Stem cell fusion as an ultimate line of defense against xenobiotics.
There are several indications that the potential of stem cells to fuse with somatic cells is extremely high and, what's more exciting, in some instances goes as far as reprogramming and/or rescuing altered cells. It remains unclear, however, how frequent this mechanism is and what patho-physiological role it might play in nature. A plausible hypothesis, discussed in this paper, suggests that stem cell niches might provide a safeguard for the intact genome and epigenome. By fusing with somatic de-differentiated cells, stem cells might consent epigenetic reprogramming and/or genetic recovery of genes which otherwise could drive altered cells to malignancy. If the many sophisticated mechanisms of metabolism, cell repair, programmed cell death and tissue regeneration should fail, stem cells might represent a final attempt to recover dedifferentiated cells to avoid inflowing in cancer. In the current reappraisal of the different mechanisms of defense against xenobiotics, even the incidence of cancer itself is considered an evolving mechanism which, through a kind of programmed death of individuals exhibiting defective mutations, favors advancement of the phenotypes which adapt best. Additionally, with regard to the mechanisms of transmitting somatic mutations, based on stem cells' capacity to migrate and to fuse, here it is speculated that stem cells might be capable of carrying acquired somatic mutations from peripheral tissues to the gonads, and transmit that information into the germinal line. If appropriately demonstrated, these mechanisms might delineate a novel therapeutic area to be explored. The use of stem cells to reprogram/recover irreversibly damaged cells or to transmit beneficial mutations might be a valuable therapeutic approach in the future.
Padron Velazquez
Julio Lazaro
JL
Department of Pharmacology, Istituto di Ricerche di Biologia Molecolare P. Angeletti, Merck Sharp and Dohme Research Laboratories, Via Pontina KM 30.600, Pomezia 00040, Rome, Italy. julio_padron@merck.com
D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D002459:Cell Fusion; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D006801:Humans; D009154:Mutation; D012038:Regeneration; D013234:Stem Cells / Q000502:physiology*; D015262:Xenobiotics / Q000037:antagonists & inhibitors*
D015262:Xenobiotics