Table 2 Influence of µG on different stem cell types

From: Cellular response in three-dimensional spheroids and tissues exposed to real and simulated microgravity: a narrative review

Tissue type

Type of µG

Positive effects

Negative effects

Cartilage

s-µG (RCCS)

Improved quality of cartilage and promoted differentiation of Indian hedgehog and Sonic hedgehog transfected mesenchymal stem cells (MSCs) into chondrocytes; inhibited hypertrophy and aging observed during chondrogenesis106.

reduced chondrogenic potential which could be partially counteracted by a low frequency electromagnetic field107.

 

s-µG (3D clinostat)

In µG the human MSCs possess strong proliferative characteristics and retain ability to differentiate. These cells transplanted in mice formed hyaline cartilage after 7d, while 1G controls showed non-cartilage tissue with fewer cells. The µG enables culture and expansion of human MSCs without culture supplements that adversely affect transplantation108.

Human MSCs showed a strong decrease in the expression of collagen type II and aggrecan108.

Bone

r- µG (Satellite bound culture system)

 

Inhibited osteogenic differentiation and promoted adipogenic differentiation of human bone marrow-derived mesenchymal stem cells, even when osteogenesis induction conditions were provided100.

 

s-µG (RWV)

Enhanced osteoblast differentiation; mineralized bone formation. bone marrow-derived stem cells showed osteoblastic potential109.

Inhibition of proliferation and differentiation found in bone marrow-derived stem cells towards osteoblasts. Increase in adipogenesis, even under osteogenic induction conditions. Selection of highly tumorigenic cells for survival. Altered actin cytoskeleton regulation and function in bone MSCs, which is depolymerized, inhibiting osteogenesis. Also, the ECM showed reduced collagen110.

 

s-µG (RCCS)

Macroscopic 3D mineralized constructs were formed with undifferentiated mESCs encapsulated in alginate hydrogels. Constructs showed morphological, phenotypical and molecular attributes of osteogenic lineage and mechanical strength and calcium/phosphate deposition111.

 

Vascular system

s-µG (3D clinostat)

Initial cultivation of endothelial progenitor cells in µG and consequent cultivation in 1G enhanced expansion rates and angiogenic potential, including vascular endothelial growth factor (VEGF) production112.

-

 

s-µG (RWV)

After four-day culture of human cord blood stem cells they formed tubular structures and expressed endothelial phenotype markers. BMSCs differentiated into endothelial like cells in 72h with formation of capillary network113.

 

Heart

r-µG (spaceflight)

Altered cardiomyocyte behavior resulting in promoted myocardial differentiation of induced pluripotent stem cells45.

-

 

s-µG (RPM)

Progenitor stem cells differentiated into viable functional cardiomyocytes with higher yield in µG, increased induction, proliferation and viability39.

 

Blood

r-µG (spaceflight)

-

Bone marrow mesenchymal and hematopoietic stem cell lineages showed decreased differentiation, fewer megakaryocytes, and more erythrocytes with elevated fucosylation. Mechanical unloading of bone in microgravity led to strong inhibition of tissue growth and regeneration mechanisms, acting at the level of early mesenchymal and hematopoietic stem cell differentiation50.

 

r-µG (spaceflight) + s-µG (RWV)

 

Microgravity decreased the proliferation of hematopoietic stem cells by blocking the cell cycle. Microgravity induced alterations in the Kit-Ras/cAMP-cAMP response element-binding protein pathway were identified101.

Skin

r-µG (parabolic flight)

murine ESCs changed 14 genes involved in skin development in alternating hypergravity and microgravity conditions, suggesting a transition to a more differentiated cell stage102.

-

 

s-µG (RWV)

human epidermal stem cells accumulated on microcarrier beads in 3D aggregates in µG to form a tissue-like epidermis structure, but not in 1G114.

 
 

s-µG (2D clinostat)

 

Fibroblastic differentiation of adipose-derived stem cells was observed in µG without a significant effect on proliferation. µG conditions altered fibroblast gene expression115.

  1. An overview of the effects of real and simulated microgravity on stem cell differentiation in different tissue types.
  2. RCCS rotary cell culture system, RWV rotary wall vessel, RPM random positioning machine.