Immunoregulatory Properties of Neural Stem Cells

Michel-Monigadon, Delphine; Brachet, Philippe; Neveu, Isabelle; Naveilhan, Philippe

doi:10.2217/imt.11.49

Cited by 12 publications

(9 citation statements)

References 22 publications

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“…A majority of reports focus on cell products from pigs as the most likely sources of cells for transplantation into humans. For example, fetal porcine neuroblasts were systematically rejected after intracerebral administration for the treatment of neurodegenerative diseases in other animal hosts, especially non-human primates [22]. Immunosuppression was required and produced secondary effects.…”

Section: Chimeric Animals and Xenotransplantationmentioning

confidence: 99%

Large animal models for stem cell therapy

2013

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The field of regenerative medicine is approaching translation to clinical practice, and significant safety concerns and knowledge gaps have become clear as clinical practitioners are considering the potential risks and benefits of cell-based therapy. It is necessary to understand the full spectrum of stem cell actions and preclinical evidence for safety and therapeutic efficacy. The role of animal models for gaining this information has increased substantially. There is an urgent need for novel animal models to expand the range of current studies, most of which have been conducted in rodents. Extant models are providing important information but have limitations for a variety of disease categories and can have different size and physiology relative to humans. These differences can preclude the ability to reproduce the results of animal-based preclinical studies in human trials. Larger animal species, such as rabbits, dogs, pigs, sheep, goats, and non-human primates, are better predictors of responses in humans than are rodents, but in each case it will be necessary to choose the best model for a specific application. There is a wide spectrum of potential stem cell-based products that can be used for regenerative medicine, including embryonic and induced pluripotent stem cells, somatic stem cells, and differentiated cellular progeny. The state of knowledge and availability of these cells from large animals vary among species. In most cases, significant effort is required for establishing and characterizing cell lines, comparing behavior to human analogs, and testing potential applications. Stem cell-based therapies present significant safety challenges, which cannot be addressed by traditional procedures and require the development of new protocols and test systems, for which the rigorous use of larger animal species more closely resembling human behavior will be required. In this article, we discuss the current status and challenges of and several major directions for the future development of large animal models to facilitate advances in stem cell-based regenerative medicine.

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Section: Chimeric Animals and Xenotransplantationmentioning

confidence: 99%

Large animal models for stem cell therapy

2013

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“…The presence of an anti-inflammatory environment, induced by IL-10, significantly enhanced adult NSC-induced functional recovery from EAE [65]. However, transplanted NSCs can also regulate immune cell functions in a dose-dependent manner [63, 67, 68]. In vitro cultured neurospheres significantly inhibited proliferation of MOG-specific lymph node cells and switched their cytokine profile from Th1 to Th2 [63].…”

Section: Microglia In Msmentioning

confidence: 99%

Animal Models of MS Reveal Multiple Roles of Microglia in Disease Pathogenesis

Gao

Tsirka

2011

Neurology Research International

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Multiple sclerosis (MS) is a progressive inflammatory and demyelinating disease that affects more than 2.5 million people worldwide every year. Current therapies use mostly disease-modifying drugs, focusing on blocking and regulating systemic functions and the central nervous system (CNS) infiltration of immune cells; however, these therapies only attenuate or delay MS symptoms, but are not effective in halting the disease progression. More recent evidence indicated that regulation of inflammation within the CNS might be a better way to approach the treatment of the disease and microglia, the resident immune cells, may be a promising target of therapeutic studies. Microglia activation classically accompanies MS development, and regulation of microglia function changes the outcome of the disease. In this paper, we review the contributions of microglia to MS pathogenesis and discuss microglial functions in antigen presentation, cytokine release, and phagocytosis. We describe data both from animal and human studies. The significant impact of the timing, intensity, and differentiation fate of activated microglia is discussed, as they can modulate MS outcomes and potentially be critically modified for future therapeutic studies.

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“…However, it has been noted that MSCs that reach tumor stroma can contribute to tumor development through the mechanisms of creating a niche to support cancer stem cells, promoting angiogenesis, and/or promoting cancer metastasis [36][37][38]. Both MSCs and NSCs display immunosuppressive effects [39][40][41][42], which may promote tumor growth by inhibiting the "tumor surveillance" functions of the immune system, thus compromising the effectiveness of using these cellular vehicles for cancer treatment. Unlike MSCs and NSCs, there is no report of immunosuppressive effects for EPCs.…”

Section: Discussionmentioning

confidence: 99%

Antitumor Effects of CD40 Ligand-Expressing Endothelial Progenitor Cells Derived From Human Induced Pluripotent Stem Cells in a Metastatic Breast Cancer Model

Purwanti

Chen

Lam

et al. 2014

Stem Cells Translational Medicine

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Given their intrinsic ability to home to tumor sites, endothelial progenitor cells (EPCs) are attractive as cellular vehicles for targeted cancer gene therapy. However, collecting sufficient EPCs is one of the challenging issues critical for effective clinical translation of this new approach. In this study, we sought to explore whether human induced pluripotent stem (iPS) cells could be used as a reliable and accessible cell source to generate human EPCs suitable for cancer treatment. We used an embryoid body formation method to derive CD133 + CD34+ EPCs from human iPS cells. The generated EPCs expressed endothelial markers such as CD31, Flk1, and vascular endothelial-cadherin without expression of the CD45 hematopoietic marker. After intravenous injection, the iPS cell-derived EPCs migrated toward orthotopic and lung metastatic tumors in the mouse 4T1 breast cancer model but did not promote tumor growth and metastasis. To investigate their therapeutic potential, the EPCs were transduced with baculovirus encoding the potent T cell costimulatory molecule CD40 ligand. The systemic injection of the CD40 ligand-expressing EPCs stimulated the secretion of both tumor necrosis factor-a and interferon-g and increased the caspase 3/7 activity in the lungs with metastatic tumors, leading to prolonged survival of the tumor bearing mice. Therefore, our findings suggest that human iPS cell-derived EPCs have the potential to serve as tumor-targeted cellular vehicles for anticancer gene therapy. STEM CELLS TRANSLATIONAL MEDICINE 2014;3:923-935

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Immunoregulatory Properties of Neural Stem Cells

Cited by 12 publications

References 22 publications

Large animal models for stem cell therapy

Large animal models for stem cell therapy

Animal Models of MS Reveal Multiple Roles of Microglia in Disease Pathogenesis

Antitumor Effects of CD40 Ligand-Expressing Endothelial Progenitor Cells Derived From Human Induced Pluripotent Stem Cells in a Metastatic Breast Cancer Model

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