The mesenchymal stem cells in multiple sclerosis (MSCIMS) trial protocol and baseline cohort characteristics: an open-label pre-test: post-test study with blinded outcome assessments

Abstract

BackgroundNo treatments are currently available that slow, stop, or reverse disease progression in established multiple sclerosis (MS). The Mesenchymal Stem Cells in Multiple Sclerosis (MSCIMS) trial tests the safety and feasibility of treatment with a candidate cell-based therapy, and will inform the wider challenge of designing early phase clinical trials to evaluate putative neuroprotective therapies in progressive MS. Illustrated by the MSCIMS trial protocol, we describe a novel methodology based on detailed assessment of the anterior visual pathway as a model of wider disease processes - the "sentinel lesion approach".Methods/designMSCIMS is a phase IIA study of autologous mesenchymal stem cells (MSCs) in secondary progressive MS. A pre-test : post-test design is used with healthy controls providing normative data for inter-session variability. Complementary eligibility criteria and outcomes are used to select participants with disease affecting the anterior visual pathway.ResultsTen participants with MS and eight healthy controls were recruited between October 2008 and March 2009. Mesenchymal stem cells were successfully isolated, expanded and characterised in vitro for all participants in the treatment arm.ConclusionsIn addition to determining the safety and feasibility of the intervention and informing design of future studies to address efficacy, MSCIMS adopts a novel strategy for testing neuroprotective agents in MS - the sentinel lesion approach - serving as proof of principle for its future wider applicability.Trial registrationClinicalTrials.gov (NCT00395200).

Efficient manufacturing of therapeutic mesenchymal stromal cells with the use of the Quantum Cell Expansion System

“…Other groups have reported the successful generation of large numbers of MSCs (>1×10 9 cells after 3-4 passages) by utilizing up to 8, 10-stack cell factories concurrently. (13, 14) Although our experience with this approach is limited, it uses fewer consumables than the flask-based approach and has fewer open events, though the labor required is still considerable.…”

“…Use of hundreds of cell culture flasks to generate the required numbers of cells is extremely laborious, and involves thousands of open events, which increase the possibility of contamination. While cell factories overcome some of these issues,(13, 14) they can be technically challenging, even for experienced users. (15) For example, visualizing cells is difficult due to the multiple layers, and in our experience, a good cell recovery is challenging when using these devices with MSCs.…”

Recent achievements in stem cell-mediated myelin repair

“…These observations clearly emphasize the need for further investigations. An overview of multiple sclerosis-related clinical trials with MSCs is provided in Table 1 [81][82][83][84][85][86][87][88].…”

Reverse engineering human neurodegenerative disease using pluripotent stem cell technology

“…MSCs and NSCs have been used to generate immunomodulatory cells, growth factor-releasing cells, functional support cells such as glia, or GABAergic interneurons to modify MN survival and activity. Several clinical studies (Choi et al, 2010; Connick et al, 2011; Karussis et al, 2010; Mazzini et al, 2012; Xiao et al, 2015) have examined the effect of transplanting MSCs to alter the inflammatory microenvironment in the spinal cord of ALS patients. Intravenous allo-transplantation of MSCs showed migration of the cells to the pathologic lesions.…”