Extracellular Vesicles for Ventilator-Induced Diaphragm Dysfunction
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Solution Overview
Problem
Current treatments for ventilator-induced diaphragm dysfunction (VIDD) and critical illness myopathy (CIM) are ineffective, and there is a need for therapies that can counteract muscle wasting caused by prolonged mechanical ventilation, immobilization, and drug side effects.
Innovation Solution
Administration of extracellular vesicles (EVs) derived from bone marrow-derived mesenchymal stromal cells (BM-MSCs) to mitigate muscle damage and promote recovery in diaphragm muscle fibers and skeletal muscles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If mechanical ventilation is applied to save lives, then patient survival is improved, but ventilator-induced diaphragm dysfunction and muscle wasting occur
Solution Approach 1:
The patent applies preliminary anti-action by administering extracellular vesicles before or during mechanical ventilation to prevent the development of VIDD and muscle wasting. The EVs are given prophylactically to counteract the harmful effects before they fully manifest, thereby maintaining diaphragm function while allowing life-saving ventilation to continue.
Solution Approach 2:
The patent uses extracellular vesicles as an intermediary substance that mediates between the harmful mechanical ventilation and the diaphragm muscle. The EVs act as a protective intermediary that absorbs or mitigates the damaging effects of ventilation on muscle tissue, allowing both ventilation and muscle preservation to coexist.
2Duration of action of moving object
If prolonged mechanical ventilation is used, then life-saving respiratory support is provided, but diaphragm muscle function deteriorates
Solution Approach 1:
The patent implements preliminary action by pre-treating patients with extracellular vesicles before prolonged mechanical ventilation begins. This preparatory treatment establishes protective mechanisms in the diaphragm muscle that persist throughout the extended ventilation period, enabling long-term respiratory support without the usual functional deterioration.
Solution Approach 2:
The patent ensures continuity of useful action by providing ongoing administration of extracellular vesicles throughout the prolonged mechanical ventilation period. This continuous treatment maintains protective levels of EVs in the system, ensuring sustained diaphragm function protection throughout the extended duration of ventilation support.
3Object-affected harmful factors
If immobilization or bed rest is applied, then patient safety is improved, but muscle atrophy and wasting occur
Solution Approach 1:
The patent uses extracellular vesicles as an intermediary that counteracts the muscle-wasting effects of immobilization. The EVs mediate between the necessary immobilization for patient safety and the harmful muscle loss, providing biochemical signals that maintain muscle protein synthesis and prevent atrophy even when mechanical use is restricted.
Data Source
AI summary
This disclosure provides a secretion centric therapy to overcome muscle wasting. Provided are mesenchymal stem cell secretion-based therapies to overcome muscle wasting due to: old age; as a consequence of immobilization (e.g., mobility restricted or paralytics administered); due to use of ventilators (e.g., in an ICU or long-term immobilization); in microgravity during long space flights; or, resulting from drug side effects (e.g., the use of weight loss drugs, chemotherapies, etc.). This disclosure further provides methods and compositions for modulating, including regulating or altering, the structure and function of diaphragm muscle cells and/or diaphragm muscle fibers in particular, and skeletal muscle in general. In certain embodiments extracellular vesicles are applied to patients affected by muscle wasting.