Feasibility, potency, and safety of growing human mesenchymal stem cells in space for clinical application

Abstract

Growing stem cells on Earth is very challenging and limited to a few population doublings. The standard two-dimensional (2D) culture environment is an unnatural condition for cell growth. Therefore, culturing stem cells aboard the International Space Station (ISS) under a microgravity environment may provide a more natural three-dimensional environment for stem cell expansion and organ development. In this study, human-derived mesenchymal stem cells (MSCs) grown in space were evaluated to determine their potential use for future clinical applications on Earth and during long-term spaceflight. MSCs were flown in Plate Habitats for transportation to the ISS. The MSCs were imaged every 24–48 h and harvested at 7 and 14 days. Conditioned media samples were frozen at −80 °C and cells were either cryopreserved in 5% dimethyl sulfoxide, RNAprotect, or paraformaldehyde. After return to Earth, MSCs were characterized to establish their identity and cell cycle status. In addition, cell proliferation, differentiation, cytokines, and growth factors’ secretion were assessed. To evaluate the risk of malignant transformation, the space-grown MSCs were subjected to chromosomal, DNA damage, and tumorigenicity assays. We found that microgravity had significant impact on the MSC capacity to secrete cytokines and growth factors. They appeared to be more potent in terms of immunosuppressive capacity compared to their identical ground control. Chromosomal, DNA damage, and tumorigenicity assays showed no evidence of malignant transformation. Therefore, it is feasible and potentially safe to grow MSCs aboard the ISS for potential future clinical applications.

Role of Apoptosis in Wound Healing and Apoptosis Alterations in Microgravity

“…These ISS-grown MSCs exhibited an MSCcharacteristic morphology and phenotype, a normal proliferative and differentiation potential. In addition, these cells were more potent in their immunosuppressive abilities compared to ground control MSCs (Huang et al, 2020). This data shows that MSCs grown in space might be useful for possible future clinical applications.…”

IL-10 mRNA Engineered MSCs Demonstrate Enhanced Anti-Inflammation in an Acute GvHD Model

“…This assay was performed using the protocols as previously described with minor modifications [27]. Briefly, MSCs were seeded into a 96-well plate with 10,000 cells/well for 1:5 cell ratio groups and 5000 cells/well for 1:10 cell ratio groups.…”

Effect of Microgravity on Endothelial Cell Function, Angiogenesis, and Vessel Remodeling During Wound Healing

“…Up-to-date techniques are needed both for the study of the mechanisms of angiogenesis alterations in space environment and for the validation of countermeasures to improve wound healing. Examples are tissue engineering, cocultures, 3D multicellular structures, lab-on-chip approaches ( Grimm et al, 2014 ; Ma et al, 2014 ; Huang et al, 2020 ), which are starting to substitute experimental animals due to ethical issues. Thorough comprehension of the molecular and biochemical mechanisms underlying cellular responses is coming from omics techniques and RNA sequence analysis of samples from simulated and real microgravity experiments ( Ma et al, 2014 ; Mao et al, 2018 ; Cui et al, 2020 ; Kasiviswanathan et al, 2020 ).…”