The Influence of Xenotransplant Immunogenicity and Immunosuppression on Host MHC Expression in the Rat CNS

Czech, Kimberly A.; Ryan, Jason; Sagen, Jacqueline; Pappas, George D.

doi:10.1006/exnr.1997.6589

Cited by 40 publications

(17 citation statements)

References 27 publications

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“…Third, leukocyte recruitment into the CNS appears to successfully resolve some CNS viral infections, such as Sindbis virus encephalitis, without the development of any apparent long-term bystander effects (Griffin et al, 1997). Fourth, based on the relatively prolonged survival of xenografts (tissue grafts from different species) in immunosuppressed persons, it was suggested that the immune system participates in CNS xenograft failures (Czech et al, 1997). Taken together, these findings indicate that the CNS is accessible to immune cells and that local immune responses within the CNS are regulated by several mechanisms.…”

Section: The Central Nervous System As An Immune-privileged Sitementioning

confidence: 99%

Macrophages and Microglia in Central Nervous System Injury: Are They Helpful or Harmful?

Schwartz

2003

J Cereb Blood Flow Metab

138

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Summary:Inflammation has been widely perceived as participating in the etiology of acute and chronic neurodegenerative conditions. Accordingly, in the context of traumatic injuries or chronic neurodegenerative diseases in the central nervous system (CNS), activated microglia have been viewed as detrimental and attempts have been made to treat both conditions by antiinflammatory therapy. Recent studies have suggested that microglia act as stand-by cells in the service of both the immune and the nervous systems. In the healthy CNS these cells are quiescent, but in the event of injury to axons or cell bodies they exercise their neural function by buffering harmful self-compounds and clearing debris from the damaged site, and their immune function by providing immune-related requirements for recovery. Proper regulation of the inflammatory (autoimmune) response to injury will arrest degeneration and promote regrowth, whereas inappropriate regulation will lead to ongoing degeneration. Regulation is achieved by the operation of a T cell-mediated response directed to abundant selfantigens residing in the damaged site. Since this immunedependent mechanism was found to protect against glutamate toxicity (a major factor in neurodegenerative disorders), boosting of this response might constitute the basis for development of a therapeutic vaccination against neurodegenerative diseases, all of which exhibit similar pathways and patterns of progression.

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Section: The Central Nervous System As An Immune-privileged Sitementioning

confidence: 99%

Macrophages and Microglia in Central Nervous System Injury: Are They Helpful or Harmful?

Schwartz

2003

J Cereb Blood Flow Metab

138

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“…First, the glial cells within the brain can secrete cytokines and chemokines as well as participate in antigen presentation (Ransohoff and Tani, 1998;O'Keefe et al, 1999). Furthermore, the failure of most long term central nervous system xenografts are the result of immune responses within the brain (Czech et al, 1997). From a disease perspective, multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE) clearly demonstrate the devastation brought about by cellular and humoral immune responses within the central nervous system.…”

Section: Introductionmentioning

confidence: 99%

Immunobiology of the blood-brain barrier

Miller¹

1999

J Neurovirol

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The brain microvessel endothelial cells (BMVEC) that form the blood-brain barrier are uniquely positioned to in¯uence immune responses within the central nervous system. As the biological interface separating the blood from the brain extracellular¯uid, BMVEC regulate the entry of leukocytes into the brain. In addition, through the release of various soluble factors that affect immune responses, BMVEC may modulate immune responses in the brain. This review addresses the interplay between the immune system and the blood-brain barrier as it relates to the regulation of CNS defense and immunity.

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“…Czech, et al have also found that cyclosporine administration could not prevent or delay the rejection of xenogeneic bovine endothelial cells grafted into the rat CNS [250]. Since cyclosporine treatment acts primarily to inhibit T lymphocyte-mediated immunity [251,252], these findings indicate the involvement of other arms of the immune system, such as innate immunity, in MSC graft rejection.…”

Section: Activation Of Innate Immune Response With Intracerebral Msc mentioning

confidence: 99%

Mesenchymal Stem Cell-Based Therapies for Parkinson’s Disease: Progress, Controversies and Lessons for the Future

Khoo¹,

Tao²,

D.F.³

2011

J Stem Cell Res Ther

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Scientific and clinical research interest in mesenchymal stem cells (MSCs) has increased exponentially since the identification of MSCs in the bone marrow. It is now recognized that MSCs possess the in vitro characteristics of stem cells with the abilities to proliferate, symmetrically divide, and produce multi-lineage mesodermal derivatives, making MSCs attractive candidates for use in potential cellular therapies. Furthermore, MSCs can be relatively easily isolated and expanded in culture with low tumorigenicity and teratoma formation, and have been reported to display immunomodulatory properties that may be advantageous in clinical transplantation. Discovery of the ability of MSCs to differentiate into cells of non-mesodermal tissues, particularly neural cells, has also raised the possibility of utilizing MSCs in regenerative and reparative therapies for neurological disorders. However, a number of hurdles remain to be resolved, including conflicting findings concerning the capacity of MSCs to suppress immune responses and contribute to multiple tissue lineages, highlighting the need for a greater understanding of mechanisms underlying the observed phenomena. In this review we will discuss: (1) recent advances in our understanding of MSC plasticity/transdifferentiation and immunomodulatory properties; (2) evidence for cell-based therapies, in particular MSC-based therapies for Parkinson's disease; and (3) current challenges and potential strategies for the utilization of MSCs in the treatment of Parkinson's disease.

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The Influence of Xenotransplant Immunogenicity and Immunosuppression on Host MHC Expression in the Rat CNS

Cited by 40 publications

References 27 publications

Macrophages and Microglia in Central Nervous System Injury: Are They Helpful or Harmful?

Macrophages and Microglia in Central Nervous System Injury: Are They Helpful or Harmful?

Immunobiology of the blood-brain barrier

Mesenchymal Stem Cell-Based Therapies for Parkinson’s Disease: Progress, Controversies and Lessons for the Future

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