TABLE 1.
Summary of selected articles addressing research on cancer stem cells and stem in vitro cultured under simulated microgravity, ordered by organ/tissue
| Cell line | Organ/tissue/cell type | Space or μg‐simulating device | Findings | References |
|---|---|---|---|---|
| H460 | Non‐small cell lung cancer | RPM | Increase in apoptosis, CSCs lost their stemness features, downregulated Nanog and Oct4 genes | Pisanu et al 15 |
| HCT116 | Colorectal cancer | RCCS | CSC; CD133/CD44 dual positive cells, giant cancer cells housing complete nuclear localization of YAP | Arun et al 14 , 48 |
|
SAOS‐2, HOS, U2OS T98G, U87MG Du145, LNCap H23 Hep3b Hela Mewo, HO‐1 |
Osteosarcoma Glioblastoma Prostate cancer Lung cancer Hepatocarcinoma Cervical carcinoma Melanoma |
HFB | CD133+ cells from cancer cell lines | Kelly et al 55 |
| Rabbit MSCs | Cartilage tissue constructs | RWV | Cartilage nature confirmed by aggrecan and collagen types I and II gene expression as well as by toluidine blue and safranin‐O staining | Ohyabu et al 57 |
| Rabbit adipose‐derived stem cells and bone marrow stromal cells | Cartilage | RCCS, novel cell carrier derived from natural cartilage ECM | Improved the induction of stem cell chondro‐genesis as well as in vivo repair of cartilage lesions in a rabbit model | Yin H et al 62 , 63 |
| hMSCs | Bone marrow, osteogenic lineage | RWV | Not suitable for a potential application in cartilage repair | Mayer‐Wagner et al 66 |
| hBMSCs | Bone marrow | ISS | r‐μg stresses reverting to a quiescent state | Bradamante et al 77 |
| hADMSCs | Adipose tissue | RPM | Oxygen is a key player for cytoskeletal alterations and modulation of gene expression | Versari et al 118 |
| Rat BMSCs | Bone‐like tissue | STLV bioreactor, chitosan/hydroxyapatite, 28 days | BM‐MSCs‐C/HAp composite microbeads | Koç Demir et al 73 |
| BMSCs | Bone marrow | Clinostat | Depolymerized actin cytoskeleton inhibits osteogenic differentiation of BMSCs through impeding nuclear aggregation of TAZ | Chen et al 76 |
| CD34‐positive human cord blood stem cells (CBSC) | Vascular tubular assemblies | RWV, with or without Cytodex‐3 microcarrier beads and VEGF | Transdifferentiation into the vascular endothelial cell phenotype and assembling into 3D tissue structures | Chiu et al 80 |
| BMSCs | Endothelium‐like cells | Clinostat | Endothelial‐specific molecules (Flk‐1 and vWF) positive | Zhang et al 82 |
| EPCs | PBMNC | 3D clinostat | Most significant increase in CD34+ and double positive Dil‐Ac‐LDL‐FITC‐Ulex‐Lectin cells, both EPC markers. Enhancing the number and angiogenic potential of EPCs | Hagiwara et al 9 |
| Pluripotent stem cell‐derived cardiomyocytes | Heart | ISS | Alterations in hiPSC‐CM calcium handling showed 2635 differentially expressed genes | Wnorowski et al 12 |
| CPCs | Cardiac tissue | ISS, 2D Clinostat | Hippo signaling; upregulation of downstream genes: YAP1 and SOD2 | Camberos et al 85 |
| Adult and neonatal CPCs | Cardiac repair | ISS | Only neonatal CPCs showed an increased expression of early developmental markers and an enhanced proliferative potential | Baio et al 84 |
| IMR90 iPSCs, hESCs (H7 and H9) | Progenitor cardiac spheres | RPM | Progenitor cardiac spheres (RPM) result in efficient generation of highly enriched hPSC‐CMs. Increase in proliferation and viability of CPCs | Jha et al 89 |
| Mouse ESCs | Mouse embryo | 2D Clinostat | Deregulation of genes involved in heart development and inhibition of cardiomyocyte specific genes | Shinde et al 46 |
| PICM‐19 | Pig liver tissue | Spaceflight, STS‐126 mission | In vitro model for assessing liver function in μg. Minor differences between 1g and μg | Talbot et al 109 |
| ADSCs | Subcutaneous adipose tissue | μg bioreactor | Stemness properties, including self‐renewal and multipotency differentiation capacities, were enhanced by spheroid forma‐tion in μg. Spheroid‐derived ADSCs showed more effective potentials to rescue liver failure | Zhang et al 108 |
|
HepG2 Human biliary tree stem/progenitor cells (hBTSCs) |
Hepatocyte carcinoma | RCCS | s‐μg promotes the formation of 3D cultures and stimulates pluripotency and glycolytic metabolism in human hepatic and biliary tree stem/progenitor cells | Costantini et al 105 |
| Human epidermal stem cells (hEpSCs) | Epidermis‐like structure | RWV bioreactor, Cytodex‐3 microcarriers | hEpSCs aggregated on the microcarriers and formed multilayer 3D epidermis structures | Lei et al 94 |
| ADSCs | Adipose tissue | 2D clinostat, CTGF | Differentiation to fibroblast cells. Col1 and ColIII, MMP1, ITGB1, and FSP1 gene expression changes involved | Ebnerasuly et al 95 |
Abbreviations: 2D, two‐dimensional; 3D, three‐dimensional; AD(M)SCs, adipose tissue‐derived (mesenchymal) stem cells; BMSCs, bone marrow mesenchymal stem cells; Col1, collagen type I gene; ColIII, collagen type III gene; CPCs, cardiac progenitor cells; CTGF, connective tissue growth factor; ESCs, embryonic stem cells; EPCs, endothelial progenitor cells; FLK1, fetal liver kinase 1; FSP1, fibroblast‐specific protein 1 gene; hBTSCs, human biliary tree stem/progenitor cells; HFB, hydrodynamic focusing bioreactor; MCS, multicellular spheroids; MMP1, matrix metalloproteinase 1 gene; PBMNCs, peripheral blood mononuclear cells; RCCS, rotary cell culture system; RPM, random positioning machine; RWV, rotating wall vessel; r‐μg, real microgravity; s‐μg, simulated microgravity; SOD2, superoxide dismutase 2; STLV, slow turning lateral vessel‐type rotating bioreactor; TAZ, PDZ‐binding motif; VEGF, vascular endothelial growth factor; vWF, von Willebrand factor; YAP1, yes‐associated protein 1 gene.