Immune response after striatal engraftment of fetal neuronal cells in patients with Huntington’s disease: Consequences for cerebral transplantation programs

Krebs, Simone; Trippel, Michael; Prokop, Thomas; Omer, Talib N.; Landwehrmeyer, B.; Nikkhah, Guido

doi:10.1111/j.1759-1961.2011.00018.x

Cited by 17 publications

(28 citation statements)

References 28 publications

(37 reference statements)

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“…The heterogeneity in the results was explained by differences in the efficacy readouts, injection sites, cell types and numbers, and the degree of differentiation and survival of the implanted cells . The preclinical and clinical literature shows that the long‐term survival of allogeneic and xenogeneic grafts can also be influenced by the presence, type and duration of systemic immunosuppressive therapy. The presence of the blood–brain barrier, the lack of expression of MHC antigens by parenchymal cells or the anti‐inflammatory properties of the central nervous system milieu have historically positioned the brain as an immune‐privileged site; however, it is now unquestionable that this immune privilege is only partial and may be overcome .…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, we monitored important clinical parameters, like the presence of donor‐specific antibodies in this PD xenotransplantation model, which may be critical in facilitating a good graft outcome. This could prove to be highly relevant because the de novo appearance of donor‐specific antibodies following fetal striatal allo‐ and xenotransplantation has been reported in recipients with PD and Huntington's disease , with unclear implications for clinical outcome. It is only by associating these fundamental approaches that we will be able to more efficiently translate new cell‐based therapies to patients with degenerative neurological diseases.…”

Section: Discussionmentioning

confidence: 99%

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Cell Therapy for Parkinson’s Disease: A Translational Approach to Assess the Role of Local and Systemic Immunosuppression

Badin¹,

Vadori²,

Vanhove³

et al. 2016

American Journal of Transplantation

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Neural transplantation is a promising therapeutic approach for neurodegenerative diseases; however, many patients receiving intracerebral fetal allografts exhibit signs of immunization to donor antigens that could compromise the graft. In this context, we intracerebrally transplanted mesencephalic pig xenografts into primates to identify a suitable strategy to enable long-term cell survival, maturation, and differentiation. Parkinsonian primates received WT or CTLA4-Ig transgenic porcine xenografts and different durations of peripheral immunosuppression to test whether systemic plus graft-mediated local immunosuppression might avoid rejection. A striking recovery of spontaneous locomotion was observed in primates receiving systemic plus local immunosuppression for 6 mo. Recovery was associated with restoration of dopaminergic activity detected both by positron emission tomography imaging and histological examination. Local infiltration by T cells and CD80/86+ microglial cells expressing indoleamine 2,3-dioxigenase were observed only in CTLA4-Ig recipients. Results suggest that in this primate neurotransplantation model, peripheral immunosuppression is indispensable to achieve the long-term survival of porcine neuronal xenografts that is required to study the beneficial immunomodulatory effect of local blockade of T cell costimulation. Abbreviations: ( 18

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cell Therapy for Parkinson’s Disease: A Translational Approach to Assess the Role of Local and Systemic Immunosuppression

Badin¹,

Vadori²,

Vanhove³

et al. 2016

American Journal of Transplantation

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“…This finding demonstrated alloimmunization towards donor antigens and called for a reconsideration of the immunosuppression given, pointing out the necessity of monitoring the immune response (Krystkowiak et al, 2007). In addition, the time at which anti-HLA appeared was highly variable as studied by Krebs et al (2011), as it could happen during immunosuppression or shortly after in a completely unpredictable way.…”

Section: Neuroinflammation Markers: Assessment In Cell-based Clinicalmentioning

confidence: 99%

Is the Immunological Response a Bottleneck for Cell Therapy in Neurodegenerative Diseases?

Salado-Manzano

Perpiñá

Straccia³

et al. 2020

Front. Cell. Neurosci.

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Neurodegenerative disorders such as Parkinson's (PD) and Huntington's disease (HD) are characterized by a selective detrimental impact on neurons in a specific brain area. Currently, these diseases have no cures, although some promising trials of therapies that may be able to slow the loss of brain cells are underway. Cell therapy is distinguished by its potential to replace cells to compensate for those lost to the degenerative process and has shown a great potential to replace degenerated neurons in animal models and in clinical trials in PD and HD patients. Fetal-derived neural progenitor cells, embryonic stem cells or induced pluripotent stem cells are the main cell sources that have been tested in cell therapy approaches. Furthermore, new strategies are emerging, such as the use of adult stem cells, encapsulated cell lines releasing trophic factors or cell-free products, containing an enriched secretome, which have shown beneficial preclinical outcomes. One of the major challenges for these potential new treatments is to overcome the host immune response to the transplanted cells. Immune rejection can cause significant alterations in transplanted and endogenous tissue and requires immunosuppressive drugs that may produce adverse effects. T-, B-lymphocytes and microglia have been recognized as the main effectors in striatal graft rejection. This review aims to summarize the preclinical and clinical studies of cell therapies in PD and HD. In addition, the precautions and strategies to ensure the highest quality of cell grafts, the lowest risk during transplantation and the reduction of a possible immune rejection will be outlined. Altogether, the wide-ranging possibilities of advanced therapy medicinal products (ATMPs) could make therapeutic treatment of these incurable diseases possible in the near future.

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“…In a German study, ten HD patients received foetal striatal transplantation [ 101 ]. Half of them developed HLA-antibodies of class I and II post-transplantation.…”

Section: Introductionmentioning

confidence: 99%

“…Overall, the outcome of HD neural transplantation studies was heterogeneous. For the few transplanted subjects who demonstrated clinical improvement, there was generally a corresponding improvement in their PET markers of graft survival or activity, apart from one subject in the German study who showed transient clinical improvement [ 101 ]. Conversely, none of the patients who did not improve clinically displayed an improvement in their PET parameters.…”

Section: Introductionmentioning

confidence: 99%

Restorative Strategies in Movement Disorders: the Contribution of Imaging

Lao–Kaim

Piccini

Tai

2017

Curr Neurol Neurosci Rep

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Purpose of ReviewThe purpose of this review was to review the imaging, particularly positron emission tomography (PET), findings in neurorestoration studies in movement disorders, with specific focus on neural transplantation in Parkinson’s disease (PD) and Huntington’s disease (HD).Recent FindingsPET findings in PD transplantation studies have shown that graft survival as reflected by increases in dopaminergic PET markers does not necessarily correlate with clinical improvement. PD patients with more denervated ventral striatum and more imbalanced serotonin-to-dopamine ratio in the grafted neurons tended to have worse outcome. In HD transplantation studies, variable graft survival and clinical responses may be related to host inflammatory/immune responses to the grafts.SummaryInformation gleaned from imaging findings in previous neural transplantation studies has been used to refine study protocol and patient selection in future trials. This includes identifying suitable candidates for transplantation using imaging markers, employing multiple and/or novel PET tracers to better assess graft functions and inflammatory responses to grafts.

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Immune response after striatal engraftment of fetal neuronal cells in patients with Huntington’s disease: Consequences for cerebral transplantation programs

Cited by 17 publications

References 28 publications

Cell Therapy for Parkinson’s Disease: A Translational Approach to Assess the Role of Local and Systemic Immunosuppression

Cell Therapy for Parkinson’s Disease: A Translational Approach to Assess the Role of Local and Systemic Immunosuppression

Is the Immunological Response a Bottleneck for Cell Therapy in Neurodegenerative Diseases?

Restorative Strategies in Movement Disorders: the Contribution of Imaging

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