Stem Cell-based Therapies in Multiple Sclerosis

Kimiskidis Vk

doi:10.4172/2157-7412.s3-006

Abstract

The method of intensive immunosuppressive therapy followed by autologous hematopoietic stem cell transplantation (HSCT) has been used in the last eighteen years for the management of severe forms of Multiple Sclerosis (MS) and has been claimed to yield superior results. However, it is still not an established method of MS treatment, because it has not demonstrated its superior efficacy in comparative trials, owing to methodological difficulties and lack of sufficient patient recruitment. The main criticism has been the transplant-associated toxicity and an approximately 3% risk of mortality. Based on the results of these studies, HSCT has a sustained effect in suppressing disease progression for long periods of time, while it may also bring about sustained clinical improvement, especially if patients are in the relapsing-remitting phase or have active Magnetic Resonance Imaging (MRI) lesions. Three particular points merit to be stressed: (a) the nearly 100% eradication of active Central Nervous System (CNS) lesions on MRI, sustained over time; (b) the dramatic effect on the so-called “malignant” MS forms; (c) the qualitative immunological changes post-HSCT resulting in reconstitution of the clonal diversity and in regeneration of regulatory cells. Whether the latter changes, can also result in immune tolerance is yet to be definitely shown. An alternative approach to HSCT involves the transplantation of Mesenchymal stem cells (MSCs). This interesting approach has been explored in a limited number of phase I/II studies with promising results that await confirmation in the context of larger scale, controlled trials. In conclusion, HSCT is not a therapy for the general population of MS patients; it is a powerful therapy with long-term benefits that need to be weighed against certain toxicity risks; and in critical situations, like the very aggressive, rapidly progressing and refractory “malignant” form, it may have a life-saving effect with a meaningful and long-lasting improvement of disability.

Highlights

During the last two decades, accumulating experimental and clinical evidence suggested that hemopoietic stem cell transplantation (HSCT) might be used for the treatment of aggressive Multiple Sclerosis (MS), unresponsive to conventional immunomodulatory and immunosuppressive agents
There is emerging evidence that other types of stem cells, including mesenchymal (MSC) and neural cell precursors, olfactory ensheathing cells, oligodendrocyte progenitors and embryonic stem cells, might be used in Central Nervous System (CNS) demyelinative diseases with beneficial effects. These stem cell-based therapies have received much attention, both in the scientific and lay press, and those that have reached the stage of clinical trials (i.e. HSCT & Mesenchymal stem cells (MSCs) transplantation) will be briefly discussed in the following report
Immunosuppressive agents act in a dose-dependent manner, and high doses can be more effective, but they are associated with morbidity risks

Summary

Introduction

During the last two decades, accumulating experimental and clinical evidence suggested that hemopoietic stem cell transplantation (HSCT) might be used for the treatment of aggressive Multiple Sclerosis (MS), unresponsive to conventional immunomodulatory and immunosuppressive agents. These stem cell-based therapies have received much attention, both in the scientific and lay press, and those that have reached the stage of clinical trials (i.e. HSCT & MSC transplantation) will be briefly discussed in the following report.

Results

Conclusion