# The effects of microgravity on differentiation and cell growth in stem cells and cancer stem cells

**Authors:** Daniela Grimm, Markus Wehland, Thomas J. Corydon, Peter Richter, Binod Prasad, Johann Bauer, Marcel Egli, Sascha Kopp, Michael Lebert, Marcus Krüger

PMC · DOI: 10.1002/sctm.20-0084 · Stem Cells Translational Medicine · 2020-04-30

## TL;DR

This review explores how microgravity affects stem cell and cancer stem cell behavior, with implications for space travel and medical research.

## Contribution

The paper provides a comprehensive review of microgravity's impact on stem and cancer stem cells, focusing on real and simulated conditions.

## Key findings

- Microgravity alters stem cell differentiation and growth, influencing tissue engineering.
- Cancer stem cells in gastrointestinal, lung, and osteosarcoma cancers are affected by microgravity.
- Microgravity is a new tool for studying organoid and tissue development in regenerative medicine.

## Abstract

A spaceflight has enormous influence on the health of space voyagers due to the combined effects of microgravity and cosmic radiation. Known effects of microgravity (μg) on cells are changes in differentiation and growth. Considering the commercialization of spaceflight, future space exploration, and long‐term manned flights, research focusing on differentiation and growth of stem cells and cancer cells exposed to real (r‐) and simulated (s‐) μg is of high interest for regenerative medicine and cancer research. In this review, we focus on platforms to study r‐ and s‐μg as well as the impact of μg on cancer stem cells in the field of gastrointestinal cancer, lung cancer, and osteosarcoma. Moreover, we review the current knowledge of different types of stem cells exposed to μg conditions with regard to differentiation and engineering of cartilage, bone, vasculature, heart, skin, and liver constructs.

Stem cells exposed to real or simulated microgravity show changes in growth and differentiation. The application of microgravity in cell biology represents a new technology used in the field of cancer research and translational regenerative medicine. It extends the current knowledge in the engineering of organoids, spheroids, or tissues (bone, liver, and heart among others) with and without scaffolds.

## Linked entities

- **Diseases:** lung cancer (MONDO:0005138), osteosarcoma (MONDO:0002623)

## Full-text entities

- **Genes:** GREM1 (gremlin 1, DAN family BMP antagonist) [NCBI Gene 26585] {aka C15DUPq, CKTSF1B1, CRAC1, CRCS4, DAND2, DRM}, VWF (von Willebrand factor) [NCBI Gene 7450] {aka F8VWF, VWD}, COL10A1 (collagen type X alpha 1 chain) [NCBI Gene 1300], Bmp4 (bone morphogenetic protein 4) [NCBI Gene 12159] {aka Bmp-4, Bmp2b, Bmp2b-1, Bmp2b1}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, Nanog (Nanog homeobox) [NCBI Gene 71950] {aka 2410002E02Rik, ENK, Stm1, ecat4}, RUNX2 (RUNX family transcription factor 2) [NCBI Gene 860] {aka AML3, CBF-alpha-1, CBFA1, CCD, CCD1, CLCD}, FOXO3 (forkhead box O3) [NCBI Gene 2309] {aka AF6q21, FKHRL1, FKHRL1P2, FOXO2, FOXO3A}, CD34 (CD34 molecule) [NCBI Gene 947], SOD2 (superoxide dismutase 2) [NCBI Gene 6648] {aka GC1, GClnc1, IPO-B, IPOB, MNSOD, MVCD6}, TF (transferrin) [NCBI Gene 7018] {aka HEL-S-71p, PRO1557, PRO2086, TFQTL1}, CD44 (CD44 molecule (IN blood group)) [NCBI Gene 960] {aka CDW44, CSPG8, ECM-III, ECMR-III, H-CAM, HCELL}, FGF4 (fibroblast growth factor 4) [NCBI Gene 2249] {aka FGF-4, HBGF-4, HST, HST-1, HSTF-1, HSTF1}, Notch1 (notch 1) [NCBI Gene 18128] {aka 9930111A19Rik, Mis6, N1, Tan1, lin-12}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, Pou5f1 (POU domain, class 5, transcription factor 1) [NCBI Gene 18999] {aka NF-A3, Oct-3, Oct-3/4, Oct-4, Oct3, Oct3/4}, SOX17 (SRY-box transcription factor 17) [NCBI Gene 64321] {aka PPH7, VUR3}, CCN2 (cellular communication network factor 2) [NCBI Gene 1490] {aka CTGF, HCS24, IBP-8, IGFBP8, KMD, NOV2}, Tpm1 (tropomyosin 1, alpha) [NCBI Gene 22003] {aka TM2, TPM1kappa, Tm3, Tmpa, Tpm-1, alpha-TM}, ATXN1 (ataxin 1) [NCBI Gene 6310] {aka ATX1, D6S504E, SCA1}, KIT (KIT proto-oncogene, receptor tyrosine kinase) [NCBI Gene 3815] {aka C-Kit, CD117, MASTC, PBT, SCFR}, CDH1 (cadherin 1) [NCBI Gene 999] {aka Arc-1, BCDS1, CD324, CDHE, ECAD, LCAM}, ALDH3B2 (aldehyde dehydrogenase 3 family member B2) [NCBI Gene 222] {aka ALDH8}, SOX2 (SRY-box transcription factor 2) [NCBI Gene 6657] {aka ANOP3, MCOPS3}, PROM1 (prominin 1) [NCBI Gene 8842] {aka AC133, CD133, CORD12, MCDR2, MSTP061, PROML1}, ACAN (aggrecan) [NCBI Gene 176] {aka AGC1, AGCAN, CSPG1, CSPGCP, MSK16, SEDK}, MMP13 (matrix metallopeptidase 13) [NCBI Gene 4322] {aka CLG3, MANDP1, MDST, MMP-13}, GATA4 (GATA binding protein 4) [NCBI Gene 2626] {aka ASD2, TACHD, TOF, VSD1}, PTEN (phosphatase and tensin homolog) [NCBI Gene 5728] {aka 10q23del, BZS, CWS1, DEC, GLM2, MHAM}, KDR (kinase insert domain receptor) [NCBI Gene 3791] {aka CD309, FLK1, VEGFR, VEGFR2}, S100A4 (S100 calcium binding protein A4) [NCBI Gene 6275] {aka 18A2, 42A, CAPL, FSP1, MTS1, P9KA}, ITGB1 (integrin subunit beta 1) [NCBI Gene 3688] {aka CD29, FNRB, GPIIA, MDF2, MSK12, VLA-BETA}, PECAM1 (platelet and endothelial cell adhesion molecule 1) [NCBI Gene 5175] {aka CD31, CD31/EndoCAM, GPIIA', PECA1, PECAM-1, endoCAM}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, MMP1 (matrix metallopeptidase 1) [NCBI Gene 4312] {aka CLG}, IHH (Indian hedgehog signaling molecule) [NCBI Gene 3549] {aka BDA1, HHG2}, YAP1 (Yes1 associated transcriptional regulator) [NCBI Gene 10413] {aka COB1, YAP, YAP-1, YAP2, YAP65, YKI}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, TAFAZZIN (tafazzin, phospholipid-lysophospholipid transacylase) [NCBI Gene 6901] {aka BTHS, CMD3A, EFE, EFE2, G4.5, LVNCX}, SHH (sonic hedgehog signaling molecule) [NCBI Gene 6469] {aka HHG1, HLP3, HPE3, MCOPCB5, SMMCI, ShhNC}, Prom1 (prominin 1) [NCBI Gene 19126] {aka 4932416E19Rik, AC133, CD133, Prom, Prom-1, Proml1}, NANOG (Nanog homeobox) [NCBI Gene 79923], HGF (hepatocyte growth factor) [NCBI Gene 3082] {aka DFNB39, F-TCF, HGFB, HPTA, SF}
- **Diseases:** nonalcoholic liver diseases (MESH:D065626), hepatitis (MESH:D056486), colon carcinoma (MESH:D003110), Breast CSCs (MESH:D001943), TS (MESH:D020914), MICROGRAVITY INFLUENCES DIFFERENTIATION (MESH:D012734), liver cirrhosis (MESH:D008103), follicular thyroid cancer (MESH:C572845), Cancer (MESH:D009369), diseases of the liver (MESH:D008107), acute liver failure (MESH:D017114), Non-small cell lung cancer (MESH:D002289), cirrhosis (MESH:D005355), rheumatoid arthritis (MESH:D001172), osteonecrosis (MESH:D010020), osteopenia (MESH:D001851), hypertrophy (MESH:D006984), liver failure (MESH:D017093), cartilage damage (MESH:D002357), alcohol misuse (MESH:D000437), metastasis (MESH:D009362), leukemia (MESH:D007938), STEM CELLS (MESH:D002292), CSCs (MESH:D018295), Gastrointestinal tumors (MESH:D005770), infection with hepatitis C and B viruses (MESH:D006509), hepatocellular carcinomas (MESH:D006528), deaths (MESH:D003643), Osteosarcoma (MESH:D012516), Bone loss (MESH:D001847), Lung cancer (MESH:D008175), tumorigenic (MESH:D002471), prostate cancer (MESH:D011471), lung CSCs (MESH:D055752), ischemic diseases (MESH:D017202), intervertebral disk damage (MESH:D055959), melanoma (MESH:D008545), Colorectal cancer (MESH:D015179), osteoarthritis (MESH:D010003), end-stage liver disease (MESH:D058625)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Sus scrofa (pig, species) [taxon 9823], Homo sapiens (human, species) [taxon 9606], Oryctolagus cuniculus (domestic rabbit, species) [taxon 9986], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** HO-1 — Homo sapiens (Human), Melanoma, Cancer cell line (CVCL_1E42), U87MGDu145 — Homo sapiens (Human), Glioblastoma, Cancer cell line (CVCL_0022), HepG2Human — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_0027), HOS — Homo sapiens (Human), Osteosarcoma, Cancer cell line (CVCL_0312), H7 — Bos taurus (Bovine), Spontaneously immortalized cell line (CVCL_HG38), FTC-133 — Homo sapiens (Human), Thyroid gland follicular carcinoma, Cancer cell line (CVCL_1219), LNCapH23Hep3bHelaMewo — Homo sapiens (Human), Buccal mucosa squamous cell carcinoma, Cancer cell line (CVCL_JB77), PICM-19 — Sus scrofa (Pig), Spontaneously immortalized cell line (CVCL_V146), H9 — Homo sapiens (Human), Sezary syndrome, Cancer cell line (CVCL_1240), IMR90 — Homo sapiens (Human), Finite cell line (CVCL_0347), H460 — Homo sapiens (Human), Lung large cell carcinoma, Cancer cell line (CVCL_0459), TZ-1 — Homo sapiens (Human), Acute monoblastic leukemia, Cancer cell line (CVCL_R882), SAOS-2 — Homo sapiens (Human), Osteosarcoma, Cancer cell line (CVCL_0548), SJ-10 — Homo sapiens (Human), Neuroblastoma, Cancer cell line (CVCL_1441), hFOB — Homo sapiens (Human), Conditionally immortalized cell line (CVCL_3708), U2OST98G — Channa striata (Snakehead murrel), Spontaneously immortalized cell line (CVCL_A2ZQ), HTC116 — Rattus norvegicus (Rat), Rat hepatocellular carcinoma, Cancer cell line (CVCL_3382), SJ — Mus musculus (Mouse), Conditionally immortalized cell line (CVCL_B463), HCT116 — Homo sapiens (Human), Colon carcinoma, Cancer cell line (CVCL_0291)

## Full text

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## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC7381804/full.md

## References

122 references — full list in the complete paper: https://tomesphere.com/paper/PMC7381804/full.md

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Source: https://tomesphere.com/paper/PMC7381804