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In addition, functional MSCs were isolated as a result from induced Pluripotent Stem Cell (iPS) manipulation, although further researches are necessary to assess both safety and affordability of this method ( 36-38).
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To date, prolonged hMSC lifespan, as well as a reduction of senescent phenotypes, have been obtained with the inhibition of the hystone acetyltransferase ( 28), the reduction of oxidative stress ( 29-31), using antagonists of the lysophosphatidic acid (LPA) receptor pathway ( 32), and culturing hMSCs with rapamycin ( 33-35). Research is looking for new stimuli to modulate stemness and aging pathways to slow down cellular senescence in culture and for new ways to collect hMSCs. Therefore, increased attention has been focused on hMSCs to improve their in vitro expansion in order to counteract, and possibly reverse their natural senescence process. Unfortunately stem cells, as well as all cultured primary cells ( 18), undergo cellular senescence along culture passages, with substantial decline in their differentiation and self-renewal potential ( 17, 19, 20). Therefore, cell-based therapy protocols generally require hundreds of million hMSCs per treatment and, consequently, they are subjected to long-term expansion ex vivo, in order to obtain a large amount of cells prior to transplantation ( 17). Although hMSCs are present in many tissues, they are few in number. The peculiar characteristics of these cells make them amenable in a wide range of cell-based therapies, including clinical applications for many diseases, such as graft-versus-host disease, periodontitis, severe chronic myocardial ischemia, liver cirrhosis, multiple sclerosis and diabetes ( 2, 12-16). In conclusion, hASCs exposure to ZF1 is a feasible tool to counteract and reverse human stem cell senescence in long-term culturing conditions.ĭuring the human life, hMSCs play an important role in replacing old or damaged cells, in order to preserve tissue integrity and oppose senescence-related processes ( 6-11). Both osteogenic and adipogenic abilities were enhanced. Increased telomerase activity was associated with TERT overexpression. Both stemness ( NANOG, OCT4, and MYC) and anti-senescence ( BMI1, and telomerase reverse transcriptase - TERT) related genes were overexpressed at specific experimental points, without recruitment of the cyclin-dependent kinase Inhibitor 2A ( CDKN2A, alias p16). Exposure to ZF1 strongly reduced the expression of senescence marker beta-galactosidase. Here, we show that an extract from early Zebrafish embryo (ZF1) counteracted senescence progression in human adipose-derived stem cells (hASCs) along multiple culture passages (from the 5 th to the 20 th). Unfortunately, prolonged culture leads to cell senescence, a major drawback from successful outcomes in cell therapy approaches.
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They are usually expanded for multiple passages in vitro to increase cell yield prior to transplantation. Human adult stem cells hold promise for regenerative medicine.