Stand alone or join forces? Stem cell therapy for stroke

ABSTRACT

Introduction: Stroke is a major cause of mortality and disability with a narrow therapeutic window. Stem cell therapy may enhance the stroke recovery.

Areas Covered: Regenerative medicine via stem cells stands as a novel therapy for stroke. In particular, bone marrow-derived mesenchymal stem cells (MSCs) have neuroprotective and anti-inflammatory properties that improve brain function after stroke. Here, we discuss the safety, efficacy, and mechanism of action underlying the therapeutic effects of bone marrow-derived MSCs. We also examine the discrepant transplant protocols between preclinical studies and clinical trials. Laboratory studies show the safety and efficacy of bone marrow-derived MSCs in stroke models. However, while safe, MSCs remain to be fully evaluated as effective in clinical trials. Furthermore, recognizing the multiple cell death processes associated with stroke, we next discuss the potential therapeutic benefits of a combination therapy. With preliminary results and on-going clinical trials, a careful assessment of dosing, timing, and delivery route regimens will further direct the future of stem cell therapy for neurological disorders, including stroke.

Expert Opinion: Bone marrow-derived MSCs appear to be the optimal stem cell source for stroke therapy. Optimizing dosing, timing, and delivery route should guide the clinical application of bone marrow-derived MSCs.

KEYWORDS:

• Cerebral ischemia
• regenerative medicine
• cell transplantation
• neurogenesis

Article highlights

• Stroke is a major leading cause of adult long-term disability and mortality that has limited therapeutic options.

• Regenerative medicine via stem cell therapy offers a novel strategy for the aged and diseased brain.

• Enhanced endogenous neurogenesis, neurotrophic factor secretion, cell replacement, and biobridge formation have been suggested to underlie stem cell mechanism of action.

• Autologous bone marrow-derived mesenchymal stem cell transplantation is proven to be safe, but not effective in stroke clinical trials.

• Improving the dosing, timing, and delivery route protocols is necessary for the translation of stem cell therapy to the clinical setting.

• Combination therapy, rather than stand-alone therapy, could enhance the therapeutic benefits observed from stem cell usage in a stroke model.

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Declaration of interest

CV Borlongan has patent applications related to stem cell therapy with Athersys Inc., Saneron CCEL, and SanBio Inc. 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 relationships or otherwise to disclose.

Additional information

Funding

CV Borlongan is funded by NIH NINDS R01NS071956-01, NIH NINDS R01NS090962, NIH NINDS R21NS089851-01, NIH NINDS R21094067, Veterans Affairs BX001407-01, NeuralStem, Karyopharm, SanBio Inc., International Stem Cell Corp., Saneron CCEL.