Multi-functional chamber housing a biological component

a biological component and multi-functional technology, applied in the field of extracorporeal liver perfusion, can solve the problems of limited treatment, lack of donor organs, and purely artificial systems, which cannot replace all liver functions,

Inactive Publication Date: 2016-11-03
UNIV COLLEGE OF LONDON
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0107]The chamber is preferably cylindrical and has an aspect ratio (a)=height (h) / diameter (d) of from 10:1 to 1.3:1. This is significant for two reasons:In its upright (vertical) position such an aspect ratio provides an optimum environment (mass / volume relationship characteristics) for initial cell proliferation and for use, i.e. for transfer of oxygen and nutrients to the cells and for transfer of proteins from the cells to e.g. plasma or culture medium. It also facilitates medium exchange prior to cryopreservation. (Rapid freezing / defrosting of cells.) In its horizontal position, (particularly when the aspect ratio approaches 10:1) the biological component can be “spread”, such that a larger surface area thereof can be brought into contact with the outer wall of the chamber and heat exchange elements, thus facilitating better heating / cooling (with minimal disruption to fluidisation) due to the laterally displaced position of the heat exchange elements relative to the main chamber volume.
[0110]In a further preferred embodiment the fluid transport system has a degree of compressibility, such that it can function as a “shock absorber” during cryo-preservation, thereby additionally providing a degree of protection to the encapsulated biological component.

Problems solved by technology

However, this treatment is restricted by a lack of donor organs.
Purely artificial systems, such as albumin dialysis, are however unable to replace all the liver functions including:Detoxification,Biotransformation,Synthesis, andStorage
and whilst they have proved relatively safe in clinical trials they have not given rise to a significant improvement in patient survival.
The hypothesis underlying the incorporation of liver cells is that liver function is so complex, comprising multiple synthetic, detoxification, and metabolic pathways, that crude mechanical devices will always be inadequate to replace the range of function desired; furthermore the functions critical to buying time for liver function to recover, have not been fully defined and the use of liver cells allows both defined and undefined functions to be replaced.
The applicant's approach has been to use a cell line, and has similarities with the C3A approach which has not proved effective in clinical trials.
There are also fundamental differences between the housing and initial culture of the cells prior to use.
Thus, unmodified, such cells are unlikely to be beneficial in treating the ammonia-dependent encephalopathy of liver failure.
Fat-loaded insulin resistant HepG2 cells are resistant to cytokine and pro-oxidant induced damage, but become damage susceptible after down-regulation of AMP-activated kinase.
However, the scale up of the biological component, from a laboratory scale size, involving no more than a 70 ml volume of alginate beads, provides significant challenges, some of which are addressed herein, the solutions to which may form the basis of independent claims.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Multi-functional chamber housing a biological component
  • Multi-functional chamber housing a biological component
  • Multi-functional chamber housing a biological component

Examples

Experimental program
Comparison scheme
Effect test

Embodiment Construction

[0125]The invention provides a “functionally modular” chamber in which epithelial cells, e.g. liver cells, can be housed and manipulated through various “development / life cycle” stages. Thus, for example, liver cells can serially be: •Cultured to performance competence;[0126]Cryopreserved; and[0127]Utilized

in the same chamber, by for example, changing “solutions” and altering “conditions”.

[0128]Thus, for example, a biological component, such as, alginate beads containing liver cells, may be prepared and delivered into the “functionally modular” chamber in which:[0129]Initial proliferation to optimal cell mass and performance take place;[0130]Subsequent cryopreservation can occur, and following transportation to a sick patient, and after thawing,[0131]the cells can be perfused, in-line, in the same chamber in an extracorporeal circuit attached to the patient.

[0132]Thus, whilst the chamber (section 1.0) is central to the invention a biological component (section 2.0) is also required ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
working volumeaaaaaaaaaa
pore sizesaaaaaaaaaa
volumeaaaaaaaaaa
Login to view more

Abstract

The present invention relates to the field of extracorporeal liver perfusion and, more particularly, to the design of a chamber in which a biological component can be housed to form e.g. a bio-artificial liver (BAL). It also relates to a bio-artificial liver per se, it's components and methodological steps associated with its development and use. The chamber (10) for the biological component (100) of a bio-artificial liver (200) is configured to allow: •Proliferation of the biological component, in situ; •Cryopreservation of the biological component, in situ, and •Perfusion of the biological component, in situ.

Description

CROSS-REFERENCES TO RELATED APPLICATION[0001]This application is a continuation application of U.S. patent application Ser. No. 12 / 667,323, filed on Jan. 31, 2011, which claims priority to International Patent Application PCT / GB2008 / 002227, which claims priority to European application GB 0713595.7, filed Jul. 6, 20007, each of which are hereby incorporated by reference in their entirety.TECHNICAL FIELD[0002]The present invention relates to the field of extracorporeal liver perfusion and, more particularly, to the design of a chamber in which a biological component can be housed to form e.g. a bio-artificial liver (BAL). It also relates to a bio-artificial liver per se, it's components and methodological steps associated with its development and use.BACKGROUND OF THE INVENTION[0003]Currently, the sole cure for both acute and chronic liver disease and liver failure is transplantation. However, this treatment is restricted by a lack of donor organs. In the US alone, 17,000 patients ar...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(United States)
IPC IPC(8): A01N1/02A61M1/34C12M1/02C12M3/00C12M1/12C12M1/00A61F2/02A61M1/36C12N5/071
CPCA01N1/0247A61F2/022A61M1/3489A61M1/3689C12M41/24A01N1/0257C12M21/08C12M23/06C12M29/04A61M1/3472A01N1/02C12M25/16C12N5/0671C12N2511/00C12N2533/74C12N2533/12A61M1/3496C12N5/0012C12N5/0062C12N5/0075
Inventor SELDEN, CLAREHODGSON, HUMPHREYCOWARD, SAM
Owner UNIV COLLEGE OF LONDON
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products