Cell Therapy for Multiple Sclerosis

Abstract

The spontaneous recovery observed in the early stages of multiple sclerosis (MS) is substituted with a later progressive course and failure of endogenous processes of repair and remyelination. Although this is the basic rationale for cell therapy, it is not clear yet to what degree the MS brain is amenable for repair and whether cell therapy has an advantage in comparison to other strategies to enhance endogenous remyelination. Central to the promise of stem cell therapy is the therapeutic plasticity, by which neural precursors can replace damaged oligodendrocytes and myelin, and also effectively attenuate the autoimmune process in a local, nonsystemic manner to protect brain cells from further injury, as well as facilitate the intrinsic capacity of the brain for recovery. These fundamental immunomodulatory and neurotrophic properties are shared by stem cells of different sources. By using different routes of delivery, cells may target both affected white matter tracts and the perivascular niche where the trafficking of immune cells occur. It is unclear yet whether the therapeutic properties of transplanted cells are maintained with the duration of time. The application of neural stem cell therapy (derived from fetal brain or from human embryonic stem cells) will be realized once their purification, mass generation, and safety are guaranteed. However, previous clinical experience with bone marrow stromal (mesenchymal) stem cells and the relative easy expansion of autologous cells have opened the way to their experimental application in MS. An initial clinical trial has established the probable safety of their intravenous and intrathecal delivery. Short-term follow-up observed immunomodulatory effects and clinical benefit justifying further clinical trials.

CD133/CD140a-Based Isolation of Distinct Human Multipotent Neural Progenitor Cells and Oligodendrocyte Progenitor Cells

“…T he development of cellular therapies for myelin replacement is reliant on the preparation of myelinogenic human cells with sufficient number and purity [1]. Although various fetal human preparations can mediate extensive myelination following engraftment into shiverer/rag2 mice [2][3][4], primary fetal cells are limited by the quantity of appropriate tissue samples and/or require extensive expansion in vitro before transplantation.…”

LINGO-1-Fc-Transduced Neural Stem Cells Are Effective Therapy for Chronic Stage Experimental Autoimmune Encephalomyelitis

“…One representative of three experiments is shown and others have shown that NSCs, upon i.v. injection in EAE mice, were found in almost all peripheral organs within 10 days, were subsequently completely cleared from them by 30 days after transplantation [29,49,50] and had migrated exclusively into inflamed foci in the CNS [22,51]. Transplanted NSCs remain in the CNS for 15 months, the duration of the experiments, without causing deleterious outcomes such as tumor formation, adverse immune responses, or inappropriate anatomical accumulation [52].…”

“…Due to the limited numbers of NSCs transplanted, neural cell repopulation by exogeneous NSCs plays a relatively small part in neurological recovery, and the induction of endogeneous neurogeneration and repopulation is essential [29,51]. We and others have shown that the effects of NSCs on EAE can be significantly enhanced by engineering them to secrete various molecules such as IL-10 and NT-3 [35,50].…”

Autoimmune Disease Treatment with Stem Cell Transplantation

“…MSCs and the relatively easy expansion of autologous cells have opened the way to their experimental application in MS. Phase I clinical trials are in progress to explore the use of MSC therapy for the treatment of MS [30].…”