| First Author | Tachibana M | Year | 2018 |
| Journal | Exp Neurol | Volume | 300 |
| Pages | 13-21 | PubMed ID | 29106980 |
| Mgi Jnum | J:261233 | Mgi Id | MGI:6152997 |
| Doi | 10.1016/j.expneurol.2017.10.023 | Citation | Tachibana M, et al. (2018) Pericyte implantation in the brain enhances cerebral blood flow and reduces amyloid-beta pathology in amyloid model mice. Exp Neurol 300:13-21 |
| abstractText | Pericytes are a major component of cerebrovasculature playing a key role in maintaining cerebrovascular homeostasis. These cells have also been suggested to regulate brain metabolism of amyloid-beta (Abeta), disturbances of which are believed to contribute to the pathogenesis of Alzheimer''s disease (AD). To examine the effects of pericytes on brain Abeta metabolism, C3H/10T1/2 mouse mesenchymal stem cells were differentiated into pericytes and stereotaxically injected into the brains of amyloid AD model APP/PS1 mice at the age of 18 to 20months. Consistent with a role of pericytes in modulating cerebrovascular function, brain microcirculation in the pericyte-injected hemisphere of the mice was increased 3weeks after implantation compared to the contralateral hemisphere when measured by laser speckle contrast analysis technology. Importantly, enzyme-linked immunosorbent assay revealed that the levels of insoluble Abeta40 and Abeta42 were significantly lower in the hippocampus of the pericyte-injected hemisphere of the APP/PS1 mice than that of the contralateral side. Consistently, immunohistochemical analysis demonstrated that the pericyte implantation reduced Abeta deposition in the hippocampus. When brain slices from the APP/PS1 mice were incubated with C3H/10T1/2 cell-derived pericytes, Abeta42 levels were significantly reduced in a manner that depends on the expression of a major Abeta endocytic receptor, the low-density lipoprotein receptor-related protein 1 (LRP1). While LRP1 mediated the cellular uptake of Abeta in the pericytes, the amounts of major Abeta-degrading enzymes were not affected by LRP1 knockdown. Together, our findings indicate that mesenchymal stem cell-derived pericytes have the capacity to reduce brain Abeta and related pathology, and suggest that cell-based therapy through transplantation of pericytes may be a promising approach to prevent and/or treat AD. |
