Clinical feasibility of umbilical cord tissue-derived mesenchymal stem cells in the treatment of multiple sclerosis

Abstract

Background: Multiple sclerosis (MS) is a progressively debilitating neurological condition in which the immune system abnormally erodes the myelin sheath insulating the nerves. Mesenchymal stem cells (MSC) have been used in the last decade to safely treat certain immune and inflammatory conditions.

Methods: A safety and feasibility study was completed on the use of umbilical cord MSC (UCMSC) as a treatment for MS. In this 1-year study, consenting subjects received seven intravenous infusions of 20 × 106 UCMSC over 7 days. Efficacy was assessed at baseline, 1 month and 1 year after treatment, including magnetic resonance imaging (MRI) scans, Kurtzke Expanded Disability Status Scale (EDSS), Scripps Neurological Rating Scale, Nine-Hole Peg Test, 25-Foot Walk Test, and RAND Short Form-36 quality of life questionnaire.

Results: Twenty subjects were enrolled in this study. No serious adverse events were reported. Of the mild AEs denoted as possibly related to treatment, most were headache or fatigue. Symptom improvements were most notable 1 month after treatment. Improvements were seen in EDSS scores (p < 0.03), as well as in bladder, bowel, and sexual dysfunction (p < 0.01), in non-dominant hand average scores (p < 0.01), in walk times (p < 0.02) and general perspective of a positive health change and improved quality of life. MRI scans of the brain and the cervical spinal cord showed inactive lesions in 15/18 (83.3%) subjects after 1 year.

Conclusions: Treatment with UCMSC intravenous infusions for subjects with MS is safe, and potential therapeutic benefits should be further investigated. Trial registration ClinicalTrials.gov NCT02034188. Registered Jan 13, 2014. https://ichgcp.net/clinical-trials-registry/NCT02034188.

Keywords: Mesenchymal stem cells; Multiple sclerosis; Multiple sclerosis treatment; Stem cell therapy; Umbilical cord stem cells.

Figures

Fig. 1

Kurtzke Expanded Disability Status Scale (EDSS) mean scores. Possible scores range from 0 (no disability) to 10 (death resulting from MS complications). Scores from 1.0 to 4.5 indicate an ability to walk without any aid, and scores from 5.0 to 9.5 indicate an impairment to walking. N = 20 at 1 month (same as baseline), N = 17 at 1 year. Statistically significant changes between time points are indicated with their p-values. Error bars represent standard deviations

Fig. 2

Scripps Neurological Rating Scale (SNRS) scores. Bladder, bowel and sexual dysfunction SNRS scores. The normal score is 0. A higher score on the SNRS indicates a higher level of neurological functioning, with possible scores ranging from − 10 to 100. N = 20 at 1 month (same as baseline), N = 17 at 1 year. Statistically significant changes between time points are indicated with their p-values

Fig. 3

Nine Hole Peg Test (9HPT) for non-dominant hand. Best (a) and average (b) times for non-dominant hand. The 9HPT is an evaluation of arm/upper extremity functionality or disability. A reduction in the test time from the reference time point signifies an improvement of upper extremity function. N = 20 at 1 month (same as baseline), N = 19 at 1 year. Statistically significant changes between time points are indicated with their p-values. Error bars represent standard deviations

Fig. 4

25 Foot Walk Test (25FWT) 2nd trial scores. Subjects were asked to perform two trials of a 25-Foot Walk. Not all subjects completed both trials, or performed these tests at all time points. In this figure N = 12, and statistically significant changes between time points are indicated with their p-values. Error bars represent standard deviations

Fig. 5

RAND SF-36 quality of life scores compared to baseline. Scores for the RAND SF-36 question capture health change. Scores were compared with baseline at the 1-month and 1-year visits. N = 20 at 1 month (same as baseline), N = 17 at 1 year

Fig. 6

Changes in RAND SF-36 component scores. Changes in scores for all the RAND SF-36 categories. Asterisk denotes statistically significant changes (p 

Fig. 7

Changes in magnetic resonance imaging (MRI) before and after treatment. Gadolinium-enhanced MRI scans of the brain for one subject before (a and c) and after (b and d) treatment. Lesions of interest are indicated by a white arrow. b Interval resolution of a lesion in the right frontal juxtacortical white matter (a). d Interval resolution of a lesion in the right periatrial white matter (c). Names and other personal information have been edited out of the images