Developments in intracerebral stem cell grafts

Abstract

The field of stem cell therapy has emerged as a promising research area for brain repair. Optimizing the safety and efficacy of the therapy for clinical trials will require revisiting transplantation protocols. The cell delivery route stands as a key translational item that warrants careful consideration in facilitating the success of stem cell therapy in the clinic. Intracerebral administration, compared to peripheral route, requires an invasive procedure to directly implant stem cells into injured brain. Although invasive, intracerebral transplantation circumvents the prohibitive blood brain barrier in allowing grafted cells when delivered peripherally to penetrate the brain and reach the discreet damaged brain tissues. This review will highlight milestone discoveries in cell therapy for neurological disorders, with emphasis on intracerebral transplantation in relevant animal models and provide insights necessary to optimize the safety and efficacy of cell therapy for the treatment of Parkinson’s disease, Huntington’s disease, stroke and traumatic brain injury.

Keywords:

• cell delivery
• neurodegeneration
• neurological disorders
• stem cell therapy
• translational research

Acknowledgements

The authors gratefully acknowledge the support and critical discussion offered by their colleagues at the USF Center of Aging and Brain Repair.

Financial & competing interests disclosure

CV Borlongan is supported by NIH NINDS 1R01NS071956-01, NIH NINDS 1 R21 NS089851-01, James and Esther King Foundation for Biomedical Research Program 1KG01-33966, SanBio Inc., Celgene Cellular Therapeutics, KMPHC and NeuralStem Inc. None of these funders had a role in the preparation of this manuscript. CV Borlongan holds patents and has pending patent applications in stem cell biology and therapeutic applications. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Optimization of safety and efficacy remains a key gating item in translating stem cell therapy to the clinic for treatment of neurological disorders.

• The route of administration of stem cells for a specific disease can vary; therefore, it is essential to determine which is most beneficial for the patient.

• Intracerebral route of administration stands as an efficacious way to deliver cells directly into specific brain areas.

• Understanding the disease pathology of brain disorders is critical for identifying the appropriate route of stem cell delivery.

• Characterization of the donor stem cells may provide insights into their phenotypic fate (i.e., migration potential) after transplantation and can be a factor in deciding the cell delivery route.

• In addition to optimizing the transplant regimen (i.e., cell delivery route), challenges that warrant preclinical investigations include high tissue variability, lack of scalability, ethical concerns, inability to obtain an epidemiologically meaningful quantity of tissue, graft-induced adverse effects, and the establishment of acceptable levels of efficacy and toxicity.