HLA-G Expressing Stem Cell Line for Immune Tolerance
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Solution Overview
Problem
Current stem cell therapeutic agents face challenges such as immune rejection, cancer cell mutation, and limited effects due to heterologous proteins and immunogenicity, hindering their commercialization and effectiveness in treating diseases like neurological and pulmonary disorders.
Innovation Solution
A novel method for preparing trophoblast and stem cells that consecutively secrete and express HLA-G proteins, creating a culture medium with immune tolerance properties, using human body-like culture conditions and co-culturing techniques to enhance the secretion and expression of HLA-G proteins, resulting in a medium rich in extracellular vesicles and proteins with antioxidant and anti-aging effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If stem cells are acquired through long-term in vitro culture, then cell therapeutic agents can be prepared for treating diseases, but there is a risk of mutation into cancer cells and tumor formation
Solution Approach 1:
The patent applies preliminary action by pre-modifying stem cells to continuously express HLA-G proteins before transplantation. This advance modification ensures immune tolerance is established beforehand, preventing immune rejection without requiring long-term culture that could lead to cancerous mutations. The cells are prepared with the desired immune tolerance property in advance, eliminating the need for prolonged in vitro maintenance.
2Ease of operation
If heterologous proteins such as FBS are used for cell storage and culture, then cell growth is supported, but immunogenicity and immune rejection occur
Solution Approach 1:
The patent applies the extraction principle by removing heterologous proteins such as FBS from the cell culture and storage system. Instead, the invention uses autologous human proteins including HLA-G proteins that are continuously expressed by the modified stem cells. This extraction of harmful heterologous components eliminates the source of immunogenicity while maintaining cell viability through human-compatible proteins.
Solution Approach 2:
The patent applies parameter changes by modifying the protein composition parameters of the culture medium. The invention transitions from using heterologous proteins (FBS) to using human-derived proteins with specific immune tolerance properties (HLA-G proteins). This parameter change in protein source and composition fundamentally alters the immunogenicity profile from harmful to beneficial.
3Adaptability or versatility
If MHC mismatches occur, then stem cells can be transplanted, but immune rejection requires short-term or long-term follow-up
Solution Approach 1:
The patent applies the intermediary principle by introducing HLA-G proteins as a mediator between the transplanted stem cells and the recipient's immune system. These proteins act as intermediaries that actively suppress immune rejection responses, allowing MHC-mismatched transplants to be accepted without prolonged immunosuppression or follow-up treatment. The HLA-G proteins bridge the incompatibility gap between donor and recipient.
Data Source
AI summary
The disclosure relates to the establishment of a cell line having immune tolerance property using an optimal temperature profiling technique under a human body-like environment, and use thereof.The stem cell line exhibits immune tolerance property as they consecutively secret and express HLA-G proteins, and the culture medium of the stem cells contains a large amount of proteins capable of recovering various physiological functions and extracellular vesicles, and thus, the novel cell line or a culture medium thereof can be effectively used in various industries such as medicines and cosmetics.