McGowan Institute for Regenerative Medicine
faculty member, Eric Lagasse, PharmD, PhD, associate professor, Department of Pathology, University of Pittsburgh School of Medicine, and his colleagues have demonstrated in a preclinical model that lymph nodes can provide a suitable home for a variety of cells and tissues from other organs, suggesting a cell-based alternative to whole organ transplantation might one day be feasible. In a report recently published in Nature Biotechnology,
Dr. Lagasse and his colleagues showed in an animal model for the first time that liver cells, thymus tissue, and insulin-producing pancreatic islet cells can thrive in lymph nodes despite being displaced from their natural sites.
In many cases liver transplantation can be the only applicable therapy for cases involving hepatitis virus infection, alcoholic cirrhosis, and other diseases, noted senior investigator Dr. Lagasse. In addition, a potential therapy for diabetes is a pancreas transplant, and children with DiGeorge syndrome lack functional thymus glands to produce essential immune cells. Potentially, the findings by Dr. Lagasse and his colleagues may offer an alternative approach to treat these conditions.
“At this time the scarcity of donor organs means many people will not survive the wait for transplantation,” said Dr. Lagasse “Cell therapies are being explored, but introducing cells into tissue already ravaged by disease decreases the likelihood of successful engraftment and restoration of function.” In the study, lymph nodes which are abundant throughout the body and have a rich blood supply, served as a new home for cells from other organs in what is called an “ectopic” transplant.
They injected healthy liver cells from a genetically-identical donor animal into lymph nodes of mice at various locations. The result was an enlarged, liver-like node that functioned akin to the liver; in fact, a single hepatized lymph node rescued mice that were in danger of dying from a lethal metabolic liver disease. The photographs show a jejunal lymph node (yellow dotted oval) not transplanted (top) and just after transplantation (bottom) with primary hepatocytes. Likewise, thymus tissue transplanted into the lymph node of mice that lacked the organ generated functional immune systems, and pancreatic islet cell transplants restored normal blood sugar control in diabetic animals.
“Our goal is not necessarily to replace the entire liver, for example, but to provide sufficient cell mass to stabilize liver function and sustain the patient’s life,” Dr. Lagasse said. “That could buy time until a donor organ can be transplanted. Perhaps, in some cases, ectopic cell transplantation in the lymph node might allow the diseased organ to recover.”
Co-authors of the paper include Junji Komori, MD, PhD, Lindsey Boone, PhD, and Aaron DeWard, PhD, all of Pitt’s Department of Pathology and the McGowan Institute, and Toshitaka Hoppo, MD, PhD, now of West Penn Allegheny Health System.
The project was funded by National Institutes of Health grants P30CA047904 (through the University of Pittsburgh Cancer Institute) and R01 DK085711.
Illustration: Jejunal lymph node (LN, yellow dotted oval) not transplanted (top) and just after transplantation (bottom) with primary hepatocytes, which were mixed with 3% Evans blue dye and Matrigel before injection. Scale bars, 1 mm. – Lagasse, et al.
University of Pittsburgh Schools of the Health Sciences Media Relations News Release (09/27/12)
Bio: Dr. Eric Lagasse