Survival and immunogenicity of mesenchymal stem cells from the green fluorescent protein transgenic rat in the adult rat brain.
BACKGROUND
A major technical limitation in preclinical cell replacement research is the ability to discriminate between donor and host tissue after transplantation. This problem has been lessened by the availability of transgenic animals that express "reporter" genes, such as green fluorescent protein (GFP).


OBJECTIVE
We determined the usefulness of one such transgenic reporter rat to assess the survival of bone marrow-derived rat mesenchymal stem cells (MSCs) following direct transplantation into the intact adult brain. We also sought to determine if the expression of GFP in the brain affected the survival of the MSCs or the host's neuroimmune response to the cells.


METHODS
Rats received intrastriatal injections of sterile transplantation medium, 100 000 normal MSCs, or 100 000 GFP-MSCs and were killed humanely 1, 4, 7, 28, and 42 days posttransplantation for astrocyte and microglial immunohistochemical staining.


RESULTS
GFP-MSCs were evident at each examination, although their survival declined over time. Graft volume estimates comparing normal and GFP-MSCs revealed that GFP expression did not adversely affect the survival of the stem cells in the brain. Furthermore, immunostaining for astrocytes and microglia revealed that expression of the reporter protein did not affect the immunogenicity of the stem cells.


CONCLUSIONS
These data indicate the usefulness of GFP for investigating the survival of MSCs following transplantation to the brain. However, the mechanisms responsible for the poor survival of the stem cells must be elucidated if these cells are to serve cell-based therapies for neurodegenerative disorders.
Moloney
Teresa C
TC
National University of Ireland, Galway, Ireland.
Dockery
Peter
P
Windebank
Anthony J
AJ
Barry
Frank P
FP
Howard
Linda
L
Dowd
Eilís
E
D000818:Animals; D001927:Brain Diseases / Q000601:surgery*; D002478:Cells, Cultured; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006085:Graft Survival / Q000235:genetics / Q000276:immunology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000276:immunology*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic
D049452:Green Fluorescent Proteins