证据表明，给予多能间充质基质细胞（MSCs）可以改善肝功能，并增加肝损伤患者的肝脏再生潜力。由于HS是慢性肝病最常见的形式，在本研究中，我们评估了MSCs在严重HS且肝再生受损的动物模型中的肝脏再生作用。
将C57BL/6小鼠分为两组，一组喂食常规饮食（正常小鼠），另一组喂食高脂饮食（肥胖小鼠）以诱导HS。饮食暴露30周后，进行70%肝切除术（Hpx），正常和肥胖小鼠被分为两组，在Hpx后立即通过尾静脉接受5×10个MSCs或载体。
我们证实，存在肝脂肪变性时肝再生受到显著抑制，而输注MSCs可促进肝再生反应。具体而言，给予MSCs可改善肝细胞增殖反应、PCNA标记指数、DNA合成、肝功能，并减少凋亡肝细胞数量。这些作用可能与MSCs旁分泌营养因子以及与细胞增殖相关的关键细胞因子和生长因子的肝脏上调有关，最终提高了小鼠的存活率。
MSCs是一种有前景的治疗策略，可改善HS患者的肝脏再生，并增加可用于移植的供体器官数量。
