Ruslan Rust

“Time is brain” for cell therapies?🧠

Our #AdvSci perspective😆
@rrust.bsky.social
@dominikusbrian.com
@lydenlab.bsky.social

#StemCellTherapy for #Stroke should be timed to a biomarker-defined “window of receptivity”, not just the thrombolysis clock

advanced.onlinelibrary.wiley.com/doi/10.1002/...

Lymphoid gene expression supports neuroprotective microglia function - Nature PU.1low CD28-expressing microglia may act as suppressive cells in Alzheimer’s disease, mitigating its progression by reducing neuroinflammation and amyloid plaque load, indicating potential immunother...

www.nature.com/articles/s41...

New in @natureportfolio.nature.com on microglial regulation in Alzheimer’s disease. The study shows that microglia with low PU.1 expression and surface CD28 reduce amyloid pathology and inflammation. It highlights immune co-stimulatory pathways as potential targets in AD. Very interesting!

Molecular profiling of brain endothelial cell to astrocyte endfoot communication in mouse and human - Nature Communications Deciphering body-brain communication pathways is key to a deeper understanding of brain physiology and pathology. Here, the authors define the astrocyte endfoot proteome and show dynamic vascular-to-a...

www.nature.com/articles/s41...

Great work 👏 mapping how brain endothelial cells communicate with astrocyte endfeet at the blood–brain barrier in @natureportfolio.nature.com

The study identifies ligand–receptor pairs conserved in humans and altered in MS and Alzheimer’s.

Makes me also wonder how many could be druggable targets.

Thiorphan reprograms neurons to promote functional recovery after spinal cord injury - Nature Thiorphan is identified as a new and effective drug treatment for spinal cord injury that can be adopted across nervous system disease states in the development of new therapies for human neurological...

Link: www.nature.com/articles/s41...

Interesting new work @natureportfolio.nature.com showing that a small molecule identified through in silico transcriptome matching (thiorphan) enhances corticospinal regeneration after spinal cord injury. Combined with neural stem cell grafts, it improved forelimb recovery and axonal growth.

Generation of human nucleus basalis organoids with functional nbM-cortical cholinergic projections in transplanted assembloids The nucleus basalis of Meynert (nbM) regulates cortical function and cognition. Liu and colleagues report a method for creating human nbM organoids (hnbMOs) containing cholinergic projection neurons t...

Link: www.cell.com/cell-stem-ce...

Interesting new work modeling human cholinergic circuitry! Researchers generated nbM organoids from hPSCs and fused them with cortical organoids to form functional nbM–cortical assembloids. This provides a platform to study deficits seen in Down syndrome. @cp-cellstemcell.bsky.social

The brain neurovascular epigenome and its association with dementia Ziegler et al. reveal distinct genetic and epigenetic mechanisms underlying Alzheimer’s disease and cerebral small vessel disease within neurovascular cells, identifying immune-related AD risk and bro...

www.cell.com/neuron/fullt...

The brain neurovascular epigenome and its association with dementia @cp-neuron.bsky.social

Great study that maps cell-type-specific regulomes showing that small vessel disease heritability spans the neurovascular unit, incl astrocytes.

These findings link vascular risk and Alzheimer’s mechanisms.

Pluripotent Cells Expressing APOE4 Exhibit a Pronounced Pro-Apoptotic Phenotype Accompanied by Markers of Hyperinflammation and a Blunted NF-κB Response

www.mdpi.com/1422-0067/26...

Important study shows that a new 3D method can efficiently produce dopamine neuron precursors from stem cells. The researchers also tracked how these cells grow and connect after transplantation, big step for Parkinson’s disease treatment!
cell.com/cell-stem-ce...

Great study dissecting molecular hallmarks of neuronal resilience in Alzheimer’s disease highlighting natural protective mechanisms that could help preserve cognition.

x.com/rust_ruslan/...

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.