Bone Marrow Stromal Stem Cells Induce Autophagy That May Exert Neuroprotective Effects

Purpose: Bone marrow stromal cells (BMSCs) are self-renewing, multipotent cells that can migrate to pathological sites, making them a promising therapeutic tool for neurodegenerative disorders. However, the therapeutic mechanisms by which they act are largely unknown, although cell replacement and paracrine mechanisms have been hypothesized. The objective of this work was to determine the ability of rat BMSCs to induce autophagy and whether this effect provides neuroprotection. Methods: We co-cultured BMSCs with rotenone-exposed SH-SY5Y cells overexpressing alpha-synuclein, and examined whether BMSCs could induce autophagy. Results: The BMSC coculture led to increased expression of autophagy markers, such as the microtubule-associated protein light chain 3 II (LC3II) and Beclin1, and decreased levels of alpha-synuclein in A53T mutant cells. This suggests that BMSCs can induce autophagy and that this effect may enhance the clearance of aggregated alpha-synuclein. In addition, BMSCs were also found to protect against rotenone-induced SH-SY5Y cell injury and apoptosis, and this effect became enhanced following rapamycin treatment and was partially decreased following treatment with the autophagosome inhibitor 3-methyladenine (3-MA). Conclusion: Ultimately, we conclude that BMSCs induce autophagy, an effect which may have neuroprotective benefits. BMSC transplantation is a potentially effective strategy to treat diseases associated with aggregated proteins, such as Parkinson's disease (PD).