Various types of cells have been developed in the laboratory, raising hopes that transplantable organs could be developed outside the body. Still, a much-desired goal—the generation of fully functional laboratory-grown organs—has yet to be achieved. Not to be discouraged, researchers set their sights on an intermediate goal. Instead of growing an entire organ outside the body, they focused on generating transplantable cells.
These cells, which started out as fibroblasts in a mouse embryo, were reprogrammed in the laboratory to become thymus cells. When these modified cells were transplanted into a mouse, they helped establish a complete, fully organized, and functional thymus.
This success—a compelling demonstration that cellular reprogramming approaches can be used to generate an entire organ—was reported August 24 in Nature Cell Biology, in an article entitled, “An organized and functional thymus generated from FOXN1-reprogrammed fibroblasts.” The article also represents progress towards an exciting application: a thymus transplant system for people with a weakened immune system.
“Enforced Foxn1 expression is sufficient to reprogram fibroblasts into functional TECs, an unrelated cell type across a germ-layer boundary,” wrote the authors. “These FOXN1-induced TECs (iTECs) supported efficient development of both CD4+ and CD8+ T cells in vitro. On transplantation, iTECs established a complete, fully organized and functional thymus, that contained all of the TEC subtypes required to support T-cell differentiation and populated the recipient immune system with T cells.”
The study is the work of researchers based at the MRC Centre for Regenerative Medicine at theUniversity of Edinburgh. They were led by Clare Blackburn, Ph.D., who asserted, “Our research represents an important step toward the goal of generating a clinically useful artificial thymus in the lab.”
Doctors have already shown that patients with thymus disorders can be treated with infusions of extra immune cells or transplantation of a thymus organ soon after birth. The problem is that both are limited by a lack of donors and problems matching tissue to the recipient.
The production of transplantable cells in the laboratory, however, could offer hope to babies born with genetic conditions that prevent the thymus from developing properly. Older people could also be helped as the thymus is the first organ to deteriorate with age.
The technique could also offer a way of making patient-matched T cells in the laboratory that could be used in cell therapies. Such treatments could benefit bone marrow transplant patients by helping speed up the rate at which they rebuild their immune system after transplant.
Lest anyone get too carried away with these possibilities, Rob Buckle, M.D., head of Regenerative Medicine at the MRC, commented, “This is an exciting study, but much more work will be needed before this process can be reproduced in a safe and tightly controlled way suitable for use in humans.”