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Prevention of multiple system atrophy using human bone marrow-derived mesenchymal stem cells by reducing polyamine
Kyung-Ran Park1, Chul Ju Hwang2, Hyung-Mun Yun1
1Department of Oral and Maxillofacial Pathology, School of Dentistry, Kyung Hee University, Seoul, 02453, Republic of Korea.
Background:
Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder of unknown etiology, but is closely associated with damage to dopaminergic neurons. MSA progression is rapid. Hence, long-term drug treatments do not have any therapeutic benefits. We assessed the inhibitory effect of mesenchymal stem cells (MSCs) on double-toxin-induced dopaminergic neurodegenerative MSA.
Results:
Behavioral disorder was significantly improved and neurodegeneration was prevented following MSC transplantation. Proteomics revealed lower expression of polyamine modulating factor-binding protein 1 (PMFBP1) and higher expression of 3-hydroxymethyl-3-methylglutaryl-CoA lyase (HMGCL), but these changes were reversed after MSC transplantation. In the in vitro study, the 6-OHDA-induced effects were reversed following co-culture with MSC. However, PMFBP1 knockdown inhibited the recovery effect due to the MSCs. Furthermore, HMGCL expression was decreased following co-culture with MSCs, but treatment with recombinant HMGCL protein inhibited the recovery effects due to MSCs.
Conclusions:
These data indicate that MSCs protected against neuronal loss in MSA by reducing polyamine- and cholesterol-induced neural damage.
