Mesenchymal Stem Cell Transplantation: A Novel Approach to Treating Progressive Neurological Diseases
Mesenchymal Stem Cell Transplantation: A Novel Approach to Treating Progressive Neurological Diseases
Abstract & Commentary
By Susan Gauthier, DO, MPH, Assistant Professor of Neurology and Neurosience, Weill Cornell Medical College. Dr. Gauthier reports no financial relationships relevant to the field of study.
Synopsis: In a Phase I/II open-label study of patients with multiple sclerosis and amyotrophic lateral sclerosis, mesenchymal stem cell transplantation was found to be safe and induced an early immunonologic response.
Source: Karussis D, et al. Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis. Arch Neurol 2010;67:1187-1194.
Mesenchymal stem cells (msc) are non-hematopoietic, multipotent stem-like cells that are capable of differentiating into both mesenchymal and non-mesenchymal lineages. Several studies have suggested a potential of MSC to differentiate into neurons and astrocytes.1 MSC can be relatively easily isolated and expanded from a small bone marrow aspirate; however, they have been isolated from other tissues such as adipose, umbilical cord, and teeth. MSC have the distinct advantages of genetic stability, the ability to migrate to sites of damage, and strong immunosuppressive properties. These features have been demonstrated in both autologous and heterologous transplantations.1 Thus, many studies of the use of MSC transplants in various diseases are currently ongoing in an attempt to exploit their potential therapeutic benefit. Karussis et al designed a Phase I/II study to initiate the study of MSC in two different progressive neurological disordersmultiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS).
Fifteen patients with moderate to severe MS and 19 patients with actively progressing ALS were enrolled in this early phase study. Patients' MSC were isolated from each individual's bone marrow and after clonal expansion were reintroduced via intrathecal injection and, in the majority of patients, also administered intravenously. MSC from 9 patients were labeled with superparamagnetic iron oxide ferumoxides (Feridex) for tracking cellular migration. Overall, patients tolerated the procedure well with fever (61.8%), lasting 8 to 24 hours post-injection, and headache (44.1%) being the most common adverse events. There were no serious adverse events or significant changes on MRI (immediately post injection, 1 month, and 3 to 6 months post). MSC localization, as measured by Feridex labeling, occurred in the meninges of the spinal cord, nerve roots, and the parenchyma of the spinal cord. Ventricular localization of transplanted cells was suggested by diffusion imaging in a patient with unlabeled cells. There was a clinical improvement over 6 months in the MS patients (mean EDSS of 6.7 to 5.9, P = 0.001) and clinical stability was reported in the patients with ALS. The immediate immunological effects (4 and 24 hours post-administration) of MSC transplantation were evaluated in the peripheral blood of a small subset of patients (5 with ALS, 7 with MS). There was a significant increase in CD4+CD25+ regulatory cells at 4 and 24 hours compared to baseline. Furthermore, there was a significant decrease in activated lymphocytes and antigen presenting cells (CD86+, CD83+, CD40+, and HLA-DR+ dendritic cells) at 4 and 24 hours as compared to baseline. There was no difference when the disease groups were analyzed separately.
Commentary
Given the unique features of MSC, transplantation of these cells into the central nervous system (CNS) is an attractive strategy to treat patients with progressive neurological diseases. The most appealing aspect of MSC therapy would be the potential for neurogenesis; however, the evidence for this is less convincing compared to the strong immunomodulatory effect of these cells. This study demonstrates the safety and tolerability of this novel therapeutic approach. The improvement in disability in patients with MS should be considered with caution, but notably, neither disease group worsened clinically or by MRI and an early shift to immunosuppression was appreciated. Given the potential ease and safety of using MSC for direct CNS immunomodulation, further studies in neurological diseases should be pursued. Recently, an international panel of clinicians and stem cell experts met to discuss a potential large-scale trial in MS. The consensus was that the immunodulatory effect was the most likely pathway of therapeutic benefit to patients with MS, and through the international collaboration, a Phase II clinical trial in MS has been designed.
References
1. Giordano A, et al. From the laboratory bench to the patient's bedside: An update on clinical trials with mesenchymal stem cells. J Cell Physiol 2007;211:27-35.
In a Phase I/II open-label study of patients with multiple sclerosis and amyotrophic lateral sclerosis, mesenchymal stem cell transplantation was found to be safe and induced an early immunonologic response.Subscribe Now for Access
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