While several groups have successfully generated organ-like tissue in vitro using stem cells, a slew of challenges have impeded efforts aimed at translating these results for potential clinical use.
The University of Pittsburgh’s Stephen Badylak, M.D., Ph.D., who was not involved in the work, says the results reported by Dr. Takebe and his colleagues represent a significant advance for the field.
“This is the first time to be able to take iPS cells, mix them with some other cells, and in combination form something that is a viable, three-dimensional construct in vivo,” Dr. Badylak tells GEN. “Most people who are working in tissue engineering and regenerative medicine, organ engineering have always felt this could happen, but no one has really shown it. …A lot of people will be citing this paper.”
Vascularization has been one major sticking point, notes Dr. Badylak, who is deputy director of Pittsburgh’s McGowan Institute for Regenerative Medicine.
“[For] all of the people working in organ engineering—whether it’s heart, lung, liver, or kidney—the rate-limiting step right now is the ability to vascularize the construct. Everybody can grow liver cells, heart cells, and kidney cells in culture, but when you take them into the body and try to say ‘OK, now go over here and do your job,’ they all die because they don’t have a vascular network,” he says. “People have been trying different approaches to engineer vascular networks into populations of parenchymal cells.”
To date, Dr. Badylak adds, “Our attempts at recreating tissue structure are really very naïve compared to what Mother Nature can do.”
Getting lab-grown tissue to recapitulate the functions of vascularized organs has also stumped many teams.
In their paper, Dr. Takebe and his colleagues present ELISA- and gene expression-based data among other functional analyses to show that these transplanted liver buds performed some human liver functions. “They [Takebe et al.] did a good job of showing that these cells did what liver cells are supposed to do,” Dr. Badylak says.