The alchemists of old believed that they could find the philosophers’ stone, a substance that would not only transmute base metals into gold, but also cure all ills. Alas, the alchemists failed. But every so often, something like an alchemical transformation is achieved by today’s scientists. For example, scientists at Nanjing University and the University of Macau demonstrated, in mice, that spleens could be transformed into liver-like organs.
To accomplish this feat, the scientists didn’t require the philosophers’ stone. Instead, they used a tumor extract and autologous, allogeneic, or xenogeneic liver cells. Materials such as these will never qualify as a universal elixir. One day, however, they could be used to regenerate liver and other organs for patients who might otherwise languish at the bottom of donor organ lists. Each day, in the United States alone, 20 people die waiting for transplants.
Tissue transformation could also provide an alternative to tissue engineering (TE), which has long promised to create transplantable tissues in the laboratory. TE, which involves culturing living cells on 3D scaffolds, has had success repairing structurally simple tissues. However, it has not proven effective in regenerating large, functional organs such as the liver in clinical settings. With TE, unsatisfactory results are often due to the difficulties in assembling the blood vessel structures necessary for proper blood flow.
To address blood vessel difficulties, the Nanjing/Macau scientific team harnessed the spleen’s blood vessels. Doing so helped implanted liver cells thrive, resulting in an organ that functioned like a liver and helped the mice compensate for the liver’s surgical removal.
Additional details about the tissue transformation technique appeared June 10 in Science Advances, in an article titled, “Transforming the spleen into a liver-like organ in vivo.” According to the article’s authors, transformation is a promising technique because it exploits existing organs, which possess hard-to-replicate features such as highly organized vasculature, versatile stromal cells, sophisticated extracellular matrix structure, and well-formed communication with the host body.
“[We] injected a tumor extract into the mouse spleen to remodel its tissue structure into an immunosuppressive and proregenerative microenvironment,” the article’s authors wrote. “We implanted autologous, allogeneic, or xenogeneic liver cells (either primary or immortalized), which survived and proliferated in the remodeled spleen, without exerting adverse responses.”
To assess the function of the transformed spleens, the scientists removed 90% of the mice’s livers and evaluated whether the modified organs could take over essential liver functions, finding that the transformed spleens roughly doubled in size compared to mice without the surgery and contained liver-like microstructures including bile ducts and blood vessels. Then the scientists suppressed further growth of liver cells in the remaining liver residue and the transformed spleens, finding that mice with transplanted liver cells from other mice still survived after 48 hours, indicating that they had relied on their transformed spleens.
“[This] technology could solve the fundamental challenges in tissue engineering—which include insufficient cells, immune rejection, and lack of blood vasculature—at one time,” said Lei Dong, PhD, professor, School of Life Sciences, Nanjing University, the senior author of this work. Dong also suggested that the new approach avoided focusing too much on tissue structure, and concentrated instead on restoring the tissue function in vivo.
Chunming Wang, PhD, associate professor at the University of Macau, one of the paper’s corresponding authors, highlighted safety issues: “No adverse responses were observed for as long as eight weeks, such as immune rejection or unwanted spreading of the transplanted cells.”
The scientists noted that their liver-like organ accesses blood supply differently than does a natural liver, resulting in higher oxygen tension, or pressure from oxygen dissolved in the blood. They suggest that further research should investigate whether this higher oxygen tension could impact the liver cells over time. They also recommend that future work be performed on larger animals with comprehensive evaluations in both efficacy and safety toward its clinical application. Nonetheless, the scientists expressed confidence that their approach could overcome longstanding obstacles in regenerative medicine and, ultimately, help regenerate large organs “on demand.”