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Melatonin and the Programming of Stem Cells

Published on Tuesday, 15 March 2022

Abstract

Melatonin interacts with various types of stem cells, in multiple ways that comprise stimulation of proliferation, maintenance of stemness and self-renewal, protection of survival, and programming toward functionally different cell lineages. These various properties are frequently intertwined but may not be always jointly present.

Melatonin typically stimulates proliferation and transition to the mature cell type. For all sufficiently studied stem or progenitor cells, melatonin's signaling pathways leading to expression of respective morphogenetic factors are discussed.

The focus of this article will be laid on the aspect of programming, particularly in pluripotent cells. This is especially but not exclusively the case in neural stem cells (NSCs) and mesenchymal stem cells (MSCs). Concerning developmental bifurcations, decisions are not exclusively made by melatonin alone. In MSCs, melatonin promotes adipogenesis in a Wnt (Wingless-Integration-1)-independent mode, but chondrogenesis and osteogenesis Wnt-dependently. Melatonin upregulates Wnt, but not in the adipogenic lineage. This decision seems to depend on microenvironment and epigenetic memory. The decision for chondrogenesis instead of osteogenesis, both being Wnt-dependent, seems to involve fibroblast growth factor receptor 3.

Stem cell-specific differences in melatonin and Wnt receptors, and contributions of transcription factors and noncoding RNAs are outlined, as well as possibilities and the medical importance of re-programming for transdifferentiation.

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About this publication.

- The Di Bella Method (A Fixed Part - Melatonin tablets. From 30-40mg/day up to 200mg/day orally in patients with advanced stage of cancer disease and/or patients without respond to traditional treatments);

- Melatonin use in cancer patients have started in 1974, when melatonin prepared according to Prof. Di Bella’s formulation [...]. For 11 days was administered to the patient, admitted to the general medical ward at the Maggiore-Pizzardi Hospital in Bologna, very slowly (over approx. 8 hours) and intravenously administered 1000 mg of melatonin for 11 days. During the course of each day, the patient was intravenously administered 4 saline drips of 500 ml, each containing ten 25 mg bottles of freeze-dried melatonin, lasting 2 hours, totaling 1000 mg per day. No other drug of any kind was administered in order to ascertain the effect of the MLT without interference [...]. From Melatonin with adenosine solubilized in water and stabilized with glycine for oncological treatment - technical preparation, effectivity and clinical findings;

- About Melatonin - In vitro, review and in vivo publications;

- Publication: Melatonin anticancer effects: Review (from Di Bella's Foundation);

- Publication: Key aspects of melatonin physiology: 30 years of research (from Di Bella's Foundation);

- The Di Bella Method (A Fixed Part - Cyclophosphamide 50mg tablets and/or Hydroxyurea 500mg tablets, one or two per day);

- The Di Bella Method (A Fixed Part - Calcium, 2 grams per day, orally);

- The Di Bella Method (A Fixed Part - Bromocriptine and/or Cabergoline);

- Prolactin inhibitors in oncology - In vitro, review and in vivo publications;

- The Di Bella Method (A Fixed Part - Somatostatin, Octreotide, Sandostatin LAR, analogues and/or derivatives);

- Somatostatin in oncology, the overlooked evidences - In vitro, review and in vivo publications;

- Publication, 2018 Jul: Over-Expression of GH/GHR in Breast Cancer and Oncosuppressor Role of Somatostatin as a Physiological Inhibitor (from Di Bella's Foundation);

- Publication, 2018 Sep: The over-expression of GH/GHR in tumour tissues with respect to healthy ones confirms its oncogenic role and the consequent oncosuppressor role of its physiological inhibitor, somatostatin: a review of the literature (from Di Bella's Foundation);

- Publication, 2019 Aug: The Entrapment of Somatostatin in a Lipid Formulation: Retarded Release and Free Radical Reactivity (from Di Bella's Foundation);