Cell Therapy for Chronic Stroke

Lawrence R. Wechsler, MD; Damien Bates, MD, PhD; Paul Stroemer, PhD; Yaisa S. Andrews-Zwilling, PhD; Irina Aizman, PhD

Disclosures

Stroke. 2018;49(5):1066-1074. 

In This Article

Abstract and Introduction

Introduction

Recent advances in stroke treatment have targeted acute and subacute stroke with therapies administered in the first 48 hours after onset. Current treatment options focus on dissolution of thrombus via the use of a tissue-type plasminogen activator within 4.5 hours (eg, alteplase), or mechanical thrombectomy within 6 hours of stroke onset.[1–3] However, both of these approaches are applicable to limited numbers of stroke patients and not all patients achieve good outcomes.[4]

Although the pathology of acute stroke is well described, the time course for recovery is not. Most return of function after stroke occurs early and evidence suggests that recovery plateaus 3 to 6 months after stroke onset.[5] For the purposes of this article, chronic stroke will be defined as 6 months to years after onset. At this point, liquefaction of damaged tissue should be complete resulting in a fluid-filled cyst. Behavioral recovery tends to plateau during this period revealing the likely scale of permanent disability.[6,7]

In the United States, 795 000 people experience a new or recurrent stroke each year, with the prevalence of stroke estimated to be 7.2 million cases during 2014 in patients >20 years of age.[8]

Current therapeutic approaches have not yielded significant benefits for patients with chronic stroke. Incorporation of physical therapy programs to help augment recovery in motor function in the days to weeks after stroke may be of limited use.[9] Transcranial magnetic stimulation has been investigated, however, there is no definitive evidence of efficacy with this approach.[10,11] Administration of catecholamine agonists (eg, amphetamine) or ion channel mediators (dalfampridine) have not been reported to be effective.[12–15] Enhancing the generation of endogenous stem cells via the administration of granulocyte colony-stimulating factor has not been successful in improving outcomes.[16] Studies investigating the efficacy of fluoxetine administration to patients weeks to 6 months poststroke are ongoing.[17,18]

To date, human studies of cell therapies for chronic stroke have demonstrated adequate safety, and efficacy suggestive of a beneficial effect in a group of patients with plateaued endogenous recovery. The potential mechanisms of action of various cell types, their routes of administration, and evidence for safety and efficacy are discussed in detail below.

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