How does food influence our stem cells?

Stem cells in our bodies have a remarkable ability to stay undifferentiated while giving rise to specialized cells in response to our dietary requirements, maintaining tissue balance. Stem cells therapy requires high number of stem cells to be injected into the patients to treat certain kind of diseases and the only way to achieve this is by feeding the cells with a chemically defined ‘diet’ and provide an optimum condition for the cells to grow exponentially. The concept of feeding our body with food is similar to what the scientist ‘feed’ these mesenchymal stem cells in the lab. Nutrients derived from food contains bioactive compounds that are able to modulate gene expression and are capable of changing chromatin architecture acting on regulation of transcription factors. Factors such as mTOR, PPARG, RUNX2, SOX5/6/9 are among the key modulator of mesenchymal stem cell proliferation and differentiation into specialized cells to build bones, cartilage, muscles, skin and adipose tissues whenever is needed by our body.

Diagram showing differentiation programs of human mesenchymal stem cells into adipocytes, chondrocytes and osteoblasts in which each program is regulated by specific transcription factors. The image was reconstructed based on the the journal Effects of Nutrients, Mainly from Mediterranean Dietary Foods, on Mesenchymal Stem Derived Cells: Growth or Differentiation (2018).

Nutrients: It’s Role in Stem Cell Proliferation and Differentiation

Communication between stem cells with the surrounding cells through chemical signals known as cell niche, determine the stem cells fate for differentiation or self-renewal. Some nutrients may indirectly affect stem cell fate by changing the microenvironment through hormonal regulation. Alternatively, nutrients absorbed from carbohydrates, ketones, amino acids, lipids as well as phytochemicals may have direct effect towards stem cell self-renewal and differentiation . Simple carbohydrate like glucose and its metabolites, acetyl-CoA are responsible for maintaining pluripotency. Other types of carbohydrates may stimulate the PPARG receptor, which is responsible for adipogenesis. Several essential amino acids are reported to increase stem cell proliferation without affecting the stemness, even at higher abundance. Nutrients, such as vitamins, acts as modulators for genetic and epigenetic which consequently influences the behaviour of stem cells. Basically, the effect of diet on stem cells, both direct or indirect, could at least enhance one’s health and maintain stem cell count within an individual as opposed to stem cell therapy or transfusion where a greater number of stem cells are required for a particular treatment.

Although nutrient derived-metabolites obviously act as a cue for stem cell proliferation, the triggers have to be adequate for the cell division to start. Our body has a tight regulator known as mTORC1, which can sense nutrients and control balance between metabolism and cell fate. The amount of nutrient intake should be monitored as excessive or deficient nutrient uptake may cause long term impairment to stem cell functionality. For instance, a study on neonatal piglets have shown that calcium deficiency reduced mesenchymal stem cell proliferation to about 50%. Dietary restriction impairs bone marrow-derived stem cells proliferation on a short-term as well as long-term basis. This is because stem cells provide life-long supply of osteoprogenitors cells (main source of the new osteoblasts) and their proliferation rates are greatest during early infancy. On the other hand, a study in mouse models has shown that excessive alcohol consumption leads to reduced protein and bone mineral content which reduced osteogenic differentiation of stem cells. This leads to an increase in growth factors responsible for fats while causing a reduction of genes responsible for bone development.

Diets and the Impact on Stem Cells

Interestingly, different dieting methods such as restricting calory intake (frequent meal but 20-40% lesser in calory), fasting, keto diets (high fats, sufficient in protein and low in carbohydrate) and high fats diet can significantly affect stem cell function and microenvironment. Calory restriction enhances stem cell functionality, such as reversing age-related changes and improves mesenchymal proliferation rates. Fasting for 12-16 hours and refeeding substantially stimulates tissue regeneration through stem cells activation of certain signalling pathways. The refeeding process, which is lacking in calory restriction diet, is an important event where damage cells are replaced with new stem cell-derived cells. The impact of keto diets on adult stem cells is not well-documented, although historically, such diets have shown potential in protecting against neuron damage. However, prolonged high fat diets (more than 6 months) appear to increase intestine stem cells which is reported to cause tumorigenic effect.

Conclusion

Nutrients are crucial for all living organism for sustaining life. The quality, quantity and even the time we consume our food determines the fate of our stem cells. The ability to understand the effects of nutrients and calories on the multiple pathways taking place inside our body has led scientists to explore the possibility of manipulating pathways such as by delaying aging, improving organ regeneration as well as reprogramming adult stem cells into induced pluripotent stem cells (iPSC). Overall, in the fascinating interplay between nutrition and stem cells, we are unlocking new possibilities for enhancing health and regenerative medicine for the betterment of human lives.

References

Mahajan, A., Alexander, L. S., Seabolt, B. S., Catrambone, D. E., McClung, J. P., Odle, J., Pfeiler, T. W., Loboa, E. G., & Stahl, C. H. (2011). Dietary calcium restriction affects mesenchymal stem cell activity and bone development in neonatal pigs. Journal of Nutrition, 141(3), 373–379. https://doi.org/10.3945/jn.110.131193

Puca, F., Fedele, M., Rasio, D., & Battista, S. (2022). Role of diet in stem and cancer stem cells. International Journal of Molecular Sciences, 23(15), 8108. https://doi.org/10.3390/ijms23158108

Mana, M., Kuo, E. Y. S., & Yılmaz, Ö. H. (2017). Dietary regulation of adult stem cells. Current Stem Cell Reports, 3(1), 1–8. https://doi.org/10.1007/s40778-017-0072-x

Ammendola, S., Cocchiola, R. Lopreiato, M. & d’ Abusco, A.S. (2018). Effects of nutrients, mainly from Mediterranean dietary foods, on mesenchymal stem derived cells: growth or differentiation. International Journal of Clinical Nutrient & Dietetics, 4(131), 1-11. https://doi.org/10.15344/2456-8171/2017/122

Mehrabani, D., Masoumi, S.J., Masoumi, A.S., Rasouli-Nia, A., Karimi-Busheri, F. & Mehrabani, G. (2023). Role of diet in mesenchymal stem cells’ function: a review. International Journal of Nutrition Sciences, 8(1), 9-19. https://doi: 10.30476/IJNS.2023.97788.1221