Treatment of Neurodegenerative Diseases with Stem Cells: Key Features
Neurodegenerative diseases (such as Parkinson’s disease, Alzheimer’s, ALS, multiple sclerosis) are associated with the gradual loss of specific types of neurons or glial cells. Stem cell (SC) therapy offers fundamentally new possibilities here — but with many particular features.
Which Types of Stem Cells Are Used?
✅ Mesenchymal (MSC) — from bone marrow, adipose tissue, umbilical cord
✅ Neural (NSC) — specialized neural progenitors
✅ Induced pluripotent stem cells (iPSC) — reprogrammed patient’s own cells
✅ Embryonic stem cells (ESC) — and precursor cells from neural tissue (neurospheres, axons, neuroblasts)
✅ Fetal stem cells (FSC) — of neural origin
Main Mechanisms of Action
1️⃣ Neuroprotection → secretion of growth factors, anti-inflammatory molecules, reduction of neuronal death
2️⃣ Immunomodulation → reduction of inflammation, especially in multiple sclerosis
3️⃣ Regeneration → replacement of lost neurons
4️⃣ Activation of local stem cell niches → stimulating the patient’s own cells to recover
What Can We Really Expect?
| What is promised? | What is realistic? |
|---|---|
| Complete restoration | Improved motor skills, memory, slowed progression |
| Replacement of lost neurons | Support for surviving cells, regeneration of new ones in organelles method |
| Single infusion → cure | Courses of infusions, maintenance therapy |
New Nanotechnologies Already Used in Our Clinic!
• Exosomes from stem cells (no cells, only signaling molecules)
• Genetic modification of MSC and NSC to enhance effects
• Mitochondria — intracellular structures for cellular energy exchange
• 3D organoids for replacing damaged brain regions
• Organelles (neurotrophins) capable of easily crossing the BBB
MSC (Mesenchymal Stem Cells)
• Prospects:
👉 tissue regeneration, immunomodulation (e.g., in autoimmune diseases)
👉 already used in clinical trials and some therapies today
NSC (Neural Stem Cells)
• Source: embryonic or fetal tissues, also derived from iPSC
• Prospects:
👉 treatment of neurological diseases (Parkinson’s, Alzheimer’s, dementia, spinal cord injuries)
👉 highly specialized but limited in universality
iPSC (Induced Pluripotent Stem Cells)
• Source: reprogrammed somatic cells (usually skin, blood)
• Prospects:
👉 powerful tool for disease modeling, personalized medicine
👉 source of cells for regenerating any tissue
Why Is It Important That Stem Cells Cross the BBB (Blood-Brain Barrier)?
The BBB is a very tight barrier between the blood and brain tissue. It protects the brain from toxins, pathogens, and excess molecules but simultaneously hinders the delivery of drugs and cells.
When treating neurodegenerative diseases (Alzheimer’s, Parkinson’s, multiple sclerosis, ALS, etc.), the goal of cell therapy is:
✅ to replace lost neurons,
✅ restore damaged neural networks,
✅ modulate inflammation in the CNS,
✅ support surrounding cells (for example, via neurotrophic factors).
But for these effects to materialize, the stem cells (such as NSC or iPSC-derived neurons):
👉 must reach the brain or spinal cord directly,
👉 and interact with neurons and glial cells.
If simple cells (like mesenchymal cells from any material) are just infused into the bloodstream, the BBB won’t let them through — it’s designed so that large molecules, let alone cells, cannot cross.
What Happens If We Ignore the BBB?
• Stem cells will remain in peripheral blood, liver, spleen.
• They will not exert direct effects in the CNS.
• False expectations of effect or waste of resources may result.
• Sometimes, part of the effect may come from systemic immunomodulatory actions, but this is no substitute for direct cellular repair in the brain.
What methods we use to cross the BBB in Practice?
✅ Intracranial or intrathecal injections — deliver cells directly into the brain or cerebrospinal fluid.
✅ Genetic modification of cells or nanoparticles — to allow them to cross the barrier themselves.
✅ Selection of cell types or organelles capable of migrating across the BBB — but importantly, using carrier cells.
Full Stem Cells (Functional) Almost Never Cross the BBB . It’s too dense.
But there are exceptions and bypass strategies, which we use in medical practice to treat neurodegenerative diseases.
Overview of Cells and Vesicles by Ability to Cross the BBB
| Item | How It Crosses the BBB | Notes |
|---|---|---|
| Mesenchymal stem cells (MSC) | Usually — no. But… they can act through released vesicles (exosomes), which do cross. | MSCs are often used not for direct “entry” but for systemic immunomodulatory effects. |
| Neural stem cells (NSC) | No, they don’t cross on their own. They are delivered intracranially or intrathecally. | Considered promising but require local delivery. |
| iPSC-derived neurons | No, they don’t cross on their own. | Require transplantation directly into the CNS. |
| Exosomes (extracellular vesicles) from MSC or NSC | Yes! These nanoparticles (30–150 nm) can cross the BBB. | One of the hottest trends — using not the cells but their exosomes. They carry proteins, mRNA, miRNA, signaling molecules. |
| Microglia / macrophages | During inflammation, they can migrate across the BBB. | Research is ongoing on “loading” them with therapeutic agents. |
| Mitochondria or neurotrophins (organelles) | On their own — no. But they can be delivered via exosomes or nanocarriers. | Targeted delivery of mitochondria for neurodegeneration treatment is the most innovative and effective method. |
What’s Truly Promising and Proven by Treatment Protocols?
✅ MSC/NSC exosomes combined with organelles — currently the top candidate because:
• they easily penetrate the BBB,
• they don’t cause immune reactions,
• they can be “loaded” with genes, proteins,
• they pose no risk compared to using whole stem cells.
✅ Engineered nanoparticles — also introduced to deliver genes, organelles, and other extracellular structures.
Final Notes
When it comes specifically to the BBB, it’s not the cells themselves but their derivatives — exosomes and microvesicles combined with differentiated organelles — that work best, enabling rapid and high-quality repair of damaged brain areas.
In our practice, we use all the above-described types of stem cell therapies because, in many cases, combined methods and biocultures are needed, which can also help restore already lost functions — not just achieve a halt in the degenerative process.