Probable Factors Associated with Response to Mesenchymal Stem Cell Therapy in Stroke Patients: A Post Hoc Analysis of the STARTING-2 Trial.

Won Hyuk Chang,Jungsoo Lee,Oh Young Bang,Yun-Hee Kim,Jong-Won Chung

doi:10.3390/jpm11111137

Abstract

The aim of this study was to identify factors associated with improved motor function of the lower extremities in response to mesenchymal stem cell (MSC) therapy in patients with ischemic stroke. This study was a post hoc analysis of data from a prospective, open-label, randomized controlled trial of MSC therapy for patients with ischemic stroke patients associated with severe middle cerebral artery territory (STARTING-2 trial). Lower limb motor function was scored based on the lower limb of Fugl–Meyer assessment (FMA-LL) score before MSC therapy and at 3 months after stroke. All FMA-LL changes greater than or equal to six points were considered clinically significant. Univariate and multivariate binary logistic regression models were used to determine possible predictors of clinically significant lower limb motor response to MSC therapy. Twelve (33%) of the thirty-six patients receiving MSC therapy reached a minimal clinically important difference (MCID) of FMA-LL. The two independent factors with the greatest impact on response to MSC therapy for achieving an MCID in FMA-LL score were: (1) the time from stroke onset to MSC therapy, and (2) age (p < 0.05). In addition, obese stroke patients responded better to MSC therapy than stroke patients with normal weight. In conclusion, this post hoc analysis might suggest the need for recruiting stroke patients at younger and early after stroke onset in future clinical trials of MSC therapy for stroke.

Highlights

Many stroke survivors continue to suffer from significant motor impairments [1].Ambulation is an essential part of disability in stroke patients
We have previously reported the results of the STARTING (STem cell Application Researches and Trials In NeuroloGy) trial, a randomized controlled trial of intravenous application of autologous mesenchymal stem cells (MSCs), cultureexpanded with fetal bovine serum (FBS), in the subacute phase of stroke [6]
There was a relatively large standard deviation in the change of lower limb score of the Fugl–Meyer assessment (FMA-LL) that was measured as the lower extremity motor function in patients with stroke suggesting a highly variable response to MSC therapy

Summary

Introduction

Many stroke survivors continue to suffer from significant motor impairments [1].Ambulation is an essential part of disability in stroke patients. Impairment of lower extremity motor has been known as one of the major contributors to ambulatory disability after stroke [1,3]. Most post-stroke care in the subacute phase depends on rehabilitation interventions, the improvement in lower extremity motor function, especially in patients with severe ischemic stroke, is still a challenge [4]. The STARTING-2 trial showed that MSC therapy improved lower extremity motor function in patients with subacute stroke with no significant adverse effects [7]. There was a relatively large standard deviation in the change of lower limb score of the Fugl–Meyer assessment (FMA-LL) that was measured as the lower extremity motor function in patients with stroke suggesting a highly variable response to MSC therapy. Multiple interacting factors are likely to affect motor recovery in stroke patients [8]; little is known about the factors that predict the efficacy of MSC therapy

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