Role of Mesenchymal Stem Cells in Microgravity Induced Bone Loss (MABL-A)

Microgravity Associated Bone Loss-A (MABL-A) assesses the effects of microgravity on bone marrow mesenchymal stem cells (MSCs), specifically their capacity to secrete bone forming and bone dissolving cytokines (small secreted proteins that affect other cells). MSCs produce bone-forming cells and are known to play a role in making and repairing skeletal tissues. Results could provide a better understanding of the basic molecular mechanisms of bone loss caused by spaceflight and normal aging on Earth.

Experiment will launch to the International Space Station (ISS) on the NG-20 Commercial Resupply Service mission in January, 2024.

Bone loss is a major problem at Earth gravity (1 g), and it is aggravated by microgravity in space, especially during long-duration spaceflight. Exercise slows bone loss in microgravity, but even when astronauts adopt a rigorous exercise regimen, they continue to lose about 1 – 2% of their bone mass a month. While there is a vast body of knowledge on bone homeostasis under normal gravity conditions, the mechanisms of bone loss in microgravity are poorly understood and remain to be explored.

It is not yet fully determined what signals allow bone tissue to adapt to the microgravity environment as compared to an Earth environment. Conceptually, altered biomechanical stimuli in microgravity may directly affect osteoblasts, osteoclasts, and/or their precursors, while other physiological factors such as hormone levels or poor nutrition could also contribute to bone loss.

The central hypothesis of the Role of the Microgravity Associated Bone Loss (MABL-A) investigation is that microgravity alters the activity of mesenchymal stem cells (MSCs), precursors of the bone forming osteoblasts, as well as their secretion of cytokines and growth factors regulating osteogenic and osteolytic activity. Specifically, microgravity may decrease the MSC number and disrupt the secretion of trophic factors that impede bone homeostasis by reducing new bone formation, and/or increasing bone resorption.

The MABL-A study examines the impact of age and gender on bone loss by including MSCs from young and old donors. Considering the broad age range of astronauts, including these characteristics ensures that findings of this study are applicable to all astronauts regardless of age and gender. The MABL-A study is performed in the BioServe’s BioCell hardware. The BioCell culture chamber has two Fluorinated Ethylene Propylene (FEP) membranes that support cell adhesion and gas exchange, and is compatible with temperature ranges from -95˚C to +43˚C, allowing for cryogenic storage. The BioCell supports fluid injection, media exchange, fixation, and culture preservation. The fluid manipulations are performed manually by the crew. To meet NASA's safety requirements for biological containment, BioCells are housed in a Plate Habitat (PHAB) that provides secondary containment while allowing for gas exchange. To maintain cell cultures at optimal temperature and CO2, BioCell/PHAB hardware is placed in the Space Automated Bioproduct Lab (SABL) incubator aboard the ISS.

Bone loss, a significant issue of aging on Earth, is greatly aggravated by microgravity and poses a health risk for astronauts. This investigation could support development of interventions for improving adaptation and recovery of the skeletal system during spaceflight, helping to protect crew members on future long-duration missions.

This study could improve understanding of the molecular mechanisms behind age-related bone loss on Earth and support development of novel countermeasures for this symptom of aging. Results also may lead to preventions or treatments of bone loss caused by disease.