How does one inject cell therapies/jean hebert's tissue deep into the midbrain without damaging the tissue in between

#1

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[especially impt for parkinson’s]

I think one person said "you could replace the brain one column at a time, then have the brain gradually adjust (the brain is remarkably adaptable after local injuries), then remove another column, then do it again. But there’s surgical/logistic risk from doing this too many times.

(it might not work that way bc the horizontal connections still matter). it might be ok for the brain to lose some memory in the process of renewing itself (as long as you maintain continuity of consciousness)

I think someone mentioned deciduous and another mentioned clearpoint

eg

#2

(I wish I took better notes at the edge esmeralda neurotech thing, agh, I didn’t take notes via chatgpt as much as I should have)

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You don’t do this by having cells “travel through” the brain. You do it by putting a very thin delivery cannula directly into the target using stereotactic navigation. The “in between” brain is not untouched, because biology refuses to be neat, but the injury is reduced to a narrow planned track. Tiny surgical vandalism, basically, but with maps. :brain::nut_and_bolt:

For the Parkinson’s/iPSC dopaminergic graft diagram, the real-world version is roughly:

  1. Pre-op imaging maps the route
    MRI, sometimes CT/vascular imaging, is used to plan a trajectory that avoids obvious blood vessels, sulci, ventricles, and functionally important tissue.

  2. Stereotactic navigation locks the coordinates
    Either a frame-based stereotactic system or frameless MRI-guided system is used. In the 2025 Nature bemdaneprocel trial, cells were delivered bilaterally into the post-commissural putamen, using either intraoperative MRI-guided frameless delivery or a frame-based stereotactic approach. (Nature)

  3. A burr hole is made, then a cannula goes through a planned path
    The cannula is narrow. It still displaces and injures tissue along its track, but far less than open surgery would. In the bemdaneprocel trial, they used a modified cannula and made multiple small deposits in each putamen rather than dumping cells in one blob like a deranged pastry chef. (Nature)

  4. Cells are deposited locally
    Dopaminergic progenitors are placed where dopamine input is needed, especially the putamen. They are not expected to wander through the brain to find their destiny like underpaid interns. They survive, mature, extend processes, release dopamine, and integrate locally over time.

  5. Post-op monitoring catches trouble
    MRI follow-up looks for hemorrhage, inflammation, graft overgrowth, tumor formation, edema, or misplacement. Immunosuppression is often used for allogeneic products, because the immune system also enjoys ruining ambitious biomedical projects. BlueRock’s phase 1 bemdaneprocel work used a one-year immunosuppression regimen. (BlueRock Therapeutics LP)

The key point: there is always some track damage, but neurosurgeons try to make it tiny, predictable, and outside critical structures. The trade is: accept a controlled needle/cannula path to reach a deep target that is already part of a severe disease circuit.

On Savanna Biotherapeutics: yes, if by “SMG” you mean their iPSC-derived microglia graft/replacement concept, it is similar in surgical genre but not similar in biological mission. Savanna says its SB-101 program is an iPSC-derived microglia therapy for ALSP, a CSF1R-mutation leukoencephalopathy, delivered by a one-time MRI-guided stereotactic procedure, with microglia intended to engraft, self-renew, and migrate throughout the brain. (BIO International Convention 2026)

So the comparison is:

Feature Parkinson’s dopaminergic graft Savanna SB-101 microglia approach
Cell type Dopaminergic neuron progenitors iPSC-derived microglia
Disease target Parkinson’s disease ALSP / CSF1R-related disease
Main target logic Replace lost dopamine input in putamen Replace dysfunctional brain immune cells
Desired spread Mostly local striatal integration CNS-wide microglial engraftment/migration
Delivery style Stereotactic brain delivery Publicly described as MRI-guided stereotactic delivery

The weird but important difference: dopamine neurons are site-specific wiring therapy, while microglia are migratory resident immune-cell therapy. Dopaminergic cells need to be placed where the dopamine deficit matters. Microglia can, in principle, spread through brain tissue and occupy ecological niches, which is why microglia therapy looks more like “replace the maintenance staff across the whole building” rather than “repair one broken circuit.” Recent iPSC-microglia work supports the idea that engineered iPSC-microglia can engraft and provide broader CNS delivery functions, at least experimentally. (ScienceDirect)

So: yes, Savanna is doing something procedurally adjacent, meaning stereotactic iPSC-derived cell delivery into the CNS. But it is not just Parkinson’s putamen transplantation with a different label. It is more ambitious in distribution, and therefore has a different safety problem: not just “can we place cells without wrecking the path,” but “can we control engraftment, migration, immune behavior, persistence, and long-term phenotype across the brain.” Humanity looked at the immune system inside the skull and said, “what if we swapped parts,” because apparently normal medicine was too relaxing.

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