Porcine neural xenografts in the immunocompetent rat: immune response following grafting of expanded neural precursor cells

Armstrong, Richard J. E.; Harrower, Timothy; Hurelbrink, Carrie B.; McLaughin, M.; Ratcliffe, Emma; Tyers, Pam; Richards, Andrew; Dunnett, Stephen B.; Rosser, Anne Elizabeth; Barker, Roger A.

doi:10.1016/s0306-4522(01)00273-1

Cited by 68 publications

(48 citation statements)

References 70 publications

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“…It has been reported that immunogenicity of porcine neural cell suspensions used for i.c. xenotransplantation is reduced when stem cell mitogens are used to expand precursor cells (37). Several arguments are in favor of an advantage of the use of hSDSCs when compared with other cell therapy-based strategies.…”

Section: Discussionmentioning

confidence: 99%

Effect of Human Skin-Derived Stem Cells on Vessel Architecture, Tumor Growth, and Tumor Invasion in Brain Tumor Animal Models

et al. 2007

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Glioblastomas represent an important cause of cancer-related mortality with poor survival. Despite many advances, the mean survival time has not significantly improved in the last decades. New experimental approaches have shown tumor regression after the grafting of neural stem cells and human mesenchymal stem cells into experimental intracranial gliomas of adult rodents. However, the cell source seems to be an important limitation for autologous transplantation in glioblastoma. In the present study, we evaluated the tumor targeting and antitumor activity of human skin-derived stem cells (hSDSCs) in human brain tumor models. The hSDSCs exhibit tumor targeting characteristics in vivo when injected into the controlateral hemisphere or into the tail vein of mice. When implanted directly into glioblastomas, hSDSCs distributed themselves extensively throughout the tumor mass, reduced tumor vessel density, and decreased angiogenic sprouts. In addition, transplanted hSDSCs differentiate into pericyte cell and release high amounts of human transforming growth factor-B1 with low expression of vascular endothelial growth factor, which may contribute to the decreased tumor cell invasion and number of tumor vessels. In long-term experiments, the hSDSCs were also able to significantly inhibit tumor growth and to prolong animal survival. Similar behavior was seen when hSDSCs were implanted into two different tumor models, the chicken embryo experimental glioma model and the transgenic Tyrp1-Tag mice. Taken together, these data validate the use of hSDSCs for targeting human brain tumors. They may represent therapeutically effective cells for the treatment of intracranial tumors after autologous transplantation.

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Section: Discussionmentioning

confidence: 99%

Effect of Human Skin-Derived Stem Cells on Vessel Architecture, Tumor Growth, and Tumor Invasion in Brain Tumor Animal Models

et al. 2007

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“…Furthermore, when the rats were grafted using the same process but the hosts were immunosuppressed with tacrolimus, massive gliosis developed with no retinal cells. 90,91 Overall, the immunology of grafted stem cells has not been extensively studied in depth, 92 but is of importance. When grafting tissue of different immunological disparity, there is local cytokine production that may affect the stability and development of stem cells.…”

Section: Stem Cellsmentioning

confidence: 99%

Immune problems in central nervous system cell therapy

Barker¹,

Widner

2004

Neurotherapeutics

168

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Summary:Transplantation of cells and tissues to the mammalian brain and CNS has revived the interest in the immunological status of brain and its response to grafted tissue. The previously held view that the brain was an absolute "immunologically privileged site" allowing indefinite survival without rejection of grafts of cells has proven to be wrong. Thus, the brain should be regarded as a site where immune responses can occur, albeit in a modified form, and under certain circumstances these are as vigorous as those seen in other peripheral sites. Clinical cell transplant trials have now been performed in Parkinson's disease, Huntington's disease, demyelinating diseases, retinal disorders, stroke, epilepsy, and even deafness, and normally are designed as cell replacement strategies, although implantation of genetically modified cells for supplementation of growth factors has also been tried. In addition, some disorders of the CNS for which cell therapies are being considered have an immunological basis, such as multiple sclerosis, which further complicates the situation. Embryonic neural tissue allografted into the CNS of animals and patients with neurodegenerative conditions survives, makes and receives synapses, and ameliorates behavioral deficits. The use of aborted human tissue is logistically and ethically complicated, which has lead to the search for alternative sources of cells, including xenogeneic tissue, genetically modified cells, and stem cells, all of which can and will induce some level of immune reaction. We review some of the immunological factors involved in transplantation of cells to CNS.

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“…In addition, NSCs express increased levels of MHC classes I and II after stimulation with proinflammatory cytokines or after exposure to a foreign environment (McLaren et al 2001;Modo et al 2002Modo et al , 2003Al Nimer et al 2004;Mammolenti et al 2004). Intracerebral neural xenografts have been shown to trigger responses involving host cytotoxic T-lymphocytes, microglia/macrophages, immunoglobulin M and complement (Armstrong et al 2001), and it is therefore not surprising that rejections of neural allografts and xenografts were observed in several studies (Sloan et al 1991). Furthermore, it is probable that studies of transplanted inbred animals do not provide us with a correct picture of the expected immune reaction in humans, where rejections are more likely to occur, i.e.…”

Section: Myth 8: Stem Cells Do Not Provoke An Immune Responsementioning

confidence: 99%

Stem cell myths

Magnus

Liu

Parker

et al. 2007

Phil. Trans. R. Soc. B

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Stem cells, although difficult to define, hold great promise as tools for understanding development and as therapeutic agents. However, as with any new field, uncritical enthusiasm can outstrip reality. In this review, we have listed nine common myths that we believe affect our approach to evaluating stem cells for therapy. We suggest that careful consideration needs to be given to each of these issues when evaluating a particular cell for its use in therapy. Data need to be collected and reported for failed as well as successful experiments and a rigorous scientific approach taken to evaluate the undeniable promise of stem cell biology.

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Porcine neural xenografts in the immunocompetent rat: immune response following grafting of expanded neural precursor cells

Cited by 68 publications

References 70 publications

Effect of Human Skin-Derived Stem Cells on Vessel Architecture, Tumor Growth, and Tumor Invasion in Brain Tumor Animal Models

Effect of Human Skin-Derived Stem Cells on Vessel Architecture, Tumor Growth, and Tumor Invasion in Brain Tumor Animal Models

Immune problems in central nervous system cell therapy

Stem cell myths

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