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).
|Study Title||Phase||TSCs||Number Enrolled||Start Date||Location(s)||Status|
|Intrathecal administration of autologous mesenchymal stem cell-derived neural progenitors (MSC-NP) in progressive multiple sclerosis||Phase 2||MSCs||50||September 2018||United States||Recruiting|
|Rct comparing autologous hematopoietic stem cell transplantation versus alemtuzumab in multiple sclerosis||Phase 3||HSCs||100||March 2018||Denmark, Netherlands, Norway, (and 5 more...)||Recruiting|
|Maximizing outcome of multiple sclerosis transplantation||Phase 3||HSCs||200||November 2017||United States||Recruiting|
|Allogenic mesenchymal stem cells and physical therapy for ms treatment||Phase 1, Phase 2||MSCs||60||September 2017||Jordan||Recruiting|
|Safety study of human neural stem cells injections for secondary progressive multiple sclerosis patients||Phase 1||ASCs||24||September 2017||Italy, Switzerland||Active, not recruiting|
|Neural stem cell transplantation in multiple sclerosis patients||Phase 1||ASCs||4||May 2017||Italy||Enrolling by invitation|
|Autologous bone marrow derived stem cells for the treatment of multiple sclerosis||Phase 1||BMSCs||50||July 2016||Jordan||Active, not recruiting|
|Safety and efficacy of intravenous autologous mesenchymal stem cells for ms: A phase 2 proof of concept study||Phase 2||MSCs||40||June 2015||Canada||Recruiting|
|Reduced-intensity immunoablation and autologous hematopoietic stem cell transplantation (AHSCT) for multiple sclerosis||Phase 1||HSCs||15||May 2015||Philippines||Recruiting|
|Autologous mesenchymal stromal cells for multiple sclerosis||Phase 1, Phase 2||MSCs||8||May 2015||Spain||Active, not recruiting|
|A Study of allogeneic human UC-MSC and Liberation Therapy (When associated with CCSVI) in patients with RRMS||Phase 1, Phase 2||MSCs||69||February 2015||Trinidad and Tobago||Terminated|
|Mesenchymal stem cells for multiple sclerosis||Phase 1, Phase 2||MSCs||1||February 2015||France||Terminated|
|Optimal administration mode of autologous mesenchymal bone marrow stem cells in active and progressive multiple sclerosis||Phase 2||MSCs||36||January 2015||Occupied Palestine (Israel)||Unknown|
|Multi-center study safety of adipose derived mesenchymal stem cells for the treatment of multiple sclerosis||Phase 1||MSCs||2||November 2014||Cayman Islands||Terminated|
|Safety and efficacy of bmmnc in multiple sclerosis||Phase 1, Phase 2||BMSCs||15||June 2014||India||Unknown|
|Outcomes data of adipose stem cells to treat multiple sclerosis||Phase 1||MSCs||221||May 2014||United States||Active, not recruiting|
|Intrathecal administration of autologous mesenchymal stem cell-derived neural progenitors (MSC-NP) in patients with multiple sclerosis||Phase 1||MSCs||20||April 2014||United States||Completed|
|Assessment of bone marrow-derived cellular therapy in progressive multiple sclerosis (ACTiMuS)||Phase 2||BMSCs||80||January 2014||United Kingdom||Recruiting|
|Feasibility study of human umbilical cord tissue-derived mesenchymal stem cells in patients with multiple sclerosis||Phase 1, Phase 2||MSCs||20||January 2014||Panama||Completed|
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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