Exploratory MRI measures after intravenous autologous culture-expanded mesenchymal stem cell transplantation in multiple sclerosis

Abstract

Background Mesenchymal stem cells (MSC) have immunomodulatory and neuro-protective properties and are being studied for treatment of multiple sclerosis (MS). Tractography-based diffusion tensor imaging (DTI), cortical thickness (Cth) and T2 lesion volume (T2LV) can provide insight into treatment effects. Objective The objective of this study was to analyse the effects of MSC transplantation in MS on exploratory MRI measures. Methods MRIs were obtained from 24 MS patients from a phase 1 open-label study of autologous MSC transplantation. DTI metrics were obtained in lesions and normal-appearing white matter motor tracts (NAWM). T2LV and Cth were derived. Longitudinal evolution of MRI outcomes were modelled using linear mixed effects. Pearson’s correlation was calculated between MRI and clinical measures. Results Lesional radial diffusivity (RD) and axial diffusivity (AD) decreased pre-transplant and showed no changes post-transplant. There were mixed trends in NAWM RD and AD pre/post-transplant. Transplantation stabilized T2LV growth. NAWM RD and AD correlated with Cth, T2LV and with leg and arm function but not with cognition. Lesional DTI demonstrated similar but less robust correlations. Conclusions Microstructural tissue integrity is altered in MS. DTI changes pre-transplant may be influenced by concomitant lesion accrual. Contributor to DTI stabilization post-transplant is multifactorial. DTI of major motor tracts correlated well with clinical measures, highlighting its sensitivity to clinically meaningful changes.

Serum neurofilament light chain concentration in a phase 1/2 trial of autologous mesenchymal stem cell transplantation

“…Additional MRI metrics analyzed post-hoc included cortical thickness and further DTI parameters (FA, MD, transverse diffusivity (TD), and axial diffusivity (AD)) in lesional tissue, corticospinal tracts (reported as average of left and right), and the transcallosal motor tract. 32…”

“…Additional MRI metrics analyzed post-hoc included cortical thickness and further DTI parameters (FA, MD, transverse diffusivity (TD), and axial diffusivity (AD)) in lesional tissue, corticospinal tracts (reported as average of left and right), and the transcallosal motor tract. 32 Optical coherence tomography (OCT) was performed at each study visit using a Cirrus spectral domain machine (Carl Zeiss Meditec, Dublin, California, USA). Patients underwent two OCT scans at each visit.…”

Mesenchymal Stem Cells for Neurological Disorders

“…[ 169 ] The analyses of main outcomes in MSC treated MS patients have been proposed to explore microstructural tissue integrity using MRI. [ 170,171 ]…”

Stem Cell Therapies for Progressive Multiple Sclerosis

“…Most of these studies have employed autologous BM-MSCs or AD-MSCs (occasionally in the form of a stromal vascular fraction, AD-SVF, a heterogeneous cell fraction including MSCs, HSCs, and various myeloid and lymphoid cells, amongst others), but allogeneic MSCs from umbilical cord or placental sources have also been trialed. A number of phase 1 clinical studies have demonstrated the feasibility and safety of the IV (Cohen et al, 2018;Feng et al, 2019;Iacobaeus et al, 2019) or IT (Mohyeddin Bonab et al, 2007;Sahraian et al, 2019) administration of BM-MSCs, although in one study a large combined IT and intracisternal dose of MSCs (100 × 10 6 cells) was associated with transient encephalopathy, with seizures in one recipient (Yamout et al, 2010). In several of these pilot studies hints of therapeutic benefit were observed, but small enrolment sizes and a lack of controls preclude an assessment of efficacy.…”