Allogeneic grafts of fetal dopamine neurons: immunological reactions following active and adoptive immunizations

Shinoda, Masaki; Hudson, John L.; ̈mberg, Ingrid Stro; Hoffer, Barry J.; Moorhead, John W.; Olson, Lar̀s

doi:10.1016/0006-8993(95)00260-w

Cited by 31 publications

(17 citation statements)

References 31 publications

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“…The absence of transplant rejection in the particular allograft combination used in the present study is striking, especially in view of our recent studies which have demonstrated that similar allografts are rejected if the host is challenged by an orthotopic skin graft (Duan et al, 1995b) or if allogeneic spleen cells are included in the transplant preparation (Duan et al, 1997). Other studies have also shown that allogeneic neural grafts are rejected if the host animals is first immunized with an orthotopic skin graft (Nicholas et al, 1987;Rao et al, 1989;Sloan et al, 1990) or spleen cells (Mason et al, 1986;Shinoda et al, 1995). Nonetheless, the lack of a detrimental effect of the QUIN-lesion and inflammation on the survival of the allografts does not entirely exclude the possibility that implantation technique can affect the immune response.…”

Section: Discussionmentioning

confidence: 51%

Quinolinic acid‐induced inflammation in the striatum does not impair the survival of neural allografts in the rat

Duan

Widner

Cameron

et al. 1998

Eur J of Neuroscience

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It has been suggested that inflammation related to intracerebral transplantation surgery can affect the survival of intrastriatal neural allografts. To test this hypothesis, we transplanted dissociated embryonic mesencephalic tissue from one of two rat strains, Lewis (allogeneic grafts) or Sprague-Dawley (syngeneic grafts), to the striatum of Sprague-Dawley rats. The target striatum was either intact or had received a local injection of quinolinic acid 9 days earlier, in order to induce a marked inflammation. At 6 or 12 weeks after transplantation, there was no significant difference between the different groups regarding the number of surviving grafted tyrosine hydroxylase immunoreactive neurons. However, the graft volume of both the syngeneic and allogeneic implants was significantly larger in the quinolinate-lesioned than in the intact striatum. There were dramatically increased levels of expression of major histocompatibility complex class I and II antigens, marked infiltrates of macrophages, activated microglia and astrocytes, and accumulation of large numbers of CD4 and CD8 positive T-lymphocytes in the quinolinate-lesioned striatum. In contrast, these immunological markers were much less abundant around both syngeneic and allogeneic grafts placed in intact striatum. We conclude that severe inflammation caused by quinolinic acid does not lead to rejection of intrastriatal neural allografts.

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Section: Discussionmentioning

confidence: 51%

Quinolinic acid‐induced inflammation in the striatum does not impair the survival of neural allografts in the rat

Duan

Widner

Cameron

et al. 1998

Eur J of Neuroscience

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“…For quantitative analysis of MG activation, several parameters were studied using image analysis [23]. Signal intensity of each marker was evaluated using densitometry in material derived from animals in fetus and control groups.…”

Section: Quantitative Image Analysismentioning

confidence: 99%

Differential activation of astrocytes and microglia after spinal cord injury in the fetal rat

et al. 2005

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In the present study, collagen fibers and scar formation were seen in the severed spinal cords of adult rats, but scar formation was not seen in the fetal rat cordotomy group. Lack of inflammation and scar formation thus appear advantageous for regeneration of the fetal spinal cord. Between fetal and mature rats, chronological changes in the immunohistochemical reactions of astrocytes and microglia following cordotomy were compared, and the results confirmed many differences. The results of the present study suggest that the presence of activated glial cells around damaged central nervous tissue and the quick disappearance of these cells after injury are important for the repair of damaged central nervous system tissue, and that the role of glial cells in nerve regeneration can change depending on the level of maturity of glial cells or surrounding cells, site of injury, or the state of tissue around the injury.

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“…Experimental studies have shown that the injection of exogenous cells into the brain evokes an elevated host immune response (Barker et al., ; Duan, Cameron, Brundin, & Widner, ; Duan, Widner, Bjorklund, & Brundin, ; Hudson, Hoffman, Stromberg, Hoffer, & Moorhead, ; Shinoda et al., ). Additionally, in line with the prominent cell death seen immediately post‐transplantation, microglial activation, lymphocyte infiltration and major histocompatibility complex (MHC) expression all increased over the first 4 days post‐transplantation (Duan et al., ).…”

Section: Cellular Brain Repair For Parkinson's Disease – Potential Ofmentioning

confidence: 99%

“…Additionally, in line with the prominent cell death seen immediately post‐transplantation, microglial activation, lymphocyte infiltration and major histocompatibility complex (MHC) expression all increased over the first 4 days post‐transplantation (Duan et al., ). Moreover, the immune response may intensify overtime as the immune cells in the brain are not stationary and inactive, but rather provide a continuous inflammatory response (Shinoda et al., ). Postmortem analysis from the double‐blind, placebo‐controlled clinical trials, as well as an earlier study, detected prominent activated microglial staining around the graft site (Freed et al., ; Kordower et al., ; Olanow et al., ).…”

Section: Cellular Brain Repair For Parkinson's Disease – Potential Ofmentioning

confidence: 99%

Primary tissue for cellular brain repair in Parkinson's disease: Promise, problems and the potential of biomaterials

Moriarty

Parish

Dowd

2018

Eur J of Neuroscience

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The dopamine precursor, levodopa, remains the "gold standard" treatment for Parkinson's disease, and, although it provides superlative efficacy in the early stages of the disease, its long-term use is limited by the development of severe motor side effects and a significant abating of therapeutic efficacy. Therefore, there remains a major unmet clinical need for the development of effective neuroprotective, neurorestorative or neuroreparatory therapies for this condition. The relatively selective loss of dopaminergic neurons from the nigrostriatal pathway makes Parkinson's disease an ideal candidate for reparative cell therapies, wherein the dopaminergic neurons that are lost in the condition are replaced through direct cell transplantation into the brain. To date, this approach has been developed, validated and clinically assessed using dopamine neuron-rich foetal ventral mesencephalon grafts which have been shown to survive and reinnervate the denervated brain after transplantation, and to restore motor function. However, despite long-term symptomatic relief in some patients, significant limitations, including poor graft survival and the impact this has on the number of foetal donors required, have prevented this therapy being more widely adopted as a restorative approach for Parkinson's disease. Injectable biomaterial scaffolds have the potential to improve the delivery, engraftment and survival of these grafts in the brain through provision of a supportive microenvironment for cell adhesion, growth and immune shielding. This article will briefly review the development of primary cell therapies for brain repair in Parkinson's disease and will consider the emerging literature which highlights the potential of using injectable biomaterial hydrogels in this context.

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Allogeneic grafts of fetal dopamine neurons: immunological reactions following active and adoptive immunizations

Cited by 31 publications

References 31 publications

Quinolinic acid‐induced inflammation in the striatum does not impair the survival of neural allografts in the rat

Quinolinic acid‐induced inflammation in the striatum does not impair the survival of neural allografts in the rat

Differential activation of astrocytes and microglia after spinal cord injury in the fetal rat

Primary tissue for cellular brain repair in Parkinson's disease: Promise, problems and the potential of biomaterials

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