The goal of this clinical trial is to compare the quality of mesoangioblasts isolated from various patient groups suffering from muscle atrophy. This study includes cancer cachexia and muscle-impaired elderly and a control group of the same age. The quality will be defined on these following outcomes: * The number and distribution of the mesoangioblasts in a muscle biopsy to define if there are sufficient mesoangioblasts to start a culture. * The proliferation capacity to define if we can culture them the numbers required for systemic treatment. * The myogenic capacity to define if the mesoangioblasts are sufficiently capable to generate muscle fibres. Participants will: * Undergo a muscle biopsy (needle biopsy or rest material from surgery, \~50mg) * Donate blood (\~20 ml) * Fill in SARC-F questionnaire (evaluate sarcopenia score) * Fill in SQUASH questionnaire (evaluate physical activity of previous week) Researchers will compare groups (muscle-impaired elderly vs control; cancer cachexia vs control) to see if there is a difference regarding quality. These results will define the potential of autologous mesoangioblast therapy within these groups.
No effective treatment is available for the loss of muscle tissue in non-genetic muscle diseases such as (cancer) cachexia and sarcopenia. Such a treatment would improve the quality of life, therapy success, and independency of these patients. The administration of healthy autologous muscle stem cells, called mesoangioblasts, that lead to muscle regeneration and increased muscle mass and function could be a novel therapeutic strategy to achieve this. A prerequisite is that the therapeutic potential of these mesoangioblasts is sufficient. Therefore, the main aim of this study is to assess this potential for mesoangioblasts of patients with lung cancer cachexia and with sarcopenia and determine the effect the cancer or age might have on the therapeutic potential. This study is part of a larger project, called Generate Your Muscle (GYM), which aims to develop and commercially produce a stem cell therapy for recovery of muscle mass and strength in patients with genetic and non-genetic muscle disease and muscle breakdown. This will be achieved by administering large numbers of autologous mesoangioblasts (MABs) as an Advanced Therapy Medicinal Product (asCTMP) in the arteries, which will migrate to the damaged muscle, thereby restoring muscle mass and function. This strategy can only be successful for patients suffering from cachexia or sarcopenia, if these patients have enough mesoangioblasts, if these MABs can proliferate into the numbers requested for systemic treatment, if the energy capacity of the MABs is sufficient and if these mesoangioblasts still have a high myogenic potential. The aim of this study is to determine these parameters for patients with cancer cachexia or sarcopenia, as we know that they can be affected by the underlying condition. They will be compared to age-matched controls. If positive, the MABs will qualify as asCTMP for a clinical trial in a follow-up study.
Study Type
OBSERVATIONAL
Enrollment
80
In vitro analysis on isolated mesoangioblasts obtained from muscle biopsies
Number of mesoangioblasts ex vivo isolated from muscle biopsy
The number of mesoangioblasts obtained from a muscle biopsy. Once cells reached \>80% confluency in a culture dish, FACS analysis will determine the amount of mesoangioblasts obtained.
Time frame: 1 day
Proliferation capacity of mesoangioblasts in vitro
The proliferation capacity to define whether we can culture them in the numbers required for systemic treatment. Doubling time will be assessed 3 separate instances with a hemocytometer. Population doubling level = 3.32 (log viable cells at harvest - log seeded cells)
Time frame: 1 day
Myogenic capacity of mesoangioblasts in vitro
The myogenic capacity to define if the mesoangioblasts are sufficiently capable to generate muscle fibres. Myogenic capacity is calculated as the number of nuclei in MF20-positive fibers divided by total number of nuclei per field.
Time frame: 1 day
Distribution of mesoangioblasts in a muscle biopsy
The number of mesoangioblasts in a muscle biopsy. Histochemistry will reveal the location of the pericyte-like mesoangioblasts surrounding the blood vessels when stained for pericyte marker NG2 proteoglycan.
Time frame: 1 day
Homing potential of mesoangioblasts in vitro
The homing potential of the mesoangioblasts in these patients by characterizing inflammatory parameters via qPCR. Muscle damage reflected by inflammation is essential for the migration and engraftment of mesoangioblasts in the affected muscles. Differences in gene expression levels of cytokine IL6 and cytokine mediator HMGB1 in the groups MIE and Lung cancer patients vs Controls will be determined.
Time frame: 1 day
ATP production of mesoangioblasts in vitro
ATP production as a marker for metabolic health will be determined via the CellTiterGlo assay. Luminescence (Relative Light Unit) corrected for DNA content per well determines the ATP production.
Time frame: 1 day
Difference in myogenic potential of mesoangioblasts and satellite cells in vitro
Differences in myogenic potential between mesoangioblasts and satellite cells with respect due cachexia and sarcopenia. Myogenic capacity is calculated as the number of nuclei in MF20-positive fibers divided by total number of nuclei per field.
Time frame: 1 day
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