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Effects of immunosuppressive treatment on host responses against intracerebral porcine neural tissue xenografts in rats

Wennberg, Lars; Czech, Kimberly A.; Larsson, L C LU ; Mirza, B LU ; Bennet, William; Song, Z and Widner, Håkan LU (2001) In Transplantation 71(12). p.806-1797
Abstract

BACKGROUND: Embryonic xenogeneic neural tissue is an alternative for transplantation in Parkinson's disease, but immune responses limit the application. The aims of this study were to enhance the in vitro viability rates by donor tissue pretreatment; to compare the efficacy of cyclosporine A (CsA) and tacrolimus (FK) in inhibiting xenograft rejection in rats; to evaluate additional inductive therapy with prednisolone (PRE) or mycophenolate mofetil (MMF).

METHODS: Tirilazad (a lipid peroxidase inhibitor) or FK and acYVAD-cmk (a caspase inhibitor), were added to embryonic porcine ventral mesencephalic tissue and viability was assessed in vitro. Tirilazad-treated tissue was grafted to the striatum of rats that were either left... (More)

BACKGROUND: Embryonic xenogeneic neural tissue is an alternative for transplantation in Parkinson's disease, but immune responses limit the application. The aims of this study were to enhance the in vitro viability rates by donor tissue pretreatment; to compare the efficacy of cyclosporine A (CsA) and tacrolimus (FK) in inhibiting xenograft rejection in rats; to evaluate additional inductive therapy with prednisolone (PRE) or mycophenolate mofetil (MMF).

METHODS: Tirilazad (a lipid peroxidase inhibitor) or FK and acYVAD-cmk (a caspase inhibitor), were added to embryonic porcine ventral mesencephalic tissue and viability was assessed in vitro. Tirilazad-treated tissue was grafted to the striatum of rats that were either left untreated or immunosuppressed with FK (1 mg/kg) or CsA (15 mg/kg) alone or in combination with a 2-week PRE (20 mg/kg) or MMF (40 mg/kg) induction course. Xenograft survival and host responses were determined using immunohistochemistry.

RESULTS: Pretreatment with tirilazad enhanced tissue survival in vitro. After transplantation into untreated controls, there was no graft survival at twelve weeks. Neural cell counts were significantly improved in immunosuppressed recipients, but there were no differences between the treatment groups. Additional inductive treatment reduced the infiltration with CD4+ and CD8+ cells, and macrophage infiltration was reduced compared with animals given CsA or FK alone.

CONCLUSION: Pretreatment of the donor tissue with free-radical scavengers reduces cell loss caused by tissue trauma. Porcine neural tissue xenografts survive significantly better in animals immunosuppressed with either FK or CsA. Additional inductive treatment with PRE or MMF reduced the infiltration of host cells into the xenografts.

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keywords
Animals, Antibody Formation, Body Weight, Brain, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cell Count, Drug Therapy, Combination, Fetal Tissue Transplantation, Graft Survival, Immunosuppressive Agents, Lipid Peroxidation, Macrophages, Male, Mice, Mice, Nude, Nerve Tissue, Neurons, Neuroprotective Agents, Pregnatrienes, Preservation, Biological, Rats, Rats, Inbred Lew, Survival Analysis, Swine, Transplantation, Heterologous, Journal Article, Research Support, Non-U.S. Gov't
in
Transplantation
volume
71
issue
12
pages
10 pages
publisher
Lippincott Williams & Wilkins
external identifiers
  • scopus:0035958192
ISSN
0041-1337
language
English
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yes
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95322452-518a-4238-b1ee-a634afa4de0e
date added to LUP
2017-04-19 18:18:33
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2018-01-07 11:59:52
@article{95322452-518a-4238-b1ee-a634afa4de0e,
  abstract     = {<p>BACKGROUND: Embryonic xenogeneic neural tissue is an alternative for transplantation in Parkinson's disease, but immune responses limit the application. The aims of this study were to enhance the in vitro viability rates by donor tissue pretreatment; to compare the efficacy of cyclosporine A (CsA) and tacrolimus (FK) in inhibiting xenograft rejection in rats; to evaluate additional inductive therapy with prednisolone (PRE) or mycophenolate mofetil (MMF).</p><p>METHODS: Tirilazad (a lipid peroxidase inhibitor) or FK and acYVAD-cmk (a caspase inhibitor), were added to embryonic porcine ventral mesencephalic tissue and viability was assessed in vitro. Tirilazad-treated tissue was grafted to the striatum of rats that were either left untreated or immunosuppressed with FK (1 mg/kg) or CsA (15 mg/kg) alone or in combination with a 2-week PRE (20 mg/kg) or MMF (40 mg/kg) induction course. Xenograft survival and host responses were determined using immunohistochemistry.</p><p>RESULTS: Pretreatment with tirilazad enhanced tissue survival in vitro. After transplantation into untreated controls, there was no graft survival at twelve weeks. Neural cell counts were significantly improved in immunosuppressed recipients, but there were no differences between the treatment groups. Additional inductive treatment reduced the infiltration with CD4+ and CD8+ cells, and macrophage infiltration was reduced compared with animals given CsA or FK alone.</p><p>CONCLUSION: Pretreatment of the donor tissue with free-radical scavengers reduces cell loss caused by tissue trauma. Porcine neural tissue xenografts survive significantly better in animals immunosuppressed with either FK or CsA. Additional inductive treatment with PRE or MMF reduced the infiltration of host cells into the xenografts.</p>},
  author       = {Wennberg, Lars and Czech, Kimberly A. and Larsson, L C and Mirza, B and Bennet, William and Song, Z and Widner, Håkan},
  issn         = {0041-1337},
  keyword      = {Animals,Antibody Formation,Body Weight,Brain,CD4-Positive T-Lymphocytes,CD8-Positive T-Lymphocytes,Cell Count,Drug Therapy, Combination,Fetal Tissue Transplantation,Graft Survival,Immunosuppressive Agents,Lipid Peroxidation,Macrophages,Male,Mice,Mice, Nude,Nerve Tissue,Neurons,Neuroprotective Agents,Pregnatrienes,Preservation, Biological,Rats,Rats, Inbred Lew,Survival Analysis,Swine,Transplantation, Heterologous,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  month        = {06},
  number       = {12},
  pages        = {806--1797},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {Transplantation},
  title        = {Effects of immunosuppressive treatment on host responses against intracerebral porcine neural tissue xenografts in rats},
  volume       = {71},
  year         = {2001},
}