Ruslan Rust

Can stem cells help to regain brain function after stroke?

Our new study in NatureComms @natureportfolio.nature.com shows that they can and dissect the key mechanisms driving recovery.

t.co/KRfAHfkNIH

Effects of psilocybin and related compounds on neuroprote... Effects of psilocybin and related compounds on neuroprotection...

Effects of psilocybin and related compounds on neuroprotection in human stroke www.researchhub.com/fund/4261/ef...

Delayed Transplantation (7 vs 1 dpi) of #NeuralStemCell Improves Initial Graft Survival after #Stroke

⏫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 😎

Sharing highly similar proteome/phosphoproteome to primary👤🧠cortical pericyte

Contractile

⏫ #BloodBrainBarrier & Neuroprotective (Pdgfrb F7/F7🐭)

Clear Aβ Tau (🧠slices 5xFAD🐭 APOE4 P3001S🐭)

@rrust.bsky.social bioRxiv 2025
www.biorxiv.org/content/10.1...

#hiPSC derived #Pericyte

👉>80% Home to & >50% Arborize on Capillaries in live🧠slice of PdgfrbF7/F7🐭
in situ PDGFBB-PDGFRβ PLA assay😍

👉⏫Amyloidβ clearance on 10-m/o 5xFAD 🐭🧠slice
Are these phagocytic pericytes still vessel-bound?😁

@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 🧬🖥️ @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

#Medsky🧪 #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...

Multipotent neural stem cells originating from neuroepithelium exist outside the mouse central nervous system - Nature Cell Biology Han et al. report the existence of neural stem cells (NSCs) outside the central nervous system and show that these peripheral NSCs display features similar to brain NSCs, including the ability to diff...

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...

Molecular signature and functional properties of human pluripotent stem cell-derived brain pericytes Brain pericytes maintain the blood-brain barrier (BBB), secrete neurotrophic factors and clear toxic proteins. Their loss in neurological disorders leads to BBB breakdown, neuronal dysfunction, and co...

Check out the preprint, we appreciate any feedback:
www.biorxiv.org/content/10.1...

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.

Functionally, iPSC-pericyte transplantation locally restored BBB integrity and promoted neuronal survival in the hippocampus of pericyte-deficient mice

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

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 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.

Then 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

Next we show iPSC-pericytes help with the formation of blood-brain barrier tight junction proteins in human brain endothelial cells.

We first compared iPSC-pericytes and primary pericytes using proteomics/phosphoproteomics and found no major differences—iPSC-PC shared 96% of proteins and 98% of phosphopeptides, including key markers, adhesion proteins, and TFs.

New preprint🚨 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 microvessels🐭

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

We also discuss few recent studies using e.g. gene and cell therapies to improve BBB integrity and neuronal function and much more!

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 → Here are a few key highlights 👇

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... 🧪 @researchhubf.bsky.social

Optimize the time window for cell therapy for #Stroke

Photothrombosis
Rag2-/-🐭
hiPSC-#NeuralProgenitorCell
intracerebral injection

7 days (vs 1 d) post injury➡️
⏫NPC proliferation
~20-fold⏫survival by 7-wk dpi👍

@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. 🧵1/7

Nice roundup on CRISPR genome editing @economist.com
www.economist.com/leaders/2025...

Regulatory T cells constrain T cells of shared specificity to enforce tolerance during infection During infections, CD4+ Foxp3+ regulatory T (Treg) cells must control autoreactive CD4+ conventional T (Tconv) cell responses against self-peptide antigens while permitting those against pathogen-deri...

#Medsky🧪 #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 that’s preventing autoimmunity.
www.science.org/doi/10.1126/...

Very cool! Thanks for sharing ☺️

@kevinbonham.com thanks Kevin! Did it myself, always happy to contribute to some work if you need similar illustrations! ☺️