Muscle Stem Cell Quality in Atrophy

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.

Eligibility Criteria:
Inclusion Criteria:

Lung cancer cachexia:

* Diagnosed with NSCLC, stage III-IV
* Diagnosed with cachexia (\>5% unintentional body weight loss in past six months, \>2% body weight loss with BMI \<20, or skeletal muscle index for males \<7.26 kg/m2; females \<5.45 kg/m2)
* Age 50-60 or 60-70
* Written informed consent

Patient group: MIE

* Scheduled for total hip, knee, or back surgery
* Age 60-70 or 70-80 year
* Written informed consent

Controls

* Patients with scheduled knee-, hip-, and back surgery
* Age 50-60, 60-70, and 70-80 year
* Age and sex-matched to patient groups
* Written informed consent

Exclusion Criteria:

* No filled-in IC
* 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 of the muscle within 4 weeks of the visit unrelated to the study
* 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