Liver Cell Transplantation via Biliary Tree Administration
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Solution Overview
Problem
Current methods face challenges in the long-term culture and large-scale expansion of primary cholangiocytes, limiting drug screening and cell-based therapy for disorders of the extrahepatic biliary epithelium, such as biliary atresia and primary sclerosing cholangitis, due to the lack of healthy donor tissue for bile duct reconstruction.
Innovation Solution
A method for administering a suspension of liver cells, preferably cholangiocytes, directly to the biliary tree, either ex vivo or in vivo, where the cells engraft into the liver, allowing for the treatment of diseased or damaged liver tissue by suspending cells in the form of organoids or clusters that correspond to the biliary tree's volume and diameter, and retaining them until engraftment is confirmed by improved liver function markers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If primary cholangiocytes are cultured in vitro, then cell expansion is achieved, but long-term culture and large-scale expansion are limited by technical challenges
Solution Approach 1:
The patent extracts the limitation of in vitro culture by transitioning to in vivo administration. Instead of attempting to overcome the technical challenges of long-term culture through laboratory methods, the invention directly administers cells to the biliary tree where they can engraft and expand within the living organism, bypassing the unreliable in vitro culture system.
Solution Approach 2:
The biliary tree serves as an intermediary pathway that enables cell delivery and engraftment. By administering cells through the biliary tree, the patent creates a functional bridge between cell source and target tissue, allowing cells to establish themselves in the liver without requiring prolonged in vitro maintenance.
2Adaptability or versatility
If healthy donor tissue is used for bile duct reconstruction, then treatment options are improved, but lack of available tissue limits therapy development
Solution Approach 1:
The patent applies self-service by utilizing the patient's own biliary tree as the delivery pathway. The biliary tree, which is already present in the patient's body, serves as the conduit for cell administration, eliminating the need for external healthy donor tissue while enabling targeted cell delivery to the site of disease.
Solution Approach 2:
Instead of discarding the biliary tree as a compromised structure in diseased patients, the patent recovers and utilizes it as the delivery pathway. The biliary tree, even in diseased states, provides a functional route for cell administration, transforming a limitation into a therapeutic advantage.
3Reliability
If cells are administered to the biliary tree, then direct engraftment is achieved, but administration technique complexity increases
Solution Approach 1:
The biliary tree serves multiple functions: it is both the site of disease and the delivery pathway for cells. This multi-functionality simplifies the administration technique by using an existing anatomical structure rather than requiring complex external delivery systems, while still achieving direct engraftment at the target site.
Data Source
AI summary
This invention relates to in vitro and in vivo methods for engrafting liver cells, such as cholangiocytes, into a liver comprising administering the liver cells to the biliary tree of the liver. The liver cells may be in the form of aggregates and may be administered in the direction of decreasing biliary duct diameter. This may be useful for example for the treatment of an individual with a diseased or damaged liver.