Mitochondrial Reprogramming via iPSCs for Ischemic Recovery
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Solution Overview
Problem
Ischemia can negatively alter myocardial mitochondrial structure and function, leading to decreased contractile function and survival, and existing methods may be limited by epigenetic modifications that affect the therapeutic potential of transplanted mitochondria.
Innovation Solution
The method involves harvesting somatic cells, converting them into induced pluripotent stem cells, extracting mitochondria from these cells, and transplanting them into the patient, with optional steps of culturing, differentiating, and conditioning to enhance mitochondrial numbers or activity, and potentially reprogramming mitochondria to achieve phenotypic changes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If mitochondria are transplanted directly from somatic cells, then the process is simpler and faster, but epigenetic modifications limit the therapeutic potential and functional recovery
Solution Approach 1:
The patent applies preliminary action by converting somatic cells to iPSCs before extracting mitochondria. This pre-processing step reprograms the cells to eliminate epigenetic modifications that would otherwise limit therapeutic potential, ensuring the transplanted mitochondria have enhanced functional capabilities for post-ischemic recovery
Solution Approach 2:
The patent uses iPSCs as an intermediary between somatic cells and the final mitochondrial transplant. The iPSC conversion serves as a mediating step that resets epigenetic markers, creating a intermediate state where mitochondria can be extracted with improved therapeutic properties before being transplanted to the patient
2Reliability
If somatic cells are converted to induced pluripotent stem cells, then epigenetic modifications are reset and therapeutic potential is enhanced, but the time required for cell culture and differentiation increases
Solution Approach 1:
The patent performs preliminary iPSC conversion and mitochondrial extraction before the ischemic event occurs. By advance-preparing the reprogrammed cells and extracting mitochondria while they are in the pluripotent state with optimal mitochondrial content, the treatment is ready for immediate transplantation when needed, reducing actual treatment delays
Solution Approach 2:
The patent dynamically adjusts the timing of iPSC conversion relative to the ischemic event. Cells can be converted in advance and stored, or converted closer to the event depending on the clinical scenario, allowing flexible optimization between ensuring sufficient mitochondrial reprogramming and minimizing overall treatment time
3Quantity of substance
If mitochondria are extracted from differentiated cells, then the extraction process is simpler, but the mitochondrial numbers and activity are reduced
Solution Approach 1:
The patent exploits the local quality difference between cell types by specifically using iPSCs, which naturally have higher mitochondrial content and activity compared to differentiated somatic cells. This targeted selection of cell state maximizes the quantity and quality of mitochondria extracted for transplantation
Data Source
AI summary
Embodiments herein include methods for enhancing post-ischemic functional recovery through administration of mitochondria and related devices and methods. In an embodiment, a method for enhancing post-ischemic functional recovery is included. The method can include harvesting somatic cells from a patient or a donor, converting the somatic cells into induced pluripotent stem cells, extracting mitochondria from the induced pluripotent stem cells, and transplanting the mitochondria into the patient. Other embodiments are also included herein.