The study aims to isolate and culture mesoangioblasts from muscle biopsies of two patient groups suffering from skeletal muscle atrophy to assess their potential for autologous muscle stem cell therapy. To relate this potential to the underlying…
ID
Source
Brief title
Condition
- Other condition
- Muscle disorders
Synonym
Health condition
cachexie
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
• Immunophenotype characterization of mesoangioblasts (i.e. number of the
correct cells isolated from a muscle biopsy) by Alkaline phosphatase staining
to determine stemness (>50%); and cell sorting via magnetic-activated cell
sorting (MACS) and/or fluorescent-activated cell sorting (FACS) depending on
surface antigens (>50%) • Proliferation rate of mesoangioblasts in vitro
(population doubling level: >2 every 3-4 days) • Muscle regenerative capacity
of mesoangioblasts in terms of the formation of multinucleated mature myotubes
(>25% of total nuclei).
Secondary outcome
- The metabolic health of the mesoangioblasts, based on mitochondrial
parameters (mitochondrial activity, mitochondrial DNA copy number, ATP
production). This should not be below 50%, compared to age-matched controls.
- The homing potential of the mesoangioblasts in these patients by
characterizing inflammatory parameters. Muscle damage reflected by inflammation
is essential for the migration and engraftment of mesoangioblasts in the
affected muscles. (Inflammation) markers are determined in blood via an ELISA
assay (descriptive).
- Identify a potential difference between mesoangioblasts and satellite cells
as a response to cachexia and sarcopenia.
o Number of satellite cells present in muscle tissue via (immuno)histochemistry
(descriptive)
o Muscle regenerative capacity of satellite cells in terms of the formation of
multinucleated mature myotubes (descriptive).
o Proliferation rate of satellite cells in vitro (descriptive)
Background summary
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. Myogenic stem cells have the potential to regenerate
skeletal muscle.
Study objective
The study aims to isolate and culture mesoangioblasts from muscle biopsies of
two patient groups suffering from skeletal muscle atrophy to assess their
potential for autologous muscle stem cell therapy. To relate this potential to
the underlying condition, we will collect information of the patients by
questionnaires, muscle strength measurements and blood parameters.
Study design
A mono-center observation study.
Study burden and risks
Muscle biopsies will be collected using the a thin-needle biopsy instrument,
which is a fast and routinely used procedure in diagnostic centers to harvest a
small (~30 mg) muscle fragment with the patient burden being limited to the
time of the procedure (anecdotes multiple patients). Muscle biopsies can be
painful in some cases and infections and bleeding afterward are possible, but
rare. Blood will be collected (20cc), according to standard hospital
procedures, having a low burden/risk for the participants.
P. Debyelaan 25
Maastricht 6229HX
NL
P. Debyelaan 25
Maastricht 6229HX
NL
Listed location countries
Age
Inclusion criteria
Patient group: cachexia - Diagnosed with non-small cell lung cancer (NSCLC),
stage 3-4 - Diagnosed with cachexia (>5% unintentional body weight loss in past
six months) - Age 50-60 and 60-70 - Written informed consent Patient group:
muscle impaired elderly - Scheduled for knee-, back- or hip surgery - Age 60-70
and 70-80y - Written informed consent Controls - Scheduled for knee-, back- or
hip surgery - Age 50-60, 60-70 and 70-80 - Written informed consent
Exclusion criteria
- No informed consent
- Suffering from a muscular dystrophy or other disease known to affect muscle
morphology or function
- Have a weekly alcohol intake of >= 35 units (men) or >= 24 units (women)
- Ongoing participation in other intervention clinical trials
- Major surgery within 4 weeks of the visit
- Patients unable and/or unwilling to comply with treatment and study
instructions
- Any other factor that in the opinion of the investigator excludes the patient
from the study
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL81090.068.22 |