Int J Med Sci 2020; 17(5):657-663. doi:10.7150/ijms.41515 This issue


Exosomes from Human Periapical Cyst-MSCs: Theranostic Application in Parkinson's Disease

Marco Tatullo1,2✉, Benedetta Marrelli1,2✉, Maria Josephine Zullo3#, Bruna Codispoti1, Francesco Paduano1, Caterina Benincasa1, Francesco Fortunato4#, Salvatore Scacco5#, Barbara Zavan6#, Tiziana Cocco5#

1. Marrelli Health - Tecnologica Research Institute, Biomedical Section, Street E. Fermi, Crotone, Italy
2. Department of Therapeutic Dentistry, Sechenov University Russia, Moscow, Russia
3. Department of Internal Medicine, Lausanne University Hospital, Lausanne, Switzerland
4. Department of Neurological Sciences, University of Catanzaro “Magna Graecia”, Italy
5. Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari “Aldo Moro”, Italy
6. Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
#Equal contribution

This is an open access article distributed under the terms of the Creative Commons Attribution License ( See for full terms and conditions.
Tatullo M, Marrelli B, Zullo MJ, Codispoti B, Paduano F, Benincasa C, Fortunato F, Scacco S, Zavan B, Cocco T. Exosomes from Human Periapical Cyst-MSCs: Theranostic Application in Parkinson's Disease. Int J Med Sci 2020; 17(5):657-663. doi:10.7150/ijms.41515. Available from

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The scientific community continuously strives to get new disease models, to discover early markers or novel therapeutic approaches, improving the diagnosis and prognosis of several human pathologies. Parkinson's Disease (PD) is characterized by a long asymptomatic phase, characterized by a selective loss of dopaminergic neurons. Recently, the human Periapical Cyst-Mesenchymal Stem Cells (hPCy-MSCs) have been differentiated in functional dopaminergic neurons: such oral-derived MSCs and the hPCy-MSCs-derived exosomes may represent a strategic and useful in vitro study-model, as well as intriguing therapeutic carriers. Circadian rhythm (CR) alteration variously impacts on PD pathways: an interesting research target is represented by the analysis of the exosomes released by dopaminergic neurons, derived from neural-differentiated hPCy-MSCs, after having reproduced in-vitro PD-like conditions. This review aims to describe the crosstalk among some aspects of circadian rhythm related to the onset of PD and the exosomes released by cells of PD patients. More in detail: the first part of this article will describe the main characteristics of circadian rhythm and the involvement of the exosomes found to be effective in the pathogenesis of PD. Finally, the authors will suggest how those exosomes derived from dopaminergic neurons, obtained by oral-derived stem cells (hPCy-MSCs) may represent a smart model for the in vitro research on PD, to find new biomarkers, to test new drugs or, fatally, to find new pathways applicable in future therapeutic approaches.

Keywords: exosomes, circadian rhythm, Parkinson's Disease