Authors:

Jenna McLean

Date Created:

Not specified

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About Paper:

Microglia replacement is a promising new therapeutic for the treatment of multiple neurodegenerative diseases and brain tumors. Previous methods for microglia replacement require radiation or chemotherapy before microglia engraftment, leading to substantial adverse effects on patients. This study presents a simple and minimally invasive method to increase the success of microglia replacement and minimize adverse effects. We hypothesize that using an FDA approved microglia depletion drug PLX3397 before and after peripheral microglia transplantation will result in an empty niche in the central nervous system (CNS) that allows human- induced pluripotent stem cell-derived microglia progenitor cells to infiltrate into the CNS from the peripheral system and replace original microglia. Mice receive a first round of PLX administration through food consumption for 10 days. On the 10th day, mice receive a peripheral injection of progenitor cells. Mice then receive another 7 days of a lower concentration dose of PLX through oral gavage. Mice then undergo perfusion and samples are collected, stained, and analyzed. Results are processed through the sectioning and staining of the mouse brain. Mice who received PLX3397 and an injection of progenitor cells are compared with controls who did not receive PLX3397 or a progenitor cell injection. This comparison will provide insight into the efficacy of using a second round of PLX treatment and peripheral engraftment using human microglia progenitor cells for the intent of therapeutic techniques. Successful completion of this project will lead to a simple method for microglia-based cell therapy for the treatment of neurological disorders and brain tumors.

Source:

Purdue University / 2023

Topics:

No topics listed

Co-authors:

Jenna McLean