Variable behavior and complications of autologous bone marrow mesenchymal stem cells transplanted in experimental autoimmune encephalomyelitis

Grigoriadis, Nikolaos; Lourbopoulos, Athanasios; Lagoudaki, Roza; Frischer, Josa M.; Polyzoidou, Eleni; Touloumi, Olga; Simeonidou, Constantina; Deretzi, Georgia; Kountouras, Jannis; Spandou, Evangelia; Kotta, Konstantia; Karkavelas, Georgios; Tascos, Nikolaos; Lassmann, Hans

doi:10.1016/j.expneurol.2011.02.021

Cited by 91 publications

(74 citation statements)

References 72 publications

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“…In our study, we observed dissemination of MSC-NPs throughout the brain and spinal cord, where cells were primarily associated with the meninges near inflammatory foci, along with some migration into the parenchyma. We did not observe any cellular masses such as those recently reported following intracerebroventricular transplantation of MSCs [33]. Overall, the intrathecal application of MSC-NPs was well tolerated in mice with EAE.…”

Section: Discussionsupporting

confidence: 60%

Clinical and pathological effects of intrathecal injection of mesenchymal stem cell-derived neural progenitors in an experimental model of multiple sclerosis

Harris

Yan

Vyshkina

et al. 2012

Journal of the Neurological Sciences

114

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Section: Discussionsupporting

confidence: 60%

Clinical and pathological effects of intrathecal injection of mesenchymal stem cell-derived neural progenitors in an experimental model of multiple sclerosis

Harris

Yan

Vyshkina

et al. 2012

Journal of the Neurological Sciences

114

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“…Here, the MSCs appeared to alter the activation program of the developing T cells, but the precise mechanisms of MSC-induced IL-2 production and downstream effector function remain undefined. In another report of MSC modulation of neuroinflammatory autoimmune disease, MSCs were found to ameliorate mild MOG-induced EAE, but worsen the severe form, with intracerebroventricular (ICT) injection into mice [78] . In almost two-thirds of severe-EAE animals, these MSCs migrated into the parenchyma and formed masses characterized by focal inflammation, demyelination, axon loss, and collagen and fibronectin deposits.…”

mentioning

confidence: 99%

Mesenchymal stem cells: Emerging mechanisms of immunomodulation and therapy

Glenn¹

2014

WJSC

360

304

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Mesenchymal stem cells (MSCs) are a pleiotropic population of cells that are self-renewing and capable of differentiating into canonical cells of the mesenchyme, including adipocytes, chondrocytes, and osteocytes. They employ multi-faceted approaches to maintain bone marrow niche homeostasis and promote wound healing during injury. Biomedical research has long sought to exploit their pleiotropic properties as a basis for cell therapy for a variety of diseases and to facilitate hematopoietic stem cell establishment and stromal reconstruction in bone marrow transplantation. Early results demonstrated their usage as safe, and there was little host response to these cells. The discovery of their immunosuppressive functions ushered in a new interest in MSCs as a promising therapeutic tool to suppress inflammation and down-regulate pathogenic immune responses in graft-versus-host and autoimmune diseases such as multiple sclerosis, autoimmune diabetes, and rheumatoid arthritis. MSCs produce a large number of soluble and membrane-bound factors, some of which inhibit immune responses. However, the full range of MSC-mediated immune-modulation remains incompletely understood, as emerging reports also reveal that MSCs can adopt an immunogenic phenotype, stimulate immune cells, and yield seemingly contradictory results in experimental animal models of inflammatory disease. The present review describes the large body of literature that has been accumulated on the fascinating biology of MSCs and their complex effects on immune responses.

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“…48,49 The relevance of this to stroke, where inflammatory responses are likely to be less intense, or indeed absent by late times after the incident, is unclear, and no clinical evidence of such a response has been observed to date.…”

Section: Late Subacute or Chronic Strokementioning

confidence: 99%

Clinical trial design for stem cell therapies in stroke: What have we learned?

Muir

2017

Neurochemistry International

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Stem cells of various sources have been investigated in a series of small, safety and feasibility-focused studies over the past 15 years. Understanding of mechanisms of action has evolved and the trial paradigms have become focused on two different approaches -one being an early subacute delivery of cells to reduce acute tissue injury and modify the tissue environment in a direction favourable to reparative processes (for example by being anti-inflammatory, antiapoptotic, and encouraging endogenous stem cell mobilisation); the other exploring later delivery of cells during the recovery phase after stroke to modulate the local environment in favour of angiogenesis and neurogenesis. The former approach has generally investigated intravenous or intra-arterial delivery of cells with an expected paracrine mode of action and no expected engraftment within the brain. The latter has explored direct intracerebral implantation adjacent to the infarct. Several relevant trials have been conducted, including two controlled trials of intravenously delivered bone marrow-derived cells in the early subacute stage, and two small singlearm phase 1 trials of intracerebrally implanted cells. The findings of these studies and their implications for future trial design are considered.Introduction:

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Variable behavior and complications of autologous bone marrow mesenchymal stem cells transplanted in experimental autoimmune encephalomyelitis

Cited by 91 publications

References 72 publications

Clinical and pathological effects of intrathecal injection of mesenchymal stem cell-derived neural progenitors in an experimental model of multiple sclerosis

Clinical and pathological effects of intrathecal injection of mesenchymal stem cell-derived neural progenitors in an experimental model of multiple sclerosis

Mesenchymal stem cells: Emerging mechanisms of immunomodulation and therapy

Clinical trial design for stem cell therapies in stroke: What have we learned?

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