To assess the specificity of homing, we downregulated PDGFRB a key pericyte surface receptor involved in cell adhesion in iPSC-pericytes (using siRNA), which resulted in reduced homing.
Comments
Log in with your Bluesky account to leave a comment
Next, we confirmed a functional iPSC-pericyte–vasculature association using a proximity ligation assay (PLA) targeting two known pericyte–endothelium interactions: PDGF-BB/PDGFRB and vitronectin/ITGA5
To assess if the homing effect can be also seen in vivo, we next transplanted iPSC-pericytes into the hippocampi of pericyte-deficient mice. Similar to the ex vivo results, we confirmed that iPSC-pericytes can home to brain capillaries of mice in vivo
Functionally, iPSC-pericyte transplantation locally restored BBB integrity and promoted neuronal survival in the hippocampus of pericyte-deficient mice
Since mouse pericytes have been shown to clear Aβ and tau from the brain, we showed that our iPSC-pericytes are also capable of clearing Aβ and tau, and that this clearance is dependent on the lipoprotein receptor LRP1, a major Aβ clearance receptor.
Comments
https://www.biorxiv.org/content/10.1101/2023.06.26.546577v2