Ex Vivo Microbiopsy Reprogramming for Scarless Tissue Regeneration
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Solution Overview
Problem
Current methods for tissue regeneration, such as skin autografts, face limitations in scalability and scarring, and there is a need for improved methods to expand tissue and prevent scarring or poor healing during wound healing processes.
Innovation Solution
The use of microbiopsies reprogrammed with induced tissue regeneration (iTR) factors, including OCT4, SOX2, KLF4, NANOG, ESRRB, NR5A2, CEBPA, MYC, LIN28A, and TERT, to revert cells to a scarless regenerative state, allowing for ex vivo expansion and transplantation without inducing pluripotency, facilitating scarless tissue regeneration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If skin autografts are used for tissue regeneration, then wound healing is achieved, but scarring occurs and tissue expansion is limited
Solution Approach 1:
The patent applies parameter changes by treating microbiopsies with iTR factors (OCT4, SOX2, KLF4, NANOG, ESRRB, NR5A2, CEBPA, MYC, LIN28A, TERT) to alter the developmental state of cells from fetal/adult to embryonic-like phenotype. This reprogramming changes the regenerative capacity parameter, enabling scarless healing that would otherwise be impossible in post-embryonic mammals
Solution Approach 2:
The patent implements preliminary action by reprogramming cells ex vivo before transplantation. The microbiopsies are treated with iTR factors in advance to induce embryonic-like regenerative properties, then transplanted to the wound site where they execute scarless regeneration without scarring
2Quantity of substance
If microbiopsies are expanded ex vivo, then tissue availability increases, but control over cell state and differentiation becomes more difficult
Solution Approach 1:
The patent uses parameter changes by defining specific culture conditions (media composition, growth factors, oxygen tension, substrate properties) that maintain cells in an embryonic-like regenerative state during ex vivo expansion. This allows tissue multiplication while preserving the desired phenotypic characteristics
Solution Approach 2:
The patent implements feedback mechanisms by monitoring cell state markers (gene expression profiles, protein markers) during ex vivo expansion and adjusting culture conditions accordingly. This ensures cells remain in the appropriate embryonic-like state while expanding tissue volume
3Reliability
If iTR factors are used to reprogram cells, then scarless regeneration is achieved, but risk of inducing pluripotency and teratoma formation increases
Solution Approach 1:
The patent applies partial action by using iTR factors transiently or at controlled levels sufficient to induce embryonic-like regenerative properties without achieving full pluripotency. This partial reprogramming achieves scarless regeneration while avoiding the teratoma risk associated with complete pluripotent reprogramming
Solution Approach 2:
The patent uses parameter changes by controlling the duration, concentration, and combination of iTR factors applied to cells. By adjusting these parameters, the treatment induces the desired regenerative phenotype without pushing cells into the pluripotent state that would lead to teratoma formation
Data Source
AI summary
Methods are provided for the ex vivo reprogramming of microbiopsies of tissue such as from the skin, wherein the cells from the tissue are reverted to a state capable of extensive expansion in volume and when transplanted in vivo, of promoting scarless tissue regeneration at the site of administration.