mRNA-Based Therapy for Liver Regeneration
As one of the largest and most important metabolic organs, the liver has considerable regeneration capacity. However, when chronically or severely injured, the regeneration capacity of hepatocytes times out, and finally the liver loses its ability to regenerate, leading to liver diseases, such as end-stage liver disease and cirrhosis. The limits of liver transplantation require the development of new strategies to attenuate liver disease progression and reestablish its function by promoting intrinsic regeneration. mRNA-based therapy as a safe new potential therapeutic tool induces the rapid expansion of the functional of hepatocytes and harnesses recovery of liver function, by delivering regenerative factors to injured livers in a timely, controlled fashion. Here, we give a brief introduction to mRNA-based therapeutics for liver regeneration, hoping to promote the application of such treatment to liver diseases. Creative Biogene is a leading service provider for mRNA-based drug research and development. Our extensive experience in mRNA research, an excellent team of experts, and advanced technology platforms make us an ideal partner for worldwide customers.
Key approaches used in liver regenerative medicine
For liver regenerative medicine, there are two key approaches, including cell-based therapy and tissue/organ engineering. To increase the amount of functioning tissue available and restore lost liver function, liver regenerative can be accomplished by
- Promote the survival and proliferation of mature hepatocytes.
- Regenerating new tissue to replace damaged cells.
- Create a growth-permissive environment for new cells to survive and integrate.
Cell-based therapy improves liver function by transplanting differentiated or undifferentiated cells of different origins. A deeper understanding of the cellular and molecular mechanisms associated with liver regeneration promotes the development of cell-based therapies for liver regeneration. According to the origin of liver damage, there are kinds of repair mechanisms and different used cells, involving mature hepatocytes, liver stem/progenitor cells (LSPCs), MSCs, and induced pluripotent stem cells (iPSCs). And much effort has been made for the proliferation, differentiation, and storage of these cells.
Different types of cells and their mode of application for cell‐based therapies of liver cirrhosis. (Tayyeb, A., et al., 2017)
In tissue/organ engineering, the ongoing therapeutic approaches include implantable constructs of hepatic tissues as well as whole organs. To construct hepatic tissues, natural and synthetic bioactive scaffolds are designed using nanotechnology and microchip devices. In addition, whole organ engineering has attracted attention, especially for the treatment of end-stage liver diseases. The suitable cell types, cell volume, and optimal seeding techniques still need to be discovered and further investigated.
mRNA-based therapy for liver regeneration
The temporary activation of key hepatocyte regeneration pathways is one of the methods to induce intrinsic liver regeneration. It is reported that lipid-nanoparticle-encapsulated mRNA (mRNA-LNP) is a safe, efficient, and non-integrative method to harness liver regeneration via robust and timely controlled expression of hepatocyte mitogens and regenerative factors in vivo, involving hepatocyte-growth-factor (HGF) and epidermal-growth-factor (EGF). HGF is known to have the capability to trigger a proliferative response of hepatocytes and plays an important role during liver regeneration. HGF and EGF mRNA-LNP is able to accelerate liver regeneration after non-alcoholic fatty liver disease (NAFLD) chronic injury and acetaminophen-induced liver acute injury.
Creative Biogene is offering a wide series of mRNA research services, which can accelerate the progress of mRNA-based cardiac treatment for customers worldwide. We can support our customers with the most affordable, high-quality custom mRNAs according to the desired applications. If you are interested in our services, please don't hesitate to contact us. We look forward to providing services for your next project.
- Tayyeb, A., et al. (2017). "Regenerative medicine in liver cirrhosis: promises and pitfalls." Liver Cirrhosis-Update and Current Challenges, 236-256.
- Rizvi, F., et al. (2021). "Murine liver repair via transient activation of regenerative pathways in hepatocytes using lipid nanoparticle-complexed nucleoside-modified mRNA." Nature communications, 12(1), 1-10.
- Ali, M., & Payne, S. L. (2021). "Biomaterial-based cell delivery strategies to promote liver regeneration." Biomaterials Research, 25(1), 1-21.