Engineered “mini livers” could be injected as an alternative to transplantation
Engineered “mini livers” could be injected as an alternative to transplantation
工程化“迷你肝脏”可通过注射植入,有望成为器官移植的替代方案
A technology developed by Professor Sangeeta Bhatia, SM ’93, PhD ’97, and colleagues could offer new hope to the thousands of Americans with chronic liver disease who are waiting for an organ transplant or not strong enough to tolerate one. 由 Sangeeta Bhatia 教授(SM ’93, PhD ’97)及其同事开发的一项技术,为数以千计正在等待器官移植或身体状况无法承受移植手术的美国慢性肝病患者带来了新希望。
The liver is involved in regulating blood clotting, removing bacteria from the bloodstream, metabolizing drugs, and more, and many of these essential functions are performed by specialized cells called hepatocytes. 肝脏负责调节血液凝固、清除血液中的细菌、代谢药物等多种功能,而这些重要功能大多由一种被称为“肝细胞”的特殊细胞来执行。
Bhatia’s lab has been working for a decade on ways to introduce functioning hepatocytes without surgically replacing the liver itself. In the new technique, these cells are injected directly into the body along with hydrogel microspheres that help them stay together and form connections with nearby blood vessels. Bhatia 的实验室十年来一直致力于研究如何在不进行肝脏外科置换手术的情况下,引入具有功能的肝细胞。在这项新技术中,这些细胞与水凝胶微球一起被直接注射到体内,微球有助于细胞聚集在一起,并与附近的血管建立连接。
The spheres have special properties that allow them to act like a liquid when they are closely packed together, so they can be injected through a syringe and then regain their solid structure once inside the body. 这些微球具有特殊的性质,当它们紧密堆积时表现得像液体,因此可以通过注射器注入,一旦进入体内,它们便会恢复固体结构。
“These microspheres provide the hepatocytes with a niche where they can stay localized and become connected to the host circulation much faster,” says MIT postdoc Vardhman Kumar, lead author of a paper on the work. “这些微球为肝细胞提供了一个微环境,使它们能够保持在局部,并更快地与宿主的循环系统建立连接,”该研究论文的第一作者、麻省理工学院博士后 Vardhman Kumar 表示。
The researchers have shown that the cells can remain viable in the bodies of mice for at least two months, generating many of the enzymes and other proteins that the liver produces. In the study, they were injected into the fat tissue of the belly, but they could also be delivered to other sites. 研究人员已经证明,这些细胞在小鼠体内至少可以存活两个月,并能产生肝脏所需的多种酶和其他蛋白质。在研究中,这些细胞被注射到腹部脂肪组织中,但它们也可以被输送到其他部位。
“The way we see this technology is it can provide an alternative to surgery, but it can also serve as a bridge to transplantation where these grafts can provide support until a donor organ becomes available,” Kumar says. “我们认为这项技术不仅可以作为手术的替代方案,还可以作为通往器官移植的桥梁,在供体器官到位之前,这些移植物可以提供必要的支持,”Kumar 说道。
While patients would likely need to take immunosuppressive drugs, the researchers are exploring how they might get the hepatocytes to evade the immune system or use the microspheres to deliver immunosuppressants locally. 虽然患者可能仍需服用免疫抑制药物,但研究人员正在探索如何让肝细胞避开免疫系统的攻击,或者利用微球在局部输送免疫抑制剂。