" Development of Primary Cultures of Diaphragmatic Myoblasts for Basic Research Purposes "

Обзор

Neuromuscular diseases (NMDs) affecting motor neurons (MN) induce progressive muscle denervation, and become fatal when respiratory muscles e.g. the diaphragm are affected and can no longer contract. In some cases, such as Charcot's disease (Amyotrophic lateral sclerosis-ALS), there is no cure and patients die due to respiratory failure few years after diagnosis. Investigations on NMD-induced alterations of respiratory muscles in humans are limited notably by the absence of available in vitro model based on cell cultures of diaphragm-derived myoblasts. Yet, this cell tool is likely to help in developing original therapies to limit diaphragm muscle atrophy and dysfunction in NMD. To date, only cell cultures of human myoblasts obtained from limb muscles are available, making difficult to transpose results to the diaphragm. Thus, in the present project, we propose to : 1. originally develop primary cultures of myoblasts from human diaphragm, obtained from surgical resection of diaphragmatic endometriosis, 2. characterize them in terms of differentiation status (Histology, IF), metabolism (Metabolomics by NMR, cell respiration), and gene expression (RNASeq), in comparison to primary myoblasts cultures derived from the deltoid already available in the team. This project will provide an original new tool and important data on the specificity of diaphragm-derived myoblasts, compared to limb muscle-derived myoblasts with the long-term perspective of opening new therapeutical pathways for patients with severe NMDs.

Подробное описание

Neuromuscular diseases (NMDs) affecting motor neurons (MN) induce progressive muscle denervation, and become fatal when respiratory muscles e.g. the diaphragm are affected and can no longer contract. In some cases, such as Charcot's disease (Amyotrophic lateral sclerosis-ALS), there is no cure and patients die due to respiratory failure few years after diagnosis. Investigations on NMD-induced alterations of respiratory muscles in humans are limited notably by the absence of available in vitro model based on cell cultures of diaphragm-derived myoblasts. Yet, this cell tool is likely to help in developing original therapies to limit diaphragm muscle atrophy and dysfunction in NMD. To date, only cell cultures of human myoblasts obtained from limb muscles are available, making difficult to transpose results to the diaphragm.

Thus, in the present project, we propose to :

1. originally develop primary cultures of myoblasts from human diaphragm, obtained from surgical resection of diaphragmatic endometriosis, 2. characterize them in terms of differentiation status (Histology, IF), metabolism (Metabolomics by NMR, cell respiration), and gene expression (RNASeq), in comparison to primary myoblasts cultures derived from the deltoid already available in the team.

This project will provide an original new tool and important data on the specificity of diaphragm-derived myoblasts, compared to limb muscle-derived myoblasts with the long-term perspective of opening new therapeutical pathways for patients with severe NMDs.

Вмешательства

• Другое During the surgery planned as part of the routine care of the patient, a part of the tissue sample will be saved in order to carry out the analysis planned for the research.
  During the surgery planned as part of the routine care of the patient, a part of the tissue sample will be saved in order to carry out the analysis planned for the research.

Первичные конечные точки

• Molecular characteristics [Срок оценки: Inclusion]
• Cellular characteristics [Срок оценки: Inclusion]

Вторичные конечные точки (1)

• Presence of diaphragm-derived myoblasts [Срок оценки: Inclusion]

Критерии участия

Критерии включения

• Age ≥ 18 years
• diaphragmatic endometriosis requiring surgical resection of the nodules in the diaphragm.
• Collection of non-opposition

Критерии исключения

• Inability to speak and/or read French
• Patients under tutor or curatorship
• Protected adults

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Франция · 1 центр

• Department of Thoracic Surgery - Cochin Hospital — Paris

Идентификаторы

NCT: NCT07380308 · APHP250977 · 2024-A02556-41

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗