THE SERISM PROJECT FROM EARTH TO SPACE: STEP BY STEP
M. Maccarone, N. Battista, A. Gambacurta, M. Fava, S. Piccirillo, G. Valentini, G. Mascetti, M. Bari
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M. Maccarone: email@example.com
In the context of Space Medicine, the aim of “SERiSM” (Role of the Endocannabinoid System in Reprogramming human pluripotent Stem cells under Microgravity) project, selected by the Italian Space Agency, was to study the involvement of the Endocannabinoid System (ECS) in the osteogenic differentiation under real microgravity. An innovative and easily accessible stem cell model derived from human blood (human Blood-derived Stem Cells, hBDSCs) was used to this purpose. This model is autologous and possesses a remarkable proliterative and differentiative capacity under ground gravity conditions, with high therapeutic potential for bone degenerative diseases. ECS is a fine network of proteins that interact to regulate the endogenous levels of lipid mediators, collectively termed endocannabinoids (eCBs), which in turn are involved in cell communication and in the mechanisms governing the switch between cell life and death. In the frame of the VITA mission, led by European Space Agency (ESA) astronaut Paolo Nespoli, we analyzed the differentiation process also under microgravity condition, and evaluated the expression of ECS proteins through immunoassay methods. Our results demonstrate that some elements of the ECS are modulated during the differentiation process and in microgravity, supporting the idea that increased levels of anandamide are indeed need to stimulate type-1 cannabinoid receptor. in conclusion, microgravity could drive endocannabinoid signalling in the former stages of hBDSCs differentiation.
Endocannabinoid system; human Blood-derived Stem Cells; Microgravity; VITA mission.
- 1.Maccarrone M, Bab I, Bíró T, et al. Endocannabinoid signaling at the periphery: 50 years after THC. Trends in pharmacological sciences. 2015;36(5):277-296.
- 2.Bab I, Zimmer A. Cannabinoid receptors and the regulation of bone mass. British journal of pharmacology. 2008;153(2):182-188.
- 3.Deis S, Srivastava RK, de Azua IR, et al. Age-related regulation of bone formation by the sympathetic cannabinoid CB1 receptor. Bone. 2018;108:34-42.
- 4.Rossi F, Tortora C, Punzo F, et al. The endocannabinoid/endovanilloid system in bone: from osteoporosis to osteosarcoma. International journal of molecular sciences. 2019;20(8):1919.
- 5.Idris AI, Sophocleous A, Landao-Bassonga E, Van’t Hof RJ, Ralston SH. Regulation of bone mass, osteoclast function, and ovariectomy-induced bone loss by the type 2 cannabinoid receptor. Endocrinology. 2008;149(11):5619-5626.
- 6.Idris AI, van’t Hof RJ, Greig IR, et al. Regulation of bone mass, bone loss and osteoclast activity by cannabinoid receptors. Nature medicine. 2005;11(7):774-779.
- 7.Sophocleous A, Marino S, Kabir D, Ralston SH, Idris AI. Combined deficiency of the Cnr1 and Cnr2 receptors protects against age‐related bone loss by osteoclast inhibition. Aging Cell. 2017;16(5):1051-1061.
- 8.Battista N, Di Tommaso M, Norfini A, et al. Altered anandamide metabolism in microgravity: the “RESLEM” experiment. ISGP & ESA Life Sciences. Published online 2019:256.
- 9.Choukèr A, Kaufmann I, Kreth S, et al. Motion sickness, stress and the endocannabinoid system. PloS one. 2010;5(5):e10752.
- 10.Strewe C, Feuerecker M, Nichiporuk I, et al. Effects of parabolic flight and spaceflight on the endocannabinoid system in humans. Reviews in the Neurosciences. 2012;23(5-6):673-680.
- 11.Arianna C, Eliana C, Flavio A, et al. Rapid Rapamycin-only induced osteogenic differentiation of blood-derived stem cells and their adhesion to natural and artificial scaffolds. Stem Cells International. 2017;2017.
- 12.Gambacurta A, Merlini G, Ruggiero C, et al. Human osteogenic differentiation in Space: proteomic and epigenetic clues to better understand osteoporosis. Scientific reports. 2019;9(1):8343.