Drug-like delivery methods of stem cells as biologics for stroke

ABSTRACT

Introduction: Stem cell therapy is an experimental treatment for brain disorders. Although a cellular product, stem cells can be classified as biologics based on the cells’ secretion of therapeutic substances. Treatment with stem cell biologics may appeal to stroke because of the secondary cell death mechanisms, especially neuroinflammation, that are rampant from the onset and remain elevated during the progressive phase of the disease requiring multi-pronged biological targets to effectively abrogate the neurodegenerative pathology. However, the optimal delivery methods, among other logistical approaches (i.e. cell doses and timing of intervention), for stem cell therapy will need to be refined before stem cell biologics can be successfully utilized for stroke in large scale clinical trials.

Areas covered: In this review, we discuss how the innate qualities of stem cells characterize them as biologics, how stem cell transplantation may be an ideal treatment for stroke, and the various routes of stem cell administration that have been employed in various preclinical and clinical investigations.

Expert opinion: There is a need to optimize the delivery of stem cell biologics for stroke in order to guide the safe and effective translation of this therapy from the laboratory to the clinic.

KEYWORDS:

• Stem cells
• cerebral ischemia
• drug
• inflammation
• translational research

Acknowledgement

The authors thank Ms. Sydney Corey and Ms. Brooke E. Bonsack for their excellent assistance in finalizing this manuscript.

Article Highlights

• Although long considered as a cellular product, stem cells can be classified as biologics based on the cells’ secretion of therapeutic substances

• Stem cell biologics stand as potent stroke therapeutics for sequestering secondary cell death processes

• Cell death cascades, especially aberrant neuroinflammation, plague stroke during the neurodegenerative progression of the disease

• The multifactorial progressive phase of the disease requires multi-pronged biological targets to effectively abrogate the neurodegenerative pathology

• Optimizing the transplant regimen, in particular the route of delivery, will advance the use of stem cell biologics for stroke therapy

This box summarizes key points contained in the article.

Declaration of interest

C Borlongan was funded and received royalties and stock options from Astellas, Asterias, Sanbio, Athersys, KMPHC, and International Stem Cell Corporation; and also received consultant compensation for Chiesi Farmaceutici. He also holds patents and patent applications related to stem cell biology and therapy. 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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by the National Institute of Health.