Stem Cells in Microgravity: The Future of Tissue Engineering

Stem cell therapy is one of regenerative medicine’s most promising modalities. Microgravity provides a uniquely supportive environment for stem cell research and production. 

Microgravity encourages cellular expansion while reducing differentiation, enabling advancements that would be difficult or impossible under ordinary conditions (Ghani, 2024). Simulated microgravity can further the state-of-the-art by enhancing the commercial and therapeutic viability of stem cells. 

Microgravity-Driven Heart Tissue Engineering

Cardiovascular disease accounted for over 30% of all deaths in 2019 (CDC, n.d.). The need for new treatments makes cardiac tissue engineering a high-priority. However, lab-grown heart cells must achieve developmental milestones, such as proper contraction and electrical signaling, to be viable. 

Zimmermann et al. combined young rat heart cells with collagen, forming ring structures and applying mechanical stretching. This method produced engineered heart tissue with key features of mature cardiac muscle (Zimmermann, 2002).

Microgravity may significantly affect heart cell development. The International Space Station (ISS) used human stem cell-derived heart cells to assess how microgravity might support heart tissue engineering. These unique conditions facilitated stem cell differentiation into functional heart muscle cells, yielding cells with qualities closely resembling natural cardiac tissue (Ma, 2014). 

Additionally, 3D scaffolds within rotating culture systems allow for more natural heart tissue formation, creating tissue structures that mimic real heart muscle more effectively than traditional lab settings (Grimm, 2020).

Shinde et al. demonstrated that simulated microgravity encourages embryonic stem cells to become heart muscle cells by modulating differentiation pathways. Learning how to influence cell specialization could ultimately lead to lab-grown heart tissue engineered to alleviate cardiac conditions (Shinde, 2016).

Microgravity-Driven Liver Tissue Engineering

Every year liver disease claims 2 million lives worldwide. Cirrhosis and liver cancer ranking among the most common causes of death (Asrani, 2018). 

With a 3D clinostat—a device that simulates microgravity— stem cell growth doubled without causing cellular damage. Within days, key proteins such as BMP4 and Notch1 drove these cells to differentiate into liver cells—blocking BMP4 halted this process (Majumder, 2011). 

Further studies have examined how microgravity impacts liver cancer cells (HepG2) and bile duct stem cells (hBTSCs), where both cell types fortuitously form complex 3D structures, showing increased activity in genes related to “stemness”—instrumental to therapeutic use (Costantini, 2019). 

Cellular metabolism was also altered—changing glucose consumption and waste production—essential for refining liver tissue engineering methods (Costantini, 2019).

Microgravity-Driven Cartilage Tissue Engineering

In 2020 the global population over 60 surpassed the population under five, and is expected to double by 2050 (WHO, 2023). This demographic shift underscores the importance of new treatments for conditions like arthritis and spinal disc damage, which become all too common with age. 

Due to its poor blood supply, cartilage does not readily self-repair and tends to break down rather than rebuild (Hunziker, 2002).

Regenerative medicine has thus turned to stem cells for new approaches to cartilage repair. Studies indicate that low-gravity environments enhance the development of cartilage-like tissue from bone marrow and fat-derived stem cells. 

For instance, Ohyabu et al. successfully cultivated cartilage tissue from rabbit mesenchymal stem cells in a rotating bioreactor to mimic low-gravity conditions, creating tissue with genetic markers and structural qualities similar to cartilage made in vivo (Ohyabu, 2006).

Further research by Yuge et al. on human stem cells showed that cells grown in a 3D clinostat multiplied 13 times in a week, compared to the control group’s 4. Remarkably, these cells maintained their telomere length, a marker of cellular aging, in both environments. 

When transplanted into mice with cartilage defects, the microgravity-grown cells formed healthy cartilage within a week, an outcome not seen in cells cultured under ordinary conditions (Yuge, 2006). 

The Road Ahead

Litegrav is a pivotal player in advancing this frontier. Its solutions, including simulated microgravity, provide researchers with the tools they need to mimic extreme conditions. This allows for the rapid and cost-effective exploration of a vast array of biological processes, including stem cell growth, tissue engineering, and regenerative medicine. 

By offering scalable, controlled microgravity environments, Litegrav allows for rigorous, high-throughput studies that can optimize cell differentiation and tissue formation. Despite its long history, dating back to the 1940s, microgravity research is still young. Its results are too extraordinary to ignore. 

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References and Works Cited:

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Asrani SK, Devarbhavi H, Eaton J, Kamath PS. Burden of liver diseases in the world. J Hepatol. 2019 Jan;70(1):151-171. doi: 10.1016/j.jhep.2018.09.014. Epub 2018 Sep 26. PMID: 30266282.

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Clevers, H. Cancer therapy: Defining stemness. Nature 534, 176–177 (2016). https://doi.org/10.1038/534176a

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Costantini D, Overi D, Casadei L, Cardinale V, Nevi L, Carpino G, Di Matteo S, Safarikia S, Valerio M, Melandro F, Bizzarri M, Manetti C, Berloco PB, Gaudio E, Alvaro D. Simulated microgravity promotes the formation of tridimensional cultures and stimulates pluripotency and a glycolytic metabolism in human hepatic and biliary tree stem/progenitor cells. Sci Rep. 2019 Apr 3;9(1):5559. doi: 10.1038/s41598-019-41908-5. PMID: 30944365; PMCID: PMC6447605.

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Ghani, F., Zubair, A.C. Discoveries from human stem cell research in space that are relevant to advancing cellular therapies on Earth. npj Microgravity 10, 88 (2024). https://doi.org/10.1038/s41526-024-00425-0

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Grimm D, Wehland M, Corydon TJ, Richter P, Prasad B, Bauer J, Egli M, Kopp S, Lebert M, Krüger M. The effects of microgravity on differentiation and cell growth in stem cells and cancer stem cells. Stem Cells Transl Med. 2020 Aug;9(8):882-894. doi: 10.1002/sctm.20-0084. Epub 2020 Apr 30. PMID: 32352658; PMCID: PMC7381804.

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Hunziker EB. Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. Osteoarthritis Cartilage. 2002 Jun;10(6):432-63. doi: 10.1053/joca.2002.0801. PMID: 12056848.

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Ma X, Pietsch J, Wehland M, Schulz H, Saar K, Hübner N, Bauer J, Braun M, Schwarzwälder A, Segerer J, Birlem M, Horn A, Hemmersbach R, Waßer K, Grosse J, Infanger M, Grimm D. Differential gene expression profile and altered cytokine secretion of thyroid cancer cells in space. FASEB J. 2014 Feb;28(2):813-35. doi: 10.1096/fj.13-243287. Epub 2013 Nov 6. PMID: 24196587.

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Majumder S, Siamwala JH, Srinivasan S, Sinha S, Sridhara SR, Soundararajan G, Seerapu HR, Chatterjee S. Simulated microgravity promoted differentiation of bipotential murine oval liver stem cells by modulating BMP4/Notch1 signaling. J Cell Biochem. 2011 Jul;112(7):1898-908. doi: 10.1002/jcb.23110. PMID: 21433062.

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Ohyabu Y, Kida N, Kojima H, Taguchi T, Tanaka J, Uemura T. Cartilaginous tissue formation from bone marrow cells using rotating wall vessel (RWV) bioreactor. Biotechnol Bioeng. 2006 Dec 5;95(5):1003-8. doi: 10.1002/bit.20892. PMID: 16986169.

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Shinde V, Brungs S, Henry M, Wegener L, Nemade H, Rotshteyn T, Acharya A, Baumstark-Khan C, Hellweg CE, Hescheler J, Hemmersbach R, Sachinidis A. Simulated Microgravity Modulates Differentiation Processes of Embryonic Stem Cells. Cell Physiol Biochem. 2016;38(4):1483-99. doi: 10.1159/000443090. Epub 2016 Apr 4. PMID: 27035921.

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World Health Organization. (2023). Ageing and health. https://www.who.int/news-room/fact-sheets/detail/ageing-and-health

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World Health Organization. (n.d.). Cardiovascular diseases (CVDs). WHO. Retrieved November 11, 2024, from https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds)

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