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Neuroretinal xenotransplantation to immunocompetent hosts in a discordant species combination.

Ghosh, Fredrik LU ; Rauer, Ola LU and Arnér, Karin LU (2008) In Neuroscience 152(Jan 4). p.526-533
Abstract
In spite of its immune privileged state, xenotransplantation within the CNS is associated with rapid graft destruction in immunocompetent hosts. Efforts to enhance graft survival have mostly focused on host immune response, whereas relatively little attention has been paid to donor tissue characteristics. In the present paper, we explore long-term survival of xenogeneic full-thickness neuroretinal transplants in immunocompetent hosts and investigate the significance of tissue integrity in relation to graft survival. Adult rabbits receiving no immunosuppression were used as hosts and fetal Sprague-Dawley rat neuroretina as donors. Using vitreoretinal surgical techniques, rabbits received either a full thickness or a fragmented neuroretinal... (More)
In spite of its immune privileged state, xenotransplantation within the CNS is associated with rapid graft destruction in immunocompetent hosts. Efforts to enhance graft survival have mostly focused on host immune response, whereas relatively little attention has been paid to donor tissue characteristics. In the present paper, we explore long-term survival of xenogeneic full-thickness neuroretinal transplants in immunocompetent hosts and investigate the significance of tissue integrity in relation to graft survival. Adult rabbits receiving no immunosuppression were used as hosts and fetal Sprague-Dawley rat neuroretina as donors. Using vitreoretinal surgical techniques, rabbits received either a full thickness or a fragmented neuroretinal graft to the subretinal space of one eye. Eyes receiving full-thickness grafts were examined morphologically after 91 days and fragmented grafts after 7-14 days. Surviving full thickness grafts were found in six of eight eyes, four of which displayed the normal laminated appearance. Major histocompatibility complex (MHC) up-regulation in surviving grafts was minimal and they contained a well-organized photoreceptor layer, protein kinase C (PKC) labeled rod bipolar cells, parvalbumin labeled AII amacrine cells and glial fibrillary acidic protein (GFAP) labeled Müller cells. Fragmented grafts (n=6) were all destroyed or showed severe signs of rejection. A mass of inflammatory cells derived from the choroid was evident in these specimens, and no labeling of retina-specific cells was seen. We conclude that full-thickness rat neuroretina can survive for several months after subretinal transplantation to the subretinal space of immunocompetent rabbits, while fragmented counterparts are rapidly rejected. Surviving full-thickness grafts can develop many of the normal retinal morphological characteristics, indicating a thriving relationship between the initially immature donor tissue and its foreign host. Our results strongly indicate that donor tissue integrity is a crucial factor for graft survival in CNS xenotransplantation. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
Neuroscience
volume
152
issue
Jan 4
pages
526 - 533
publisher
Elsevier
external identifiers
  • pmid:18280667
  • wos:000254687200026
  • scopus:40849120486
ISSN
1873-7544
DOI
10.1016/j.neuroscience.2007.12.035
language
English
LU publication?
yes
id
d668c3a5-57cb-4394-8143-574a37969a06 (old id 1041833)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18280667?dopt=Abstract
date added to LUP
2008-03-04 11:16:16
date last changed
2017-01-01 07:39:55
@article{d668c3a5-57cb-4394-8143-574a37969a06,
  abstract     = {In spite of its immune privileged state, xenotransplantation within the CNS is associated with rapid graft destruction in immunocompetent hosts. Efforts to enhance graft survival have mostly focused on host immune response, whereas relatively little attention has been paid to donor tissue characteristics. In the present paper, we explore long-term survival of xenogeneic full-thickness neuroretinal transplants in immunocompetent hosts and investigate the significance of tissue integrity in relation to graft survival. Adult rabbits receiving no immunosuppression were used as hosts and fetal Sprague-Dawley rat neuroretina as donors. Using vitreoretinal surgical techniques, rabbits received either a full thickness or a fragmented neuroretinal graft to the subretinal space of one eye. Eyes receiving full-thickness grafts were examined morphologically after 91 days and fragmented grafts after 7-14 days. Surviving full thickness grafts were found in six of eight eyes, four of which displayed the normal laminated appearance. Major histocompatibility complex (MHC) up-regulation in surviving grafts was minimal and they contained a well-organized photoreceptor layer, protein kinase C (PKC) labeled rod bipolar cells, parvalbumin labeled AII amacrine cells and glial fibrillary acidic protein (GFAP) labeled Müller cells. Fragmented grafts (n=6) were all destroyed or showed severe signs of rejection. A mass of inflammatory cells derived from the choroid was evident in these specimens, and no labeling of retina-specific cells was seen. We conclude that full-thickness rat neuroretina can survive for several months after subretinal transplantation to the subretinal space of immunocompetent rabbits, while fragmented counterparts are rapidly rejected. Surviving full-thickness grafts can develop many of the normal retinal morphological characteristics, indicating a thriving relationship between the initially immature donor tissue and its foreign host. Our results strongly indicate that donor tissue integrity is a crucial factor for graft survival in CNS xenotransplantation.},
  author       = {Ghosh, Fredrik and Rauer, Ola and Arnér, Karin},
  issn         = {1873-7544},
  language     = {eng},
  number       = {Jan 4},
  pages        = {526--533},
  publisher    = {Elsevier},
  series       = {Neuroscience},
  title        = {Neuroretinal xenotransplantation to immunocompetent hosts in a discordant species combination.},
  url          = {http://dx.doi.org/10.1016/j.neuroscience.2007.12.035},
  volume       = {152},
  year         = {2008},
}