Survival of transplanted human neural stem cell line (ReNcell VM) into the rat brain with and without immunosuppression

Hovakimyan, Marina; Müller, Jana; Wree, Andreas; Ortinau, Stefanie; Rolfs, Arndt; Schmitt, Oliver

doi:10.1016/j.aanat.2012.05.003

Cited by 22 publications

(24 citation statements)

References 51 publications

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“…Similar to our previous work, where we were able to observe therapeutic efficacy and stimulation of endogenous repair, we have stuck to this protocol and avoided immunosuppressive therapy, and thus possible potential effects on stroke progression and cell distribution [37]. Furthermore, our investigations where designed as a proof-of-concept study with a survival time of only 14 days, which is short compared to the 6 weeks used by, for example, Hovakimyan et al [36]. …”

Section: Discussionmentioning

confidence: 86%

“…This is a problem affecting all studies testing human stem cells in rodent systems; however, even allogeneic transplantation is being discussed as including the risk of immune rejection [35]. There are conflicting reports regarding the need for immunosuppressive therapy after xenograft stem-cell therapy for cell survival and differentiation, and it is still unclear whether ASCs, despite their immunomodulatory capacities, may elicit systemic immune reactions [36]. Similar to our previous work, where we were able to observe therapeutic efficacy and stimulation of endogenous repair, we have stuck to this protocol and avoided immunosuppressive therapy, and thus possible potential effects on stroke progression and cell distribution [37].…”

Section: Discussionmentioning

confidence: 99%

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The effect of adipose tissue-derived stem cells in a middle cerebral artery occlusion stroke model depends on their engraftment rate

et al. 2017

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BackgroundIn the field of experimental stem cell therapy, intra-arterial (IA) delivery yields the best results concerning, for example, migrated cell number at the targeted site. However, IA application also appears to be associated with increased mortality rates and infarction. Since many rodent studies systemically apply 1 × 106 cells, this could also be a consequence of engrafted cell number. The aim of this study was therefore to investigate the effect of different doses of adipose tissue-derived stem cells (ASCs) on engraftment rates and stroke outcome measured in vivo using 9.4-T high-field magnetic resonance imaging (MRI).MethodsMale Wistar rats (n = 43) underwent a middle cerebral artery occlusion (MCAo) for 45 or 90 min, followed by IA delivery of either saline or 1 × 106, 3 × 105, or 5 × 104 ASCs pre-labelled with very small superparamagnetic iron oxide particles (VSOPs). MRI (9.4-T) analysis was performed 48 h and 9 days post-MCAo. Lesion volumes were assessed by analysis of T2-weighted images and cell signal tracking showing cell engraftment and active cell migration by an improved T2*-analysis.ResultsThe ASC-derived signal intensity increased in the affected hemisphere 48 h post MCAo with injected cell number (p < 0.05). The analysis of stroke volumes revealed an increased infarction after injection of 1 × 106 ASCs compared to controls or application of 5 × 104 ASCs (p < 0.05). At 9 days post-MCAo, injection of 3 × 105 ASCs resulted in reduced infarct volumes (p < 0.05). Correspondingly, MRI analysis revealed no changes in cell numbers between both MRI examinations but showed active ASC migration to the site of infarction.ConclusionOur results confirm that IA injection is an efficient way of targeting damaged brain tissue but its usefulness strongly depends on the right dose of delivered stem cells since this factor has a strong influence on migration rate and infarct volume, with better results for doses below 1 × 106 cells. Future challenges will include the determination of therapeutic doses for best cellular engraftment and stroke outcome.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0545-y) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

The effect of adipose tissue-derived stem cells in a middle cerebral artery occlusion stroke model depends on their engraftment rate

et al. 2017

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“…For example, studies show immunosuppression to increase xenograft (human to rat) survival qualitatively [29] and quantitatively [30], but allograft transplantation into the striatum was not affected between immune-deficient/immuno-competent mice [31] other than to favor neuron differentiation [32]. The brain is now no longer considered a completely immuno-privileged region there is a degree of immune privilege, and the immune response is a major consideration for cell therapy [33].…”

Section: Toxicity and Host Responsementioning

confidence: 98%

Prospects for polymer therapeutics in Parkinson's disease and other neurodegenerative disorders

Newland

Werner

et al. 2015

Progress in Polymer Science

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a b s t r a c tParkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons and represents a growing health burden to western societies. Like many neurodegenerative disorders the cause is unknown, however, as the pathogenesis becomes ever more elucidated, it is becoming clear that effective delivery is a key issue for new therapeutics. The versatility of today's polymerization techniques allows the synthesis of a wide range of polymer materials which hold great potential to aid in the delivery of small molecules, proteins, genetic material or cells. In this review, we capture the recent advances in polymer based therapeutics of the central nervous system (CNS). We place the advances in historical context and, furthermore, provide future prospects in line with newly discovered advancements in the understanding of PD and other neurodegenerative disorders. This review provides researchers in the field of polymer chemistry and materials science an up-to-date understanding of the requirements placed upon materials designed for use in the CNS aiding the focus of polymer therapeutic design.

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“…Consequently, it reduces the acquired immune response and promotes survival of grafted neural progenitor cells (NPCs) in the brain (Hovakimyan et al, 2012). CsA, however, inhibits the maturation of NPCs (Guo et al, 2007) and its long-term administration can cause nephrotoxicity, liver dysfunction and a compromised host (Burdmann et al, 2003;Grub et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

X-linked severe combined immunodeficiency (X-SCID) rats for xeno-transplantation and behavioral evaluation

Samata

Kikuchi

Miyawaki

et al. 2015

Journal of Neuroscience Methods

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Survival of transplanted human neural stem cell line (ReNcell VM) into the rat brain with and without immunosuppression

Cited by 22 publications

References 51 publications

The effect of adipose tissue-derived stem cells in a middle cerebral artery occlusion stroke model depends on their engraftment rate

The effect of adipose tissue-derived stem cells in a middle cerebral artery occlusion stroke model depends on their engraftment rate

Prospects for polymer therapeutics in Parkinson's disease and other neurodegenerative disorders

X-linked severe combined immunodeficiency (X-SCID) rats for xeno-transplantation and behavioral evaluation

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