Cell Therapy for Brain Regeneration

Research focus

Patients suffering from brain injuries have limited therapeutic options and are often left with considerable disabilities. To promote recovery, cell therapies are an emerging new treatment paradigm and are considered as a potential regenerative strategy for patients with remaining neurologic deficits. Before cell therapies can become clinically viable, a number of uncertainties still need to be resolved in preclinical research regarding e.g., the cell source, delivery route, and graft-host immunocompatibility.

Our research focuses on overcoming these limitations using state-of-the-art genetic, molecular, and computational tools. We have recently generated a scalable neural cell source from induced pluripotent stem cells (iPSCs) under xeno-free conditions that can be continuously tracked in vivo in collaboration with Dr. Christian Tackenberg. These cells will be genetically engineered with a brain-shuttle system to facilitate systemic delivery across the brain barriers. To circumvent immune rejection, transplants will co-express distinct immunosuppressive molecules together with safety checkpoints. Efficacy of these advanced cell therapies will be evaluated through an experimental pipeline comprising i.a. in vivo imaging, deep learning-based behavioral profiling, and spatially resolved transcriptomics. The generated findings will be valuable to advance cell therapy for brain injury further towards clinical applications in the foreseeable future.

Funding

Swiss National Science Foundation (Spark), 3R Competence Center

 

Illustrative Figure

Experimental overview of cell therapies after brain injury
Experimental overview of cell therapies after brain injury
(A) Ischemic stroke is performed using the photothrombotic stroke model. (B) Successful induction of a stroke is confirmed with laser doppler imaging (C, D) Stroke size analysis reveals location and volume of infarct region. (E) Bioluminescent and fluorescent reporter facilitates longitudinal detection of transplanted cells in vivo and detection within histology sections. (F, G) Gait abnormalities and functional deficits are identified using deep learning-based behavior tracking.