PITTSBURGH, Aug. 27, 2020 /PRNewswire/ -- LyGenesis, Inc., a biotechnology company focused on regenerative medicine, announced today that four peer-reviewed papers have been published on its organ regeneration technology.
LyGenesis' lead development asset is liver regeneration, which was the focus of the first two papers. Development of Ectopic Livers by Hepatocyte Transplantation into Swine Lymph Nodes by Fontes et al. was published this month in Liver Transplantation, demonstrating that functional mini-livers could be grown using the lymph node as a bioreactor. In this swine model using surgically-induced liver injuries, liver cells were isolated from the animals and then transplanted into lymph nodes in the abdominal region of the animal. In 100% of the animals the transplanted liver cells engrafted into the lymph nodes, proliferated, and formed ectopic mini-livers, which had the same structure and function as native liver tissue. The cell transplant procedure was safe, well tolerated, and as expected, the amount of liver mass generated by the ectopic livers was proportional to the degree of the native liver's damage.
The second paper, Ex Vivo Cell Therapy by Ectopic Hepatocyte Transplantation Treats Porcine Tyrosinemia Model of Acute Liver Failure by Nicolas and colleagues was published in Molecular Therapy: Methods & Clinical Developments. In this study, a human liver disease (tyrosinemia Type I) was modeled in swine, and liver cells transplanted into lymph nodes were capable of forming ectopic livers that cured all of the animals of otherwise fatal liver disease. The engraftments were again shown to be safe and also structurally and functionally similar to native liver tissue.
"The development and FDA approval of novel therapies for life-threatening diseases requires a rigorous approach to preclinical studies and our ability to grow ectopic organs to support failing organs in patients is no exception," said Dr. Paulo Fontes, LyGenesis's Chief Medical Officer and former Director of the Liver Transplant Program, Starzl Transplant Institute at the University of Pittsburgh Medical Center. "Showing that our cellular therapy was able to safely and effectively induce organogenesis – the forming of a novel, well-vascularized organ within the body – in multiple models of liver disease in large animals was a crucial step toward beginning our forthcoming clinical trial for patients with end stage liver disease who are currently ineligible for standard liver transplantation."
The other two published peer-reviewed papers focused on kidney regeneration. Kidney–in–a–Lymph Node: A Novel Organogenesis Assay to Model Human Renal Development and Test Nephron Progenitor Cell Fates published in The Journal of Tissue Engineering and Regenerative Medicine by Francipane and colleagues replicated and extended previous findings in mice showing that human ectopic kidney tissues could also be grown using the lymph node as a bioreactor. The paper also demonstrated the lymph node's remarkable ability to promote vascularization, a key rate-limiting issue for many transplant technologies, which brings blood flow and effective oxygenation to ectopic organs including kidney tissues engrafted into lymph nodes. In the paper Host Lymphotoxin-ß Receptor Signaling is Crucial for Angiogenesis of Metanephric Tissue Transplanted into Lymphoid Sites published in The American Journal of Pathology Francipane and colleagues have begun to unravel some of the molecular signaling – focusing on the lymphotoxin-ß receptor (LTßR) pathway in particular – that appears to be crucial for engrafted kidney tissue to grow and function properly.
"For a decade and supported by multiple NIH grants, my laboratory has been laying the scientific foundation for the advancement of our organ regeneration technology. Having previously published work showing that we can use the lymph node as a bioreactor to produce functioning ectopic organs including the liver, pancreas, thymus and kidney, we are now rapidly advancing those technologies, while simultaneously expanding our understanding of the molecular mechanisms that support organogenesis", said Dr. Eric Lagasse, LyGenesis's Chief Scientific Officer and Associate Professor in the Department of Pathology and also Director of the Cancer Stem Cell Center at the McGowan Institute for Regenerative Medicine at the University of Pittsburgh.
About LyGenesis, Inc.
LyGenesis is a biotechnology company whose organ regeneration technology platform enables a patient's lymph nodes to be used as bioreactors to regrow functioning ectopic organs. LyGenesis's lead allogeneic cell therapy program is focused on liver regeneration for patients with end stage liver disease. Its pipeline with positive preclinical data includes thymus, pancreas, and kidney regeneration. Privately held, LyGenesis is headquartered in Pittsburgh, Pennsylvania. To learn more, please visit lygenesis.com.
Fontes P, Komori, J, Lopez, R, Marsh, W, Lagasse, E, Development of ectopic livers by hepatocyte transplantation into swine lymph nodes. Liver Transplantation (2020).
Nicolas CT, Kaiser RA, Hickey RD, Allen KL, Du Z, VanLith CJ, Guthman RM, Amiot B, Suksanpaisan L, Han B, Francipane MG, Cheikhi A, Jiang H, Bansal A, Pandey MK, Garg I, Lowe V, Bhagwate A, O'Brien D, Kocher J-PA, DeGrado TR, Nyberg SL, Lagasse E, Lillegard JB, Ex vivo cell therapy by ectopic hepatocyte transplantation treats the porcine tyrosinemia model of acute liver failure, Molecular Therapy: Methods & Clinical Development (2020), doi: https://doi.org/10.1016/j.omtm.2020.07.009.
Francipane MG, Han B, Oxburgh L, Sims–Lucas S, Li Z, Lagasse E. Kidney–in–a–lymph node: A novel organogenesis assay to model human renal development and test nephron progenitor cell fates. J Tissue Eng Regen Med. 2019;13:1724–1731. https://doi.org/10.1002/term.2924.
Francipane, Maria Giovanna, Bing Han, Leif Oxburgh, Sunder Sims-Lucas, Zhongwei Li and Eric Lagasse. Kidney-in-a-lymph node: a novel organogenesis assay to model human renal development and test nephron progenitor cell fates. Journal of tissue engineering and regenerative medicine (2019). https://doi.org/10.1002/term.2924.
SOURCE LyGenesis, Inc.