MOLECULAR ASPECTS OF THERAPEUTIC ACTION OF 3° TRIMESTER AMNIOTIC FLUID CELLS IN A MOUSE MODEL OF SPINAL CORD INJURY
Tesi di Dottorato
Data di Pubblicazione:
2014
Citazione:
MOLECULAR ASPECTS OF THERAPEUTIC ACTION OF 3° TRIMESTER AMNIOTIC FLUID CELLS IN A MOUSE MODEL OF SPINAL CORD INJURY / G. Scesa ; tutor: A. Gorio ; coordinatore: A. Gorio. Università degli Studi di Milano, 2014 Dec 11. 27. ciclo, Anno Accademico 2014. [10.13130/scesa-giuseppe_phd2014-12-11].
Abstract:
Spinal cord injury (SCI) is a disabling degenerative disease that heavily impacts on patient's life. To date, treatments available are mostly vain, thought to target the inflammatory processes sustaining the secondary damage: in this scenario, the use of stem cells represents a promising new therapeutic strategy as it might permit a complete recovery of the patient through a regeneration of damaged nerve fibers. Among the different type of stem cells available, we focused on 3° trimester amniotic fluid-derived cells (Afs), verifying their potential therapeutic activity on a mouse model of SCI.
Only the cultures expressing NG2 were able to elicit an improvement in the motor performance, obtained through a better preservation of damaged tissue. It was observed a higher angiogenesis in the perilesion area, sustained by an upregulation of the pro-angiogenic genes HIF-1α and VEGF; furthermore macrophage infiltration levels were significantly reduced in cells treated mice compared to controls. The Hepatocyte Growth Factor (HGF) mRNA and protein levels resulted higher in the filtering organs, as the lungs, and in the bloodstream of transplanted animals, suggesting an endocrine effect of the cells.
The ability of the cells to produce HGF was confirmed in vitro, after stimulation with proinflammatory cytokines, like IL1-β and LPS, suggesting the cells might be responsive to an environment-induced activation.
Given these results, AFs demonstrated to exert a therapeutic effect in our animal model of spinal cord injury.
Tipologia IRIS:
Tesi di dottorato
Keywords:
Stem cells; regenerative medicine; spinal cord injury
Elenco autori:
G. Scesa
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