Assessment of the human mesenchymal stem cells structural and functional characteristics associated to a prolonged exposure of morphine.

The discovery of opioid receptors expression in skin and their role in orchestrating the tissue repairing process, gave rise to questions regarding the potential effects of clinical morphine treatment in wound healing. Although short term treatment was reported to improve wounds regeneration, in vivo chronic administration was associated to immune cell recruitment delay and abnormal extracellular matrix deposition, impairing the physiological tissue healing progression and causing systemic fibrosis. Human mesenchymal stem cells (hMSCs) are a versatile class of multipotent adult stem cells. Their self-renew and multidirectional differentiation ability, combined with the release of immunoregulatory molecules, make them fundamental in restoring the damaged tissues. In this regard, opioid receptors expression was recently observed even in hMSCs[1], for which acute morphine exposition induced a significant functional characteristics decline[2]. However still little is known about its long-term effects. To determine how a prolonged treatment could impair their regenerative potential, we exposed hMSCs to increasing morphine concentrations respectively for nine and eighteen days, evaluating in particular the fibrogenic potential. Our results showed a time dependent cell viability decline and conditions compatible with a cellular senescent state. Ultrastructural analysis combined with beclin-1 (BECN1) and microtubuleassociated proteins 1A/1B light chain 3B (LC3) expression, after eighteen days of exposition, were indicative of increased autophagy, suggesting a correlation to an augmented detoxification activity. In addition, the enhanced transcription of type I collagen (COL1A1) together with the related genes involved in its regulation, namely: metalloproteinase-1 and -2 (MMP1, MMP2), transforming growth factor-beta1 (TGFB1) and tumour necrosis factor-alpha (TNFA), suggested the possibility that a prolonged morphine treatment might exert its fibrotic potential risk even involving the hMSCs. [ABSTRACT FROM AUTHOR]