Therapeutic Stem Cells and Their Utilization in Multiple Sclerosis Clinical Trials: A Mini Review


avatar Saman Esmaeilnejad 1 , * , avatar Samaneh Dehghan ORCID 2 , avatar Mohammad Javan ORCID 1

Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran

how to cite: Esmaeilnejad S, Dehghan S, Javan M. Therapeutic Stem Cells and Their Utilization in Multiple Sclerosis Clinical Trials: A Mini Review. J Human Gen Genom. 2018;2(2):e88276. doi: 10.5812/jhgg.88276.


In the last two decades, stem cell therapy has been developed rapidly. Stem cells have now emerged as a new treatment for many major disorders including neurodegenerative diseases such multiple sclerosis (MS). Recently, the attention of researchers working on MS have been attracted to cell therapy using therapeutic stem cells (TSCs). In this brief narrative review we explore the application of TSCs in last 5 years registered clinical trials. At the end, we will discuss the challenges and hopes ahead of therapeutic stem cells in treating MS patients.

1. Therapeutic Stem Cell and Clinical Trials on Multiple Sclerosis Patients

Stem cells (SCs) are a type of cells that are capable of continuous production of new cells (1). These cells exist in embryos as well as adults, in living multicellular organisms including human beings (2). Cell therapy (CT) has long been recognized as a new method for treating various diseases (3-7). Stem cells are usually classified in a variety of ways based on their source and potential capacity (8, 9). Embryonic stem cells (ESCs), mesenchymal stem cells (MSCs), hematopoietic stem cells (HSCs), bone marrow stem cells (BMSCs), adult stem cells (ASCs) and genetically produced induced pluripotent stem cells (iPSCs) are the major types of cells that have been used in CT for various diseases (10). In this article we address these cells as therapeutic stem cells (TSCs). TSCs can be used either by direct transplantation into the patient or by using as a vehicles to transport the genes of interest as a tool for gene therapy (11). iPSCs as patient-specific models also were tested for exogenous gene delivery to the patients (12). Recently, novel genome editing tools including CRISPR has been widely used for gene therapy using TSCs (13).

Multiple sclerosis is a chronic demyelinating disease of the central nervous system, which the progressive degeneration of oligodendrocytes, followed by neural loss is its major remark (14). Many drugs have been proposed for this disease, but they all eliminate the symptoms rather than treating the disease (15). Over the past few years, Gene therapy and CT studies have been used to prevent, reverse and also treat the disease using TSCs which many of them are still in progress (16-22). There are about 58 clinical trials registered that using cells for MS treatment. Table 1 chronologically summarizes the most recent (last 5 years) trials, the type of TSCs used, their degree of progress and some additional information’s (23).

Table 1. Last 5 Years Clinical Trials Using TSCs on MS Patients (23)
Study TitlePhaseTSCsNumber EnrolledStart DateLocation(s)Status
Intrathecal administration of autologous mesenchymal stem cell-derived neural progenitors (MSC-NP) in progressive multiple sclerosisPhase 2MSCs50September 2018United StatesRecruiting
Rct comparing autologous hematopoietic stem cell transplantation versus alemtuzumab in multiple sclerosisPhase 3HSCs100March 2018Denmark, Netherlands, Norway, (and 5 more...)Recruiting
Maximizing outcome of multiple sclerosis transplantationPhase 3HSCs200November 2017United StatesRecruiting
Allogenic mesenchymal stem cells and physical therapy for ms treatmentPhase 1, Phase 2MSCs60September 2017JordanRecruiting
Safety study of human neural stem cells injections for secondary progressive multiple sclerosis patientsPhase 1ASCs24September 2017Italy, SwitzerlandActive, not recruiting
Neural stem cell transplantation in multiple sclerosis patientsPhase 1ASCs4May 2017ItalyEnrolling by invitation
Autologous bone marrow derived stem cells for the treatment of multiple sclerosisPhase 1BMSCs50July 2016JordanActive, not recruiting
Safety and efficacy of intravenous autologous mesenchymal stem cells for ms: A phase 2 proof of concept studyPhase 2MSCs40June 2015CanadaRecruiting
Reduced-intensity immunoablation and autologous hematopoietic stem cell transplantation (AHSCT) for multiple sclerosisPhase 1HSCs15May 2015PhilippinesRecruiting
Autologous mesenchymal stromal cells for multiple sclerosisPhase 1, Phase 2MSCs8May 2015SpainActive, not recruiting
A Study of allogeneic human UC-MSC and Liberation Therapy (When associated with CCSVI) in patients with RRMSPhase 1, Phase 2MSCs69February 2015Trinidad and TobagoTerminated
Mesenchymal stem cells for multiple sclerosisPhase 1, Phase 2MSCs1February 2015FranceTerminated
Optimal administration mode of autologous mesenchymal bone marrow stem cells in active and progressive multiple sclerosisPhase 2MSCs36January 2015Occupied Palestine (Israel)Unknown
Multi-center study safety of adipose derived mesenchymal stem cells for the treatment of multiple sclerosisPhase 1MSCs2November 2014Cayman IslandsTerminated
Safety and efficacy of bmmnc in multiple sclerosisPhase 1, Phase 2BMSCs15June 2014IndiaUnknown
Outcomes data of adipose stem cells to treat multiple sclerosisPhase 1MSCs221May 2014United StatesActive, not recruiting
Intrathecal administration of autologous mesenchymal stem cell-derived neural progenitors (MSC-NP) in patients with multiple sclerosisPhase 1MSCs20April 2014United StatesCompleted
Assessment of bone marrow-derived cellular therapy in progressive multiple sclerosis (ACTiMuS)Phase 2BMSCs80January 2014United KingdomRecruiting
Feasibility study of human umbilical cord tissue-derived mesenchymal stem cells in patients with multiple sclerosisPhase 1, Phase 2MSCs20January 2014PanamaCompleted

2. The Hopes and Challenges Ahead of TSCs to Treat Neurodegenerative Diseases

TSC therapy has not reached its full potential and maturity, yet. Research in this area is still faced with several discrete challenges. The difficulty in the precise and accurate transplantation in distributed sites of lesions, predicting the precise number of the stem cells for effective transplantation without unexpected side effects to ensure the highest efficiency, accurate timing and choosing the best transplantation approach are among the most important challenges that need to be addressed (24). Other problems that we are likely to encounter after successful transplantation are: Probability of producing cancerous masses, epilepsy and immunity (25). Despite all these challenges, the scientific and clinical community are committed to advancing this therapeutic approach. They believe that this therapeutic approach will have a beneficial and major role in the future treatments of this disease.


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