iPSC-Derived Hepatocyte Based Bioartificial Liver Device

Tech ID: aru000827

 

Introduction

Decompensated liver disorders require liver transplantation. However, the donor organ shortage is a limiting factor. Harnessing the power of human induced pluripotent stem cell (iPSC) technology in combination with hollow fiber-based bioartificial liver (BAL) device can be beneficial to patients with liver failure. The invention aims to develop a BAL module comprised of iPSC-derived hepatocytes (iHeps) arrayed on the extracapillary space (ECS) of hollow fiber membranous capillaries that allow the flow of blood through the intracapillary space (ICS), thus mimicking the tissue microarchitecture.

 

Technology Description

For the proof-of-concept in vitro study, a cartridge having semipermeable polysulfone membrane fibers was used as an artificial liver device. As a source for human liver cells, we derived metabolically active hepatocytes from iPSCs. The iHeps on microcarrier beads were loaded into the ECS of a hollow fiber bioreactor cartridge and cultured using a closed-circuit continuous flow system. The iHeps secreted human albumin, prothrombin, and apolipoprotein B into the hollow fiber ICS media, and the continuous flow system also improved maturation of iHeps. In conclusion, the iPSC-hepatocytes in the bioartificial liver device maintained the secretory function and exhibited cell maturation. The iPSC-hepatocyte BAL has the potential to be further developed as a liver support device for the treatment of decompensated liver diseases.

 

The proof-of-concept preclinical in vitro study on the development of a prototype iPSC-hepatocyte-based bioartificial liver module has been successfully completed. The inventors are now conducting animal studies to further advance the technology.

 

 

Advantages/Novelty

• To date, non-biological liver support systems have been shown to be less effective and, while intuitively more promising, no truly effective biological device has yet been developed for human treatment purposes.

• Alternative approaches to liver organ transplantation such as non-biological and biological liver support systems have been attempted. Non-biological systems include blood transfusion, plasma exchange, hemodialysis (to remove <15 kDa factors), hemofiltration, and hemoadsorption using non-biologic adsorbents (charcoal or resin). A biological liver support system is comprised of ex vivo liver perfusion (livers from human, non-human primate and pig species) and a hepatocyte system (human or pig hepatocytes loaded onto bioreactor devices). The extracorporeal liver assist device (ELAD), HepatAssist liver support system, Molecular Adsorbent Recirculating System (MARS) and The Prometheus device have been in clinical evaluation.

 

Applications

•       The technology can be further developed into a liver support device for the treatment of decompensated liver diseases. The cell source, induced pluripotent stem cell, comes from the patient’s own cells (autologous), therefore eliminating unnecessary immune responses in liver transplant.

•       The iPSC-hep BAL can also be used in allogeneic set up (patients with different immuno-genetic background), as the membrane hollow fibers are non-permeable for cells.

 

Intellectual Property

US provisional patent filed.

 

Publications

• Ren S et al. Bioartificial Liver Device Based on Induced Pluripotent Stem Cell-Derived Hepatocytes. J Stem Cell Res Ther.2015, 5: 263. [LINK]

 

Patent Information:
Category(s):
Device(s)
For Information, Contact:
Wenyue Du
Associate - IP Management & Licensing
310-423-2241
wenyue.du@cshs.org
Inventors:
Vaithilingaraja Arumugaswami
Clive Svendsen
Keywords:
Stem Cells
xRegenerative Medicine