Direct Conversion of Somatic Cells to Stratified Epithelial Tissue
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Solution Overview
Problem
Current methods for treating skin, mucosal, and corneal ulcers are inadequate, particularly for widespread or refractory cases, as they often require invasive surgical procedures and have limitations in efficiency and availability of tissue for grafting, and existing techniques for inducing pluripotent stem cells are time-consuming and risk cancerization.
Innovation Solution
Direct conversion of somatic cells, such as skin fibroblasts and adipose-derived mesenchymal cells, into cells capable of forming stratified epithelial tissue by transducing specific genes like GATA3, OVOL1, TFAP2A, GRHL2, and c-MYC, which enables the formation of stratified epithelial tissue for wound regeneration and tissue repair.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional surgical procedures such as skin grafting and flap plasty are used to treat widespread ulcers, then wound closure can be achieved, but the procedure becomes highly invasive with high risks associated with general anesthesia and surgery
Solution Approach 1:
The patent creates in vitro copies of epithelial cell sheets by culturing patient's own epithelial cells and then transplanting these cultured cell sheets to the ulcer site. This copying approach avoids the need for invasive surgical procedures while achieving wound closure, directly resolving the contradiction between effective wound closure and surgical risks
Solution Approach 2:
The patent introduces an intermediary process of in vitro cell culture as a mediator between the patient's body and the ulcer site. Instead of directly grafting skin from donor sites, the cells are first cultured in a controlled laboratory environment to form epithelial cell sheets, which then serve as the transplant material, reducing surgical invasiveness while maintaining therapeutic effectiveness
2Reliability
If epidermal cell sheets are prepared by collecting and culturing patient's skin tissues, then wound healing can be promoted, but the process takes too long and sufficient amount of cell sheets cannot be prepared within the survival window of severely burned patients
Solution Approach 1:
The patent changes the culture parameters by using optimized culture media, temperature conditions, and cell density to accelerate epithelial cell proliferation. By modifying these cultural parameters, the preparation time for sufficient cell sheets is significantly reduced, enabling treatment within the critical survival window of severely burned patients while maintaining wound healing effectiveness
Solution Approach 2:
The patent performs preliminary actions by collecting and preparing epithelial cells immediately after injury, and maintaining them in optimal culture conditions from the outset. This preliminary preparation ensures that cell proliferation begins without delay and progresses efficiently, allowing sufficient cell sheets to be prepared within the patient's survival window while ensuring effective wound healing
3Adaptability or versatility
If existing techniques for inducing pluripotent stem cells are used, then cell regeneration can be achieved, but the process is time-consuming and carries risk of cancerization
Solution Approach 1:
The patent extracts and directly cultures epithelial cells from the patient's existing tissue samples, bypassing the need to induce pluripotent stem cells and then differentiate them. This extraction approach eliminates the time-consuming induction process and avoids the cancerization risk associated with pluripotent stem cell manipulation, while still achieving cell regeneration for wound healing
Data Source
AI summary
To convert directly from a somatic cell into a cell having the ability to form stratified epithelial tissue that can act as outer skin of the body, a method for producing a cell having the ability to form stratified epithelial tissue is provided, the method including the step of introducing into a somatic cell at least one gene expressed relatively strongly in a cell having the ability to form stratified epithelial tissue.