Inducing Pluripotent Stem Cells via Gene Introduction
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Solution Overview
Problem
Current methods for generating human pluripotent stem cells suitable for cell replacement therapy face challenges due to low success rates and immunological rejection issues, particularly in using ES cells and iPS cells, which are not efficiently induced from human postnatal tissues.
Innovation Solution
Introduction of specific genes such as Oct3/4, Sox2, and Klf4, with or without c-Myc or histone deacetylase inhibitors, into undifferentiated stem cells from human postnatal tissues to induce ES cell-like pluripotent stem cells, which can self-renew and differentiate into various tissues, thereby avoiding immunological rejection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If nuclear transplantation is used to prepare ES cells comprising the patient's genome, then immunological rejection is avoided, but the success rate remains low and no success has been made in humans
Solution Approach 1:
The invention changes the parameters of gene introduction by selecting specific genes (Oct3/4, Sox2, Klf4, and/or c-Myc) and their combinations, along with controlling transfection efficiency and culture conditions, to transform somatic cells into pluripotent stem cells with high efficiency in humans
Solution Approach 2:
The invention extracts and utilizes the key transcription factors (Oct3/4, Sox2, Klf4, c-Myc) that control pluripotency, introducing them into somatic cells to induce pluripotent stem cell formation, thereby avoiding the need for nuclear transplantation
2Adaptability or versatility
If iPS cells are induced by introducing four genes (Oct3/4, Sox2, Klf4, c-Myc) into fibroblasts, then ES cell-like pluripotent stem cells can be obtained, but the induction rate is low and it has not been successful in humans
Solution Approach 1:
The invention optimizes parameters by selecting specific gene combinations (Oct3/4, Sox2, Klf4 with or without c-Myc), controlling transfection methods and efficiency, and adjusting culture conditions to achieve high induction rates of pluripotent stem cells from human somatic cells
Solution Approach 2:
The invention employs dynamic culture conditions including sequential media changes, passage timing optimization, and conditional gene expression control to enhance the induction efficiency and maintain pluripotency of induced cells
3Duration of action of moving object
If ES cells or EG cells are used for cell replacement therapy, then long-term self-renewal and pluripotency are achieved, but immunological rejection occurs unless the genome matches the patient
Solution Approach 1:
The invention creates a genetic copy of the patient's own genome by reprogramming their somatic cells, producing pluripotent stem cells that carry the identical genetic information and can self-renew long-term without triggering immunological rejection
Solution Approach 2:
The invention changes the cellular state from differentiated somatic cell to pluripotent stem cell through controlled introduction of reprogramming factors, maintaining the original genome while acquiring long-term self-renewal capability and pluripotency
Data Source
AI summary
Establishment of human pluripotent stem cells having properties close to human ES cells with the genome of the patient per se that can circumvent immunological rejection of transplanted cells from cells derived from a postnatal human tissue are described. Human pluripotent stem cells can be induced by introducing three genes of Oct3/4, Sox2 and Klf 4, or three genes of Oct3/4, Sox2 and Klf 4 plus the c-Myc gene or a histone deacetylase (HDAC) inhibitor of undifferentiated stem cells present in various human postnatal tissues in which each gene of Tert, Nanog, Oct3/4 and Sox2 has not undergone epigenetic inactivation.