Survival of neural progenitors allografted into the CNS of immunocompetent recipients is highly dependent on transplantation site

Miroslaw Janowski, C. Engels, M. Gorelik, A. Lyczek, S. Bernard, Jeff W Bulte, Piotr Walczak

Research output: Contribution to journalArticle

Abstract

Allografts continue to be used in clinical neurotransplantation studies; hence, it is crucial to understand the mechanisms that govern allograft tolerance. We investigated the impact of transplantation site within the brain on graft survival. Mouse [Friend leukemia virus, strain B (FVB)] glial precursors, transfected with luciferase, were injected (3 × 105) into the forceps minor (FM) or striatum (STR). Immunodeficient rag2-/- and immunocompetent BALB/c mice were used as recipients. Magnetic resonance imaging (MRI) confirmed that cells were precisely deposited at the selected coordinates. The graft viability was assessed noninvasively with bioluminescent imaging (BLI) for a period of 16 days. Regardless of implantation site, all grafts (n = 10) deposited in immunodeficient animals revealed excellent survival. In contrast, immunocompetent animals only accepted grafts at the STR site (n = 10), whereas all the FM grafts were rejected (n = 10). To investigate the factors that led to rejection of FM grafts, with acceptance of STR grafts, another group of animals (n = 19) was sacrificed during the prerejection period, on day 5. Near-infrared fluorescence imaging with IRDye 800CW-polyethylene glycol probe displayed similar blood-brain barrier disruption at both graft locations. The morphological distribution of FM grafts was cylindrical, parallel to the needle track, whereas cells transplanted into the STR accumulated along the border between the STR and the corpus callosum. There was significantly less infiltration by both innate and adaptive immune cells in the STR grafts, especially along the calloso-striatal border. With allograft survival being dependent on the transplantation site, the anatomical coordinates of the graft target should always be taken into account as it may determine the success or failure of therapy.

Original languageEnglish (US)
Pages (from-to)253-262
Number of pages10
JournalCell Transplantation
Volume23
Issue number2
DOIs
StatePublished - Feb 2014

Fingerprint

Grafts
Transplantation
Transplants
Surgical Instruments
Transplantation (surgical)
Animals
Allografts
Friend murine leukemia virus
Transplantation Tolerance
Corpus Striatum
Murine Leukemia Viruses
Imaging techniques
Corpus Callosum
Optical Imaging
Graft Survival
Blood-Brain Barrier
Luciferases
Neuroglia
Viruses
Needles

Keywords

  • Brain
  • Glial progenitors
  • Rejection
  • Stem cells
  • Transplantation

ASJC Scopus subject areas

  • Cell Biology
  • Transplantation
  • Biomedical Engineering

Cite this

Survival of neural progenitors allografted into the CNS of immunocompetent recipients is highly dependent on transplantation site. / Janowski, Miroslaw; Engels, C.; Gorelik, M.; Lyczek, A.; Bernard, S.; Bulte, Jeff W; Walczak, Piotr.

In: Cell Transplantation, Vol. 23, No. 2, 02.2014, p. 253-262.

Research output: Contribution to journalArticle

@article{b440c1b28d4f4948a7e74ed53739fd23,
title = "Survival of neural progenitors allografted into the CNS of immunocompetent recipients is highly dependent on transplantation site",
abstract = "Allografts continue to be used in clinical neurotransplantation studies; hence, it is crucial to understand the mechanisms that govern allograft tolerance. We investigated the impact of transplantation site within the brain on graft survival. Mouse [Friend leukemia virus, strain B (FVB)] glial precursors, transfected with luciferase, were injected (3 × 105) into the forceps minor (FM) or striatum (STR). Immunodeficient rag2-/- and immunocompetent BALB/c mice were used as recipients. Magnetic resonance imaging (MRI) confirmed that cells were precisely deposited at the selected coordinates. The graft viability was assessed noninvasively with bioluminescent imaging (BLI) for a period of 16 days. Regardless of implantation site, all grafts (n = 10) deposited in immunodeficient animals revealed excellent survival. In contrast, immunocompetent animals only accepted grafts at the STR site (n = 10), whereas all the FM grafts were rejected (n = 10). To investigate the factors that led to rejection of FM grafts, with acceptance of STR grafts, another group of animals (n = 19) was sacrificed during the prerejection period, on day 5. Near-infrared fluorescence imaging with IRDye 800CW-polyethylene glycol probe displayed similar blood-brain barrier disruption at both graft locations. The morphological distribution of FM grafts was cylindrical, parallel to the needle track, whereas cells transplanted into the STR accumulated along the border between the STR and the corpus callosum. There was significantly less infiltration by both innate and adaptive immune cells in the STR grafts, especially along the calloso-striatal border. With allograft survival being dependent on the transplantation site, the anatomical coordinates of the graft target should always be taken into account as it may determine the success or failure of therapy.",
keywords = "Brain, Glial progenitors, Rejection, Stem cells, Transplantation",
author = "Miroslaw Janowski and C. Engels and M. Gorelik and A. Lyczek and S. Bernard and Bulte, {Jeff W} and Piotr Walczak",
year = "2014",
month = "2",
doi = "10.3727/096368912X661328",
language = "English (US)",
volume = "23",
pages = "253--262",
journal = "Cell Transplantation",
issn = "0963-6897",
publisher = "Cognizant Communication Corporation",
number = "2",

}

TY - JOUR

T1 - Survival of neural progenitors allografted into the CNS of immunocompetent recipients is highly dependent on transplantation site

AU - Janowski, Miroslaw

AU - Engels, C.

AU - Gorelik, M.

AU - Lyczek, A.

AU - Bernard, S.

AU - Bulte, Jeff W

AU - Walczak, Piotr

PY - 2014/2

Y1 - 2014/2

N2 - Allografts continue to be used in clinical neurotransplantation studies; hence, it is crucial to understand the mechanisms that govern allograft tolerance. We investigated the impact of transplantation site within the brain on graft survival. Mouse [Friend leukemia virus, strain B (FVB)] glial precursors, transfected with luciferase, were injected (3 × 105) into the forceps minor (FM) or striatum (STR). Immunodeficient rag2-/- and immunocompetent BALB/c mice were used as recipients. Magnetic resonance imaging (MRI) confirmed that cells were precisely deposited at the selected coordinates. The graft viability was assessed noninvasively with bioluminescent imaging (BLI) for a period of 16 days. Regardless of implantation site, all grafts (n = 10) deposited in immunodeficient animals revealed excellent survival. In contrast, immunocompetent animals only accepted grafts at the STR site (n = 10), whereas all the FM grafts were rejected (n = 10). To investigate the factors that led to rejection of FM grafts, with acceptance of STR grafts, another group of animals (n = 19) was sacrificed during the prerejection period, on day 5. Near-infrared fluorescence imaging with IRDye 800CW-polyethylene glycol probe displayed similar blood-brain barrier disruption at both graft locations. The morphological distribution of FM grafts was cylindrical, parallel to the needle track, whereas cells transplanted into the STR accumulated along the border between the STR and the corpus callosum. There was significantly less infiltration by both innate and adaptive immune cells in the STR grafts, especially along the calloso-striatal border. With allograft survival being dependent on the transplantation site, the anatomical coordinates of the graft target should always be taken into account as it may determine the success or failure of therapy.

AB - Allografts continue to be used in clinical neurotransplantation studies; hence, it is crucial to understand the mechanisms that govern allograft tolerance. We investigated the impact of transplantation site within the brain on graft survival. Mouse [Friend leukemia virus, strain B (FVB)] glial precursors, transfected with luciferase, were injected (3 × 105) into the forceps minor (FM) or striatum (STR). Immunodeficient rag2-/- and immunocompetent BALB/c mice were used as recipients. Magnetic resonance imaging (MRI) confirmed that cells were precisely deposited at the selected coordinates. The graft viability was assessed noninvasively with bioluminescent imaging (BLI) for a period of 16 days. Regardless of implantation site, all grafts (n = 10) deposited in immunodeficient animals revealed excellent survival. In contrast, immunocompetent animals only accepted grafts at the STR site (n = 10), whereas all the FM grafts were rejected (n = 10). To investigate the factors that led to rejection of FM grafts, with acceptance of STR grafts, another group of animals (n = 19) was sacrificed during the prerejection period, on day 5. Near-infrared fluorescence imaging with IRDye 800CW-polyethylene glycol probe displayed similar blood-brain barrier disruption at both graft locations. The morphological distribution of FM grafts was cylindrical, parallel to the needle track, whereas cells transplanted into the STR accumulated along the border between the STR and the corpus callosum. There was significantly less infiltration by both innate and adaptive immune cells in the STR grafts, especially along the calloso-striatal border. With allograft survival being dependent on the transplantation site, the anatomical coordinates of the graft target should always be taken into account as it may determine the success or failure of therapy.

KW - Brain

KW - Glial progenitors

KW - Rejection

KW - Stem cells

KW - Transplantation

UR - http://www.scopus.com/inward/record.url?scp=84893276817&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84893276817&partnerID=8YFLogxK

U2 - 10.3727/096368912X661328

DO - 10.3727/096368912X661328

M3 - Article

C2 - 23294627

AN - SCOPUS:84893276817

VL - 23

SP - 253

EP - 262

JO - Cell Transplantation

JF - Cell Transplantation

SN - 0963-6897

IS - 2

ER -