Combining physical &amp; cognitive training with iPSC-derived dopaminergic neuron transplantation promotes graft integration &amp; better functional outcome in parkinsonian marmosets

Daadi, Etienne W.; Daadi, Elyas S.; Oh, Thomas; Li, Mingfeng; Kim, Jeffrey; Daadi, Marcel M.

doi:10.1016/j.expneurol.2024.114694

Cited by 2 publications

(1 citation statement)

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“…Although these studies indicate partially successful engraftment, the data are restricted to only 1–3 months after transplantation, and the immune responses are not well elucidated. In a recent study of parkinsonian marmosets transplanted with iPSC-derived dopaminergic neurons, functional engraftment was observed at 6 months after transplantation under the continuous immunosuppression of tacrolimus (also known as FK506) until necropsy (Daadi et al 2024 ). It is still unknown how immune responses change over time after transplantation under long-term continuous administration of CsA.…”

Section: Introductionmentioning

confidence: 99%

Continuous immunosuppression is required for suppressing immune responses to xenografts in non-human primate brains

Feng,

Zhang,

et al. 2024

Cell Regen

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Continuous immunosuppression has been widely used in xenografts into non-human primate brains. However, how immune responses change after transplantation in host brains under continuous immunosuppressive administration and whether immunosuppression can be withdrawn to mitigate side effects remain unclear. Human induced neural stem/progenitor cells (iNPCs) have shown long-term survival and efficient neuronal differentiation in primate brains. Here, we evaluate the immune responses in primate brains triggered by human grafts. The results show that the immune responses, including the evident activation of microglia and the strong infiltration of lymphocytes (both T- and B-cells), are caused by xenografts at 4 months post transplantation (p.t.), but significantly reduced at 8 months p.t. under continuous administration of immunosuppressant Cyclosporin A. However, early immunosuppressant withdrawal at 5 months p.t. results in severe immune responses at 10 months p.t. These results suggest that continuous long-term immunosuppression is required for suppressing immune responses to xenografts in primate brains.

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Section: Introductionmentioning

confidence: 99%

Continuous immunosuppression is required for suppressing immune responses to xenografts in non-human primate brains

Feng,

Zhang,

et al. 2024

Cell Regen

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Human stem cell transplantation for Parkinson’s disease: A systematic review ofin situsurvival and maturation of progenitors derived from human embryonic or induced stem cells in Parkinsonian models

Comini,

Dowd

2024

Preprint

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Stem cell-based brain repair is a promising emergent therapy for Parkinson's which is based on years of foundational research using human fetal donors as a cell source. Unlike current therapeutic options for patients, this approach has the potential to provide long-term stem cell-derived reconstruction and restoration of the dopaminergic input to denervated regions of the brain allowing for restoration of certain functions to patients. The ultimate clinical success of stem cell-derived brain repair will depend on both the safety and efficacy of the approach, and the latter is dependent on the ability of the transplanted cells to survive and differentiate into functional dopaminergic neurons in the Parkinsonian brain. Because the pre-clinical literature suggests that there is a considerable variability in survival and differentiation between studies, the aim of this systematic review was to assess these parameters in human stem-derived dopaminergic progenitor transplant studies in animal models of Parkinson's. To do so, a defined systematic search of the PubMed database was completed to identify relevant studies published up to March 2024. After screening, 76 articles were included in the analysis from which 178 separate transplant studies were identified. From these, graft survival could be assessed in 52 studies and differentiation in 129 studies. Overall, we found that graft survival ranged from <1% to 500% of cells transplanted, with a median of 51% of transplanted cells surviving in the brain; while dopaminergic differentiation of the cells ranged from 0% to 46% of cells transplanted with a median of 3%. This systematic review suggests that there is considerable scope for improvement in the differentiation of stem cell-derived dopaminergic progenitors in order to maximize the therapeutic potential of this approach for patients.

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Combining physical & cognitive training with iPSC-derived dopaminergic neuron transplantation promotes graft integration & better functional outcome in parkinsonian marmosets

Cited by 2 publications

References 113 publications

Continuous immunosuppression is required for suppressing immune responses to xenografts in non-human primate brains

Continuous immunosuppression is required for suppressing immune responses to xenografts in non-human primate brains

Human stem cell transplantation for Parkinson’s disease: A systematic review ofin situsurvival and maturation of progenitors derived from human embryonic or induced stem cells in Parkinsonian models

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