Banas Agnieszka, Teratani Takumi, Yamamoto Yusuke, Tokuhara Makoto, Takeshita Fumitaka, Osaki Mitsuhiko, Kato Takashi, Okochi Hitoshi, Ochiya Takahiro
Section for Studies on Metastasis, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
J Gastroenterol Hepatol. 2009 Jan;24(1):70-7. doi: 10.1111/j.1440-1746.2008.05496.x. Epub 2008 Jun 25.
Multipotential mesenchymal stem cells (MSC), present in many organs and tissues, represent an attractive tool for the establishment of a successful stem cell-based therapy in the field of regeneration medicine. Adipose tissue mesenchymal stem cells (AT-MSC), known as adipose-derived stem cells (ASC) are especially attractive in the context of future clinical applications because of their high accessibility and minimal invasiveness during the procedure to obtain them. The goal of the present study was to induce human ASC into functional hepatocytes in vitro within a very short period of time and to check their therapeutic potential in vivo.
In vitro generated ASC-derived hepatocytes were checked for hepatocyte-specific markers and functions. Afterwards, they were transplanted into nude mice with liver injury. Twenty-four hours after transplantation, biochemical parameters were evaluated in blood serum.
We have shown here that ASC can be differentiated into hepatocytes within 13 days and can reach the functional properties of primary human hepatocytes. After transplantation into mice with acute liver failure, ASC-derived hepatocytes can restore such liver functions as ammonia and purine metabolism. Markers of liver injury, alanine aminotransferase, aspartate aminotransferase, as well as ammonia, were decreased after ASC-derived hepatocyte transplantation.
Our data highlight the properties of ASC as having a special affinity for hepatocyte differentiation in vitro and liver regeneration in vivo. Thus, ASC may be a superior choice for the establishment of a therapy for injured liver.
多能间充质干细胞（MSC）存在于许多器官和组织中，是再生医学领域建立成功的基于干细胞治疗的有吸引力的工具。脂肪组织间充质干细胞（AT-MSC），即脂肪来源干细胞（ASC），由于其在获取过程中具有高可及性和微创性，在未来临床应用中特别具有吸引力。本研究的目的是在极短时间内将人ASC体外诱导为功能性肝细胞，并检测其体内治疗潜力。
对体外生成的ASC来源的肝细胞进行肝细胞特异性标志物和功能检测。之后，将它们移植到肝损伤的裸鼠体内。移植后24小时，评估血清中的生化参数。
我们在此表明，ASC可在13天内分化为肝细胞，并可达到原代人肝细胞的功能特性。移植到急性肝衰竭小鼠体内后，ASC来源的肝细胞可恢复氨和嘌呤代谢等肝功能。ASC来源的肝细胞移植后，肝损伤标志物丙氨酸转氨酶、天冬氨酸转氨酶以及氨水平均降低。
我们的数据突出了ASC在体外对肝细胞分化以及体内肝再生具有特殊亲和力的特性。因此，ASC可能是建立肝损伤治疗方法的更佳选择。
