@rrust.bsky.social
Asst Prof at @keckmedicineusc.bsky.social with interest in the #brain, #BBB, #stemcells and what can go wrong following #stroke & #AD. π§ π¬ Alumni of @ethzurich.bsky.social
Delayed Transplantation (7 vs 1 dpi) of #NeuralStemCell Improves Initial Graft Survival after #Stroke
β«graft axon extension along #CorpusCallosum to contralateral hemisphere
@ctackenberg.bsky.social @rrust.bsky.social #AdvSci 2025
advanced.onlinelibrary.wiley.com/doi/10.1002/...
"Authentic" #hiPSC-derived #Pericyte π
Sharing highly similar proteome/phosphoproteome to primaryπ€π§ cortical pericyte
Contractile
β« #BloodBrainBarrier & Neuroprotective (Pdgfrb F7/F7π)
Clear AΞ² Tau (π§ slices 5xFADπ APOE4 P3001Sπ)
@rrust.bsky.social bioRxiv 2025
www.biorxiv.org/content/10.1...
#hiPSC derived #Pericyte
π>80% Home to & >50% Arborize on Capillaries in liveπ§ slice of PdgfrbF7/F7π
in situ PDGFBB-PDGFRΞ² PLA assayπ
πβ«AmyloidΞ² clearance on 10-m/o 5xFAD ππ§ slice
Are these phagocytic pericytes still vessel-bound?π
@rrust.bsky.social bioRxiv 2025
www.biorxiv.org/content/10.1...
In @nature.com we describe the use of scalable #proteinengineering & #machinelearning to predict millions of bespoke CRISPR enzymes, offering safer & more efficient genome editing tools π§¬π₯οΈ @rachelsilverstein9.bsky.social @mgbresearch.bsky.social @harvardmed.bsky.social
www.nature.com/articles/s41...
cellular and molecular shifts in the brain during the repair phase
#Medskyπ§ͺ #Neurosky Much of stroke research focuses on acute injury - but what changes in the brain one month after stroke? By @rrust.bsky.social et l
link.springer.com/article/10.1...
www.researchhub.com/paper/938498...
Interesting finding that neural stem cells exist outside the brain/spinal cord-in tissues like lung & tail-and share key properties with brain NSCs, challenging current dogma.
Wonder if these NSCs exist in humans & can show similar therapeutic potential
www.nature.com/articles/s41...
Check out the preprint, we appreciate any feedback:
www.biorxiv.org/content/10.1...
Since mouse pericytes have been shown to clear AΞ² and tau from the brain, we showed that our iPSC-pericytes are also capable of clearing AΞ² and tau, and that this clearance is dependent on the lipoprotein receptor LRP1, a major AΞ² clearance receptor.
10.04.2025 23:09 β π 1 π 0 π¬ 1 π 0
Functionally, iPSC-pericyte transplantation locally restored BBB integrity and promoted neuronal survival in the hippocampus of pericyte-deficient mice
10.04.2025 23:09 β π 0 π 0 π¬ 1 π 0To 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
10.04.2025 23:09 β π 0 π 0 π¬ 1 π 0
Next, we confirmed a functional iPSC-pericyteβvasculature association using a proximity ligation assay (PLA) targeting two known pericyteβendothelium interactions: PDGF-BB/PDGFRB and vitronectin/ITGA5
10.04.2025 23:09 β π 0 π 0 π¬ 1 π 0To 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.
10.04.2025 23:09 β π 0 π 0 π¬ 1 π 0Then we asked whether iPSC-pericytes can home to brain capillaries in host brains with reduced pericyte coverage. We added our cells to live brain slices of pericyte-deficient mice
10.04.2025 23:09 β π 0 π 0 π¬ 1 π 0
Next we show iPSC-pericytes help with the formation of blood-brain barrier tight junction proteins in human brain endothelial cells.
10.04.2025 23:09 β π 0 π 0 π¬ 1 π 0
We first compared iPSC-pericytes and primary pericytes using proteomics/phosphoproteomics and found no major differencesβiPSC-PC shared 96% of proteins and 98% of phosphopeptides, including key markers, adhesion proteins, and TFs.
10.04.2025 23:09 β π 0 π 0 π¬ 1 π 0New preprintπ¨ We generated human brain pericytes from pluripotent stem cells. They show strong molecular & functional similarities to primary human brain pericytes
Transplanted into pericyte-deficient mice, they formed hybrid human-mouse microvesselsπ
biorxiv.org/content/10.1...
Dynamic structural connectivity changes in cortical and cortico-striatal strokes in mice https://www.biorxiv.org/content/10.1101/2025.03.27.644898v1
29.03.2025 07:15 β π 2 π 1 π¬ 0 π 0
We also discuss few recent studies using e.g. gene and cell therapies to improve BBB integrity and neuronal function and much more!
25.03.2025 16:14 β π 0 π 0 π¬ 0 π 0
So how can we protect or modify BBB function in AD?
One option is to enhance the clerance function for neurotoxic proteins at the BBB e.g. targeting lipoprotein receptors (LRP)
BBB breakdown can significantly affect neuronal and synaptic function and neurodegenerative processes.
We think that more attention should focus on therapeutics to preserve BBB functions when considering treatments of neurodegenerative diseases including AD.
A new review from our lab exploring how the blood-brain barrier (BBB) can be used as a treatment target for neurodegenerative disorders
tandfonline.com/doi/10.1080/...
TL;DR β Here are a few key highlights π
Here's a very cool paper from @biorxiv-biophys.bsky.social I shared on ResearchHub this week. The authors designed a three-legged motor protein that can walk down DNA in either direction. www.researchhub.com/paper/930685... π§ͺ @researchhubf.bsky.social
18.03.2025 17:50 β π 14 π 5 π¬ 3 π 0
Optimize the time window for cell therapy for #Stroke
Photothrombosis
Rag2-/-π
hiPSC-#NeuralProgenitorCell
intracerebral injection
7 days (vs 1 d) post injuryβ‘οΈ
β«NPC proliferation
~20-foldβ«survival by 7-wk dpiπ
@rrust.bsky.social bioRxiv 2025
www.biorxiv.org/content/10.1...
Do our genes sabotage our bodies?
@haoyin.bsky.social reviewed a bioRxiv paper that suggests a special gene helps melanoma (a type of skin cancer) grow and evade the immune system. π§΅1/7
Nice roundup on CRISPR genome editing @economist.com
www.economist.com/leaders/2025...
#Medskyπ§ͺ #IDsky #Immunosky #publichealth the study showed that rising self-antigen levels during infection give self-reactive #Tcells an opportunity for enhanced TCR signalling. Regulatory T cells of matched specificity counteract this thatβs preventing autoimmunity.
www.science.org/doi/10.1126/...
Very cool! Thanks for sharing βΊοΈ
22.02.2025 15:10 β π 1 π 0 π¬ 0 π 0@kevinbonham.com thanks Kevin! Did it myself, always happy to contribute to some work if you need similar illustrations! βΊοΈ
22.02.2025 03:16 β π 3 π 0 π¬ 1 π 0
Is this real? I published it again on Brain @brain1878.bsky.social π
Truly appreciate the leadership of @rrust.bsky.social on this great project (>300 refs!)π«‘π
The bloodβbrain barrier: a help & a hindrance
#Aging #Stroke #Neurodegeneration
Crossing #BBB π
academic.oup.com/brain/advanc...
New review from our lab in
@brain1878.bsky.social
We explore how molecular blood-brain barrier (BBB) changes in aging, neurodegeneration and stroke affect disease progression, delivery of therapeutics, and much more!
academic.oup.com/brain/advanc...
