The search for a curative cell therapy in Parkinson's disease

Goya, Rocío Laguna; Tyers, Pam; Barker, Roger A.

doi:10.1016/j.jns.2007.09.006

Cited by 32 publications

(13 citation statements)

References 115 publications

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“…Second, current clinical transplantation protocols for patients with PD are profoundly limited, for example, by the use of fresh embryonic graft material derived from human abortions and by uneven and incomplete graft‐derived TH‐positive innervation from ectopically placed intrastriatal nigral grafts (Bjorklund and Lindvall, 2000; Dunnett et al, 2001). Third, more than 20 years of experimental experience with DA grafts in well‐characterized animal models of PD have accumulated a significant body of knowledge about DA graft survival, integration, and functional recovery (Bjorklund et al, 2003; Winkler and Kirik, 2004; Deierborg et al, 2008; Laguna et al, 2008).…”

mentioning

confidence: 99%

Survival and early functional integration of dopaminergic progenitor cells following transplantation in a rat model of Parkinson's disease

Hahn¹,

Timmer²,

Nikkhah³

2009

J of Neuroscience Research

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Dopaminergic (DA) grafts in rat models of Parkinson's disease (PD) have previously been derived from embryonic day (E) 14 grafts. Because there is an increasing interest in the restorative capacity of DA stem and progenitor cells, in the present study we examined the survival and early and late functional behavioral effects of DA progenitor cells derived from E12, E13, E14, and E15 grafts transplanted into rats with unilateral 6-hydroxydopamin lesions. DA transplant-induced functional recovery was already observed in postural balancing reactions after 10 days and in stepping behavior after 13 days, that is, in spontaneous complex behaviors, and later, after 16 days, in the amphetamine-induced rotation test. Three distinct patterns of functional recovery could be observed at 6-9 weeks posttransplantation. First, behavioral improvements in drug-induced rotational asymmetry, stepping, and skilled forelimb behavior were directly related to DA neuron survival and TH-positive fiber reinnervation. Second, recovery in postural balancing reactions was closely related to a specific developmental time window of donor age, for example, only seen in E13 and E14 grafts. Finally, no functional graft effects were seen in the table lift test. Interestingly, DA neuron graft survival, TH-positive fiber outgrowth, and graft volume were significantly influenced by the developmental time window in which the DA progenitor cells were dissected from the ventral mesencephalon, that is, from E12, E13, E14, or E15 rat embryos. These data highlight the complexity of graft-host interactions and provide novel insights into the dynamics of DA progenitor graft-mediated functional recovery in animal models of Parkinson's disease. V V C 2009 Wiley-Liss, Inc.

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confidence: 99%

Survival and early functional integration of dopaminergic progenitor cells following transplantation in a rat model of Parkinson's disease

Hahn¹,

Timmer²,

Nikkhah³

2009

J of Neuroscience Research

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“…The standard protocol for transplanting dopamine neurons into a PD model involves grafting new neurons into the striatum, a heterotopic graft location (Laguna Goya et al, 2008). New dopamine cells grafted into the striatum lack the inputs that their physiological endogenous counterparts receive.…”

Section: The Nhp For Transplantation Therapy: Addressing the Graft Lomentioning

confidence: 99%

Advantages of nonhuman primates as preclinical models for evaluating stem cell-based therapies for Parkinson's disease

Grow¹,

McCarrey²,

Navara³

2016

Stem Cell Research

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The derivation of dopaminergic neurons from induced pluripotent stem cells brings new hope for a patient-specific, stem cell-based replacement therapy to treat Parkinson's disease (PD) and related neurodegenerative diseases; and this novel cell-based approach has already proven effective in animal models. However, there are several aspects of this procedure that have yet to be optimized to the extent required for translation to an optimal cell-based transplantation protocol in humans. These challenges include pinpointing the optimal graft location, appropriately scaling up the graft volume, and minimizing the risk of chronic immune rejection, among others. To advance this procedure to the clinic, it is imperative that a model that accurately and fully recapitulates characteristics most pertinent to a cell-based transplantation to the human brain is used to optimize key technical aspects of the procedure. Nonhuman primates mimic humans in multiple ways including similarities in genomics, neuroanatomy, neurophysiology, immunogenetics, and age-related changes in immune function. These characteristics are critical to the establishment of a relevant model in which to conduct preclinical studies to optimize the efficacy and safety of cell-based therapeutic approaches to the treatment of PD. Here we review previous studies in rodent models, and emphasize additional advantages afforded by nonhuman primate models in general, and the baboon model in particular, for preclinical optimization of cell-based therapeutic approaches to the treatment of PD and other neurodegenerative diseases. We outline current unresolved challenges to the successful application of stem cell therapies in humans and propose that the baboon model in particular affords a number of traits that render it most useful for preclinical studies designed to overcome these challenges.

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“…Recently, the transplantation of cells to the brain and/or spinal cord has been pursued as a potential curative treatment for a broad spectrum of human neurological diseases (107,108). Promising results have been achieved in clinical trials, but there is much work to be done before cell-based therapies can be practiced extensively.…”

Section: Neurological Diseasesmentioning

confidence: 99%

Microspheres for Cell Culture

2013

Microspheres and Microcapsules in Biotechnology

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The search for a curative cell therapy in Parkinson's disease

Cited by 32 publications

References 115 publications

Survival and early functional integration of dopaminergic progenitor cells following transplantation in a rat model of Parkinson's disease

Survival and early functional integration of dopaminergic progenitor cells following transplantation in a rat model of Parkinson's disease

Advantages of nonhuman primates as preclinical models for evaluating stem cell-based therapies for Parkinson's disease

Microspheres for Cell Culture

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