Liver Stem Cell Conditioned Medium for Regenerative Therapy
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Solution Overview
Problem
Current cell-based therapies for regenerative medicine face challenges such as immune reactions, risk of uncontrollable stem cell proliferation, and potential for tumour formation, along with limitations in treating organ injuries and liver disorders effectively.
Innovation Solution
A cell-free composition derived from adult-derived human liver stem/progenitor cells (ADHLSC) conditioned medium (ADHLSC-CM) is developed, enriched with growth factors, chemokines, and cytokines, which can be used to treat organ injuries, liver disorders, and other tissue-related issues without the risks associated with cell transplantation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If cell-based therapies using stem cells are used for regenerative medicine, then tissue regeneration and organ repair are improved, but immune reactions and risk of uncontrollable proliferation occur
Solution Approach 1:
The patent extracts the beneficial secretome components (growth factors, cytokines, chemokines) from the stem cells themselves, creating a cell-free composition. This separates the therapeutic factors that promote tissue regeneration from the cellular components that cause immune reactions and uncontrolled proliferation, thereby resolving the technical contradiction between effectiveness and safety
Solution Approach 2:
The patent creates a cell-free copy of the stem cell secretome that replicates the regenerative effects without using actual living cells. The conditioned medium contains replicated copies of the beneficial signaling molecules, providing therapeutic action without the hazards of cell transplantation such as immune rejection and tumour formation
2Reliability
If organ transplantation is performed to treat organ failure, then organ function is restored, but organ shortage and need for lifelong immunosuppression occur
Solution Approach 1:
The patent extracts the regenerative capacity from donor organs by isolating the secretome components in conditioned medium. This allows the therapeutic factors to be produced in vitro without requiring actual organ transplantation, thereby resolving the contradiction between restoring organ function and the limited availability of donor organs
Solution Approach 2:
The patent uses a disposable cell-free composition (conditioned medium) that can be produced indefinitely in bioreactors without depleting donor organ resources. This replaces the scarce, irreplaceable transplanted organ with a renewable, manufacturable therapeutic product that can be produced on demand
3Object-affected harmful factors
If MSC secretome is used as cell-free composition, then immune reactions are reduced, but composition and activity variability occur depending on cell origin and culture parameters
Solution Approach 1:
The patent systematically controls and standardizes culture parameters (cell density, passage number, culture medium composition, incubation time, temperature, CO2 levels) to ensure consistent secretome composition across different batches. By optimizing and fixing these parameters, the patent achieves reproducible composition while maintaining the immunomodulatory benefits of the MSC secretome
Solution Approach 2:
The patent develops a universal conditioned medium formulation that can be produced from different MSC sources (bone marrow, adipose tissue, umbilical cord) while maintaining consistent therapeutic activity. The standardized protocol ensures that regardless of the original cell source, the resulting secretome composition falls within a reliable therapeutic range, reducing batch-to-batch variability
Data Source
AI summary
The invention relates to cell-free compositions obtained by culturing adult-derived human liver stem/progenitor cells (ADHLSC) in cell culture medium and isolating the resulting conditioned medium (ADHLSC-CM) that has advantageous properties, such as anti-fibrotic effects. ADHLSC-CM, compositions based on ADHLSC-CM, and other related and derived products, can be used in cell culture processes or as a medicament, more particularly for the treatment of diseases involving organ injury, organ failure, in organ or cell transplantation or the pathological disruption, inflammation, degeneration, and/or proliferation of cells within a tissue or an organ, in particular within liver.