Immune Mechanisms Underlying the Beneficial Effects of Autologous Hematopoietic Stem Cell Transplantation in Multiple Sclerosis

Gosselin, David; Rivest, Serge

doi:10.1007/s13311-011-0062-0

Cited by 18 publications

(13 citation statements)

References 44 publications

(55 reference statements)

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“…Autologous hematopoietic stem cell transplantation, a radical approach to target the immune system, has shown great benefits in humans (Burt et al, 2009). The beneficial effects of such a strategy depend on the formation of a novel tolerant immune system and/or the long-lasting depletion of immunoreactive T cells (Gosselin and Rivest, 2011) (Figure 5).…”

Section: Multiple Sclerosismentioning

confidence: 99%

Innate Immunity in the CNS: Redefining the Relationship between the CNS and Its Environment

Lampron

ElAli

Rivest

2013

Neuron

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240

205

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The concept of the CNS as an immune-privileged organ has led to a common misunderstanding that it is not an active immunological organ, guarded from its surroundings by the blood-brain barrier (BBB). Recent advances in this field clearly demonstrate that the CNS is a highly immunologically active organ, with complex immune responses mostly based on innate immune processes. Such responses implicate a continuum of heterogeneous cell types both inside the CNS, in the periphery, and at their interface, the BBB. This Review aims to discuss the importance of the BBB as the first line of defense against brain infections and injuries of the CNS and the main molecular mechanisms involved in the control of the innate immune system of the CNS. We also review the central role of the neurovascular unit in diseases of the CNS and how it can be targeted for novel therapeutic strategies.

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Section: Multiple Sclerosismentioning

confidence: 99%

Innate Immunity in the CNS: Redefining the Relationship between the CNS and Its Environment

Lampron

ElAli

Rivest

2013

Neuron

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240

205

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“…Many immunomodulatory treatments are effective for the relapsing-remitting form of the disease by alleviating the Th1/Th17-mediated autoimmune response against myelin [146][147][148][149]. Currently, HSC transplantation is regarded as a very promising therapeutic avenue, probably due to both the immune reset and the state of immunodeficiency conferred by the HSCT and the lymphoablative conditioning, respectively [16]. While T cells are clearly the number one culprit for the pathogenesis of EAE and MS, the involvement of infiltrating monocytic cells and macrophages cannot be overlooked, as they strongly influence the clinical outcome.…”

Section: Multiple Sclerosis and Demyelinating Diseasesmentioning

confidence: 99%

“…In humans, peroxisomal disorders [11], lysosomal storage diseases (LSD) [12] and autoimmune disorders [13][14][15], including multiple sclerosis (MS) [16,17], have been successfully treated by way of bone marrow or hematopoietic stem cell (HSC) transplantation. Besides such therapeutic feats, BMT has also permitted considerable breakthroughs in fundamental research by empowering scientists to perform tracking, fate mapping and functional studies with various (transgenic) chimeric mouse models.…”

Section: Introductionmentioning

confidence: 99%

Bone marrow-derived macrophages and the CNS: An update on the use of experimental chimeric mouse models and bone marrow transplantation in neurological disorders

Larochelle

Bellavance

Michaud

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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The central nervous system (CNS) is a very unique system with multiple features that differentiate it from systemic tissues. One of the most captivating aspects of its distinctive nature is the presence of the blood brain barrier (BBB), which seals it from the periphery. Therefore, to preserve tissue homeostasis, the CNS has to rely heavily on resident cells such as microglia. These pivotal cells of the mononuclear lineage have important and dichotomous roles according to various neurological disorders. However, certain insults can overwhelm microglia as well as compromising the integrity of the BBB, thus allowing the infiltration of bone marrow-derived macrophages (BMDMs). The use of myeloablation and bone marrow transplantation allowed the generation of chimeric mice to study resident microglia and infiltrated BMDM separately. This breakthrough completely revolutionized the way we captured these 2 types of mononuclear phagocytic cells. We now realize that microglia and BMDM exhibit distinct features and appear to perform different tasks. Since these cells are central in several pathologies, it is crucial to use chimeric mice to analyze their functions and mechanisms to possibly harness them for therapeutic purpose. This review will shed light on the advent of this methodology and how it allowed deciphering the ontology of microglia and its maintenance during adulthood. We will also compare the different strategies used to perform myeloablation. Finally, we will discuss the landmark studies that used chimeric mice to characterize the roles of microglia and BMDM in several neurological disorders. This article is part of a Special Issue entitled: Neuro Inflammation edited by Helga E. de Vries and Markus Schwaninger.

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“…Autologous HSC transplantation to MS patients was shown to be safe and to reverse neurological deficits [109]. However, it remains unclear whether these beneficial effects are the result of the newly reconstituted immune system or of the lymphoablative conditioning regimen-induced immune suppression performed in the study [110].…”

Section: Multiple Sclerosismentioning

confidence: 99%

Cell-Based Therapy Approaches: The Hope for Incurable Diseases

Buzhor¹,

Leshansky²,

Blumenthal³

et al. 2014

Regen. Med.

145

105

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Cell therapies aim to repair the mechanisms underlying disease initiation and progression, achieved through trophic effect or by cell replacement. Multiple cell types can be utilized in such therapies, including stem, progenitor or primary cells. This review covers the current state of cell therapies designed for the prominent disorders, including cardiovascular, neurological (Parkinson's disease, amyotrophic lateral sclerosis, stroke, spinal cord injury), autoimmune (Type 1 diabetes, multiple sclerosis, Crohn's disease), ophthalmologic, renal, liver and skeletal (osteoarthritis) diseases. Various cell therapies have reached advanced clinical trial phases with potential marketing approvals in the near future, many of which are based on mesenchymal stem cells. Advances in pluripotent stem cell research hold great promise for regenerative medicine. The information presented in this review is based on the analysis of the cell therapy collection detailed in LifeMap Discovery(®) (LifeMap Sciences Inc., USA) the database of embryonic development, stem cell research and regenerative medicine.

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Immune Mechanisms Underlying the Beneficial Effects of Autologous Hematopoietic Stem Cell Transplantation in Multiple Sclerosis

Cited by 18 publications

References 44 publications

Innate Immunity in the CNS: Redefining the Relationship between the CNS and Its Environment

Innate Immunity in the CNS: Redefining the Relationship between the CNS and Its Environment

Bone marrow-derived macrophages and the CNS: An update on the use of experimental chimeric mouse models and bone marrow transplantation in neurological disorders

Cell-Based Therapy Approaches: The Hope for Incurable Diseases

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