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Intrastriatal ventral mesencephalic xenografts of porcine tissue in rats : immune responses and functional effects

Larsson, L C LU ; Czech, K A; Brundin, P LU and Widner, H LU (2000) In Cell Transplantation 9(2). p.72-261
Abstract

Transplantation of neural tissue from other species has the potential to improve function in patients with neurodegenerative disorders. We investigated the functional effects of embryonic porcine dopaminergic neurons transplanted in a rat model of Parkinson's disease and the immune responses to the grafts in immunosuppressed and nonimmunosuppressed hosts. Twenty-three rats with unilateral 6-hydroxydopamine lesions received dissociated, 27-day-old embryonic porcine ventral mesencephalic tissue in the right striatum. Eighteen rats received cyclosporine (10 mg/kg, IP, daily) during the whole period of 14 weeks, in combination with prednisolone (20 mg/kg, IP, daily) the first 4 days. Five rats served as nonimmunosuppressed controls. All... (More)

Transplantation of neural tissue from other species has the potential to improve function in patients with neurodegenerative disorders. We investigated the functional effects of embryonic porcine dopaminergic neurons transplanted in a rat model of Parkinson's disease and the immune responses to the grafts in immunosuppressed and nonimmunosuppressed hosts. Twenty-three rats with unilateral 6-hydroxydopamine lesions received dissociated, 27-day-old embryonic porcine ventral mesencephalic tissue in the right striatum. Eighteen rats received cyclosporine (10 mg/kg, IP, daily) during the whole period of 14 weeks, in combination with prednisolone (20 mg/kg, IP, daily) the first 4 days. Five rats served as nonimmunosuppressed controls. All rats were tested for amphetamine-induced rotational behavior at 3-week intervals. Two immunosuppressed rats were excluded due to severe side effects of the treatment. Functional recovery was seen in 9 of 16 immunosuppressed rats at 12 weeks. Six animals remained functionally recovered at 14 weeks and contained an average of 5750+/-1450 (SEM) dopaminergic neurons. Between 9 and 14 weeks, three immunosuppressed rats rejected their grafts, based on rotation scores and immunohistochemical demonstration of cell infiltrates. One additional immunosuppressed rat showed evidence of ongoing rejection at 14 weeks. The striata in animals with ongoing or recent rejection contained large numbers of CD4- and CD8-positive lymphocytes, NK cells, macrophages, and microglia cells, whereas scar tissue was found in rats with grafts rejected at earlier time points (n = 11). Embryonic porcine ventral mesencephalic tissue matures in the adult rat striatum, reinnervates the host brain, and restores behavioral defects. Immunosuppressive treatment was necessary for long-term graft survival and functional recovery, but did not sufficiently protect from rejection mechanisms. Porcine neural tissue is an interesting alternative to embryonic human tissue for intracerebral transplantation in neurodegenerative diseases. However, to achieve stable graft survival in discordant xenogeneic combinations, an appropriate immunosuppressive treatment or donor tissue modifications are needed.

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keywords
Animals, Behavior, Animal, Brain Tissue Transplantation, Corpus Striatum, Female, Fetal Tissue Transplantation, Graft Rejection, Graft Survival, Humans, Mesencephalon, Parkinsonian Disorders, Pregnancy, Rats, Rats, Sprague-Dawley, Swine, Transplantation, Heterologous, Journal Article, Research Support, Non-U.S. Gov't
in
Cell Transplantation
volume
9
issue
2
pages
12 pages
publisher
Cognizant Communication Corporation
external identifiers
  • scopus:0034101024
ISSN
0963-6897
language
English
LU publication?
yes
id
9ddc995c-0173-46bc-a032-352ca8a834bf
date added to LUP
2017-04-19 18:20:59
date last changed
2017-04-28 11:00:21
@article{9ddc995c-0173-46bc-a032-352ca8a834bf,
  abstract     = {<p>Transplantation of neural tissue from other species has the potential to improve function in patients with neurodegenerative disorders. We investigated the functional effects of embryonic porcine dopaminergic neurons transplanted in a rat model of Parkinson's disease and the immune responses to the grafts in immunosuppressed and nonimmunosuppressed hosts. Twenty-three rats with unilateral 6-hydroxydopamine lesions received dissociated, 27-day-old embryonic porcine ventral mesencephalic tissue in the right striatum. Eighteen rats received cyclosporine (10 mg/kg, IP, daily) during the whole period of 14 weeks, in combination with prednisolone (20 mg/kg, IP, daily) the first 4 days. Five rats served as nonimmunosuppressed controls. All rats were tested for amphetamine-induced rotational behavior at 3-week intervals. Two immunosuppressed rats were excluded due to severe side effects of the treatment. Functional recovery was seen in 9 of 16 immunosuppressed rats at 12 weeks. Six animals remained functionally recovered at 14 weeks and contained an average of 5750+/-1450 (SEM) dopaminergic neurons. Between 9 and 14 weeks, three immunosuppressed rats rejected their grafts, based on rotation scores and immunohistochemical demonstration of cell infiltrates. One additional immunosuppressed rat showed evidence of ongoing rejection at 14 weeks. The striata in animals with ongoing or recent rejection contained large numbers of CD4- and CD8-positive lymphocytes, NK cells, macrophages, and microglia cells, whereas scar tissue was found in rats with grafts rejected at earlier time points (n = 11). Embryonic porcine ventral mesencephalic tissue matures in the adult rat striatum, reinnervates the host brain, and restores behavioral defects. Immunosuppressive treatment was necessary for long-term graft survival and functional recovery, but did not sufficiently protect from rejection mechanisms. Porcine neural tissue is an interesting alternative to embryonic human tissue for intracerebral transplantation in neurodegenerative diseases. However, to achieve stable graft survival in discordant xenogeneic combinations, an appropriate immunosuppressive treatment or donor tissue modifications are needed.</p>},
  author       = {Larsson, L C and Czech, K A and Brundin, P and Widner, H},
  issn         = {0963-6897},
  keyword      = {Animals,Behavior, Animal,Brain Tissue Transplantation,Corpus Striatum,Female,Fetal Tissue Transplantation,Graft Rejection,Graft Survival,Humans,Mesencephalon,Parkinsonian Disorders,Pregnancy,Rats,Rats, Sprague-Dawley,Swine,Transplantation, Heterologous,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  month        = {05},
  number       = {2},
  pages        = {72--261},
  publisher    = {Cognizant Communication Corporation},
  series       = {Cell Transplantation},
  title        = {Intrastriatal ventral mesencephalic xenografts of porcine tissue in rats : immune responses and functional effects},
  volume       = {9},
  year         = {2000},
}