Neural Stem Cell Therapeutics for Ischemic Stroke

Ischemic stroke, arising from obstruction of cerebral blood vessels, initiates a cascade of inflammation, blood–brain barrier disruption and neuronal death. Neural stem cell (NSC) therapeutics seek to counter these processes through cell replacement, trophic support and immunomodulation. Preclinical models employ a spectrum of sources, from adult neural precursor cells to induced pluripotent stem cell-derived neural progenitors, delivered intravenously, intra-arterially or intracerebrally at acute and post-acute stages. These cells can differentiate into neurons, astrocytes and oligodendrocytes, secrete neuroprotective factors, stimulate endogenous repair via neurogenesis and angiogenesis, and modulate peripheral and central immune responses. Progress hinges on optimising cell type, delivery timing, dosage and host–cell interactions, particularly in the presence of comorbidities such as hyperlipidaemia. Despite promising structural and functional recovery in animal models, challenges remain in ensuring long-term graft survival, safety and scalable manufacturing for human translation.

Research from Nature Portfolio

In a translational pig model of middle cerebral artery occlusion, transplanted induced pluripotent stem cell-derived neural stem cells demonstrated multifaceted recovery mechanisms. Multiparametric magnetic resonance imaging revealed preservation of white matter integrity, improved cerebral perfusion and metabolic activity within infarcted tissue. Therapeutic benefits correlated with reduced immune cell infiltration, enhanced neuroprotection and elevated endogenous neurogenesis. Engrafted cells differentiated into neurons and oligodendrocytes, integrating into host circuits over time. The robust recovery observed in a large-animal model underscores the clinical potential of autologous iPSC-derived grafts and informs strategies for dosing and imaging-guided evaluation in future human trials.

Neural Stem Cell Therapeutics for Ischemic Stroke publication trend

The graph below shows the total number of articles in neural stem cell therapeutics for ischemic stroke across all publications each year (not limited to Nature Index journals).

Technical terms

Neural stem cell: A self-renewing cell capable of generating the principal neural lineages—neurons, astrocytes and oligodendrocytes.

Induced pluripotent stem cell (iPSC): A differentiated somatic cell reprogrammed to a pluripotent state with the ability to form all body cell types.

Ischemic stroke: Neurological injury resulting from interrupted cerebral blood supply leading to oxygen and nutrient deprivation.

Neurogenesis: The process of generating new neurons from endogenous or transplanted neural stem or progenitor cells.

Angiogenesis: The formation of new blood vessels from existing vasculature to restore tissue perfusion.

References

1. Neural stem cell therapy for stroke: A multimechanistic approach to restoring neurological function. Brain and Behavior (2019).
2. Induced Pluripotent Stem Cell-Derived Neural Stem Cell Therapy Enhances Recovery in an Ischemic Stroke Pig Model. Scientific Reports (2017).
3. Neural precursor cell delivery induces acute post-ischemic cerebroprotection, but fails to promote long-term stroke recovery in hyperlipidemic mice due to mechanisms that include pro-inflammatory responses associated with brain hemorrhages. Journal of Neuroinflammation (2023).
4. Dying transplanted neural stem cells mediate survival bystander effects in the injured brain. Cell Death & Disease (2023).
5. Human-Induced Pluripotent Stem Cell-Derived Neural Progenitor Cells Showed Neuronal Differentiation, Neurite Extension, and Formation of Synaptic Structures in Rodent Ischemic Stroke Brains. Cells (2024).