Good news for organ regeneration as LyGenesis announces four peer-reviewed publications on its tech.
Four peer-reviewed papers cover LyGenesis’ work on liver and kidney regeneration on an ectopic basis. Being able to move away from long transplants lists towards purpose-grown, histocompatible organs would be great progress for Longevity. In addition, Michael Hufford, CEO of LyGenesis, gives his own personal comments on the work.
Longevity.Technology: We have covered LyGenesis, a biotech spin-out of the University of Pittsburgh and their work on organ regeneration before. However, this announcement is significant because the success of their preclinical studies firms-up the foundation for their first human clinical trial of a cell-based therapy to regenerate ectopic organs in lymph nodes.
LyGenesis raised a $3 million Series A with Juvenescence in 2018, and followed that up with $4m in debt financing from Juvenescence and Longevity Vision Fund. The company is currently closing a $25 million B-round.
Liver paper 1 demonstrated that functional mini-livers could be grown using the lymph node as a bioreactor. In pigs with surgically-induced liver injuries, liver cells were isolated from the animals and then transplanted into lymph nodes in the abdominal region. In 100% of the animals the transplanted liver cells engrafted into the lymph nodes, proliferated, and formed ectopic mini-livers that had the same structure and function as the 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.
Liver paper 2 showed that when tyrosinemia Type I, a human liver disease, was modelled in pigs, liver cells transplanted into lymph nodes were capable of forming ectopic livers that cured all the animals of otherwise-fatal disease. The engraftments were again shown to be safe and also structurally and functionally similar to native liver tissue.
“… 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 … “
“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. “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 .”
Kidney paper 1 reported the 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 vascularisation, 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.
Kidney paper 2 looked at molecular signalling, focusing on the lymphotoxin-ß receptor (LTßR) pathway in particular; this appears to be crucial for engrafted kidney tissue to grow and function properly.
Dr Eric Lagasse, LyGenesis’s Chief Scientific Officer, commented: “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 .”
“… we are focused on keeping our momentum, closing a $25M B-round of financing, launching our first clinical trial, and developing our pipeline of organs for regeneration… “
Longevity.Technology spoke to Michael Hufford about this announcement. “Twenty years in drug development drives home the Sisyphean task that is the creation and FDA approval of new medicines – push programs forward, address setbacks, stumble backwards, and never stop pushing,” he told us. “But at LyGenesis our organ regeneration technology has been an exception to that rule.
“As these four peer-reviewed papers show – the data keep pushing us forward, as time and again the lymph node has shown itself to be an ideal bioreactor for our cellular therapy to regrow functioning, and lifesaving, ectopic organs. Now we are focused on keeping our momentum, closing a $25M B-round of financing, launching our first clinical trial, and developing our pipeline of organs for regeneration, including the thymus, kidney, and pancreas.”