07-05-2011, 09:35 AM
Presented by:
Susana Candia
Jahi Gist
Hashim Mehter
Priya Sateesha
Roxanne Wadia
[attachment=13370]
The BioArtificial Liver
Biology of the Liver
What does the Liver do?
Why would someone need a BioArtificial Liver?
Liver Transplantation Now
What does a BioArtificial Liver need to do?
Cellular components must be purified and every component in it must be clearly identified.
The cellular preparation must be clearly shown to not transmit any infectious diseases of any kind.
The cellular component must stay viable and active
The synthetic component must be fully biocompatible, integrity of the material and parts must also be demonstrated
The device must be able to introduce the therapeutic and regulatory molecules that a healthy liver provides, and it must also filter substances from the blood the way that the normal liver does.
Must be immunocompatible.
Blood must perfuse properly through system
Enabling Technologies
Hemodialysis/hemofiltration hollow fibers- controlled interaction of cells and circulating fluids
Maintenance and creation of a cell line
Immortalizing cells
Encapsulation-envelopment of hepatocytes in a polymeric matrix.
Microcarriers- polymeric particles containing cells
Works in Progress: Points to Consider
Bioreactor designs/Membrane configurations
Cellular vs. Acellular system
Porcine vs. Human hepatocytes
Point in Development
Liver Dialysis Unit
FDA approved in 1994
Plate dialyzer with blood on one side, dialysate is a mixture of sorbents, activated charcoal being the essential component.
For a substance to be removed, must be dialyzable and able to bind to charcoal.
“Bridge to recovery” for treat acute hepatic encephalopathy and overdoses of drugs
Post-market trials have shown the LDU to be effective in improving physiological and neurological status.
MARS®
Limited to investigational use in US.
Hollow fiber membrane hemodialyzer.
Blood on one side, human albumin on other.
Albumin recycled through circuit containing another dialyzer and carbon and anion exchanger adsorption columns.
Removes both water-soluble and protein bound substances
Keep valuable proteins
Trial have found it safe and associated with clinical improvement
ELAD®
Uses cultured human hepatocytes express normal liver-specific metabolic pathways. hollow fiber dialyzer.
Dialyzer cartridge connected to continuous hemodialysis machines, like those used for renal therapy.
Blood separated into a cellular component and a plasma component.
Plasma through dialyzer, hepatocytes on outside of hollow fibers.
Currently involved in a phase 2 clinical trial to evaluate the safety and efficiency.
BLSS
Extracorporeal hemofiltration hollow fiber membrane bioreactor with 100 grams of primary porcine hepatocytes
Whole blood is filtered
Contains blood pump, heat exchanger, oxygenator to control oxygenation and pH, and hollow fiber bioreactor
Currently undergoing phase I/II clinical trials
Patients show some improvement
HepAssist 2000 System
Four components: a hollow fiber bioreactor containing porcine hepatocytes, two charcoal filters, a membrane oxygenator, and a pump.
Must be used in conjunction with a commercially available plasma separation machine
Blood separated; plasma processed through charcoal filters to remove particulates, bacteria, then enters bioreactor
Hepatocytes must be heated and oxygenated
FDA mandated full Phase III trials
LIVERx2000
Hollow fiber cartridge
Primary porcine hepatocytes suspended in a cold collagen solution and injected inside fibers
Blood circulates outside the hollow fibers
Designed to treat both acute and chronic liver failure
Phase I/II clinical trials are underway to test the safety of efficacy of this device
Anyone treated with the LIVERx2000 will be monitored for PERV
MELS
Parallel plate design
Human hepatocytes attached to semipermeable membranes on parallel plate
Plasma separator, then plasma passes into the bioreactor
In the bioreactor, the plasma flows over the semipermeable membrane where the hepatocytes are adhered.
Current trials in Europe show promise
Demographics and Cost
Market for liver support is estimated to be substantial: $700 million in the United States and $1.4 billion worldwide.
Liver transplants have more than doubled in the past ten years, with the transplant waitlist growing in a similar fashion
Current and Future Challenges
GOAL: To produce a fully implantable bioartificial liver.
Susana Candia
Jahi Gist
Hashim Mehter
Priya Sateesha
Roxanne Wadia
[attachment=13370]
The BioArtificial Liver
Biology of the Liver
What does the Liver do?
Why would someone need a BioArtificial Liver?
Liver Transplantation Now
What does a BioArtificial Liver need to do?
Cellular components must be purified and every component in it must be clearly identified.
The cellular preparation must be clearly shown to not transmit any infectious diseases of any kind.
The cellular component must stay viable and active
The synthetic component must be fully biocompatible, integrity of the material and parts must also be demonstrated
The device must be able to introduce the therapeutic and regulatory molecules that a healthy liver provides, and it must also filter substances from the blood the way that the normal liver does.
Must be immunocompatible.
Blood must perfuse properly through system
Enabling Technologies
Hemodialysis/hemofiltration hollow fibers- controlled interaction of cells and circulating fluids
Maintenance and creation of a cell line
Immortalizing cells
Encapsulation-envelopment of hepatocytes in a polymeric matrix.
Microcarriers- polymeric particles containing cells
Works in Progress: Points to Consider
Bioreactor designs/Membrane configurations
Cellular vs. Acellular system
Porcine vs. Human hepatocytes
Point in Development
Liver Dialysis Unit
FDA approved in 1994
Plate dialyzer with blood on one side, dialysate is a mixture of sorbents, activated charcoal being the essential component.
For a substance to be removed, must be dialyzable and able to bind to charcoal.
“Bridge to recovery” for treat acute hepatic encephalopathy and overdoses of drugs
Post-market trials have shown the LDU to be effective in improving physiological and neurological status.
MARS®
Limited to investigational use in US.
Hollow fiber membrane hemodialyzer.
Blood on one side, human albumin on other.
Albumin recycled through circuit containing another dialyzer and carbon and anion exchanger adsorption columns.
Removes both water-soluble and protein bound substances
Keep valuable proteins
Trial have found it safe and associated with clinical improvement
ELAD®
Uses cultured human hepatocytes express normal liver-specific metabolic pathways. hollow fiber dialyzer.
Dialyzer cartridge connected to continuous hemodialysis machines, like those used for renal therapy.
Blood separated into a cellular component and a plasma component.
Plasma through dialyzer, hepatocytes on outside of hollow fibers.
Currently involved in a phase 2 clinical trial to evaluate the safety and efficiency.
BLSS
Extracorporeal hemofiltration hollow fiber membrane bioreactor with 100 grams of primary porcine hepatocytes
Whole blood is filtered
Contains blood pump, heat exchanger, oxygenator to control oxygenation and pH, and hollow fiber bioreactor
Currently undergoing phase I/II clinical trials
Patients show some improvement
HepAssist 2000 System
Four components: a hollow fiber bioreactor containing porcine hepatocytes, two charcoal filters, a membrane oxygenator, and a pump.
Must be used in conjunction with a commercially available plasma separation machine
Blood separated; plasma processed through charcoal filters to remove particulates, bacteria, then enters bioreactor
Hepatocytes must be heated and oxygenated
FDA mandated full Phase III trials
LIVERx2000
Hollow fiber cartridge
Primary porcine hepatocytes suspended in a cold collagen solution and injected inside fibers
Blood circulates outside the hollow fibers
Designed to treat both acute and chronic liver failure
Phase I/II clinical trials are underway to test the safety of efficacy of this device
Anyone treated with the LIVERx2000 will be monitored for PERV
MELS
Parallel plate design
Human hepatocytes attached to semipermeable membranes on parallel plate
Plasma separator, then plasma passes into the bioreactor
In the bioreactor, the plasma flows over the semipermeable membrane where the hepatocytes are adhered.
Current trials in Europe show promise
Demographics and Cost
Market for liver support is estimated to be substantial: $700 million in the United States and $1.4 billion worldwide.
Liver transplants have more than doubled in the past ten years, with the transplant waitlist growing in a similar fashion
Current and Future Challenges
GOAL: To produce a fully implantable bioartificial liver.
