Survival of encapsulated human primary fibroblasts and erythropoietin expression under xenogeneic conditions.

Details

Serval ID
serval:BIB_81DB5DB94455
Type
Article: article from journal or magazin.
Collection
Publications
Title
Survival of encapsulated human primary fibroblasts and erythropoietin expression under xenogeneic conditions.
Journal
Human Gene Therapy
Author(s)
Schwenter F., Schneider B.L., Pralong W.F., Déglon N., Aebischer P.
ISSN
1043-0342 (Print)
ISSN-L
1043-0342
Publication state
Published
Issued date
2004
Volume
15
Number
7
Pages
669-680
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
Allogeneic cells are the most attractive source for cell transplantation, as the use of xenogeneic cells is hampered by safety concerns and the use of autologous cells involves practical difficulties. The immune rejection of allogeneic cells can be overcome by physical immunoprotection provided by polymer encapsulation. To study the variability of cell and donor sources, we compared different primary human cells as candidates for gene therapy-mediated delivery of human erythropoietin (hEpo). DARC-3.1 fibroblasts, MDX-01 fibroblasts, and ARPE-19 retinal pigment epithelial cells were encapsulated into polyethersulfone hollow fibers and implanted for 1 month in nude mice as well as in immunocompetent and FK506-immunosuppressed mice to test their in vivo resistance, with the assumption that xenogeneic conditions constitute a stringent model for human application. DARC-3.1 fibroblasts showed the best survival, prompting us to evaluate cell lineages from the same donor (DARC-3.2) or another donor (DARC-4.3 and DARC-4.4). With the exception of DARC-4.3, the remaining three lineages showed comparable survival in immunocompetent C3H and DBA/2J mice. DARC-3.1 fibroblasts were retrovirally engineered with hEpo cDNA, reaching a secretion level of 170 IU of hEpo per 10(6) cells per day. Encapsulated DARC-3.1-hEpo cells led to significantly increased hematocrits in the various hosts and under various transplantation conditions. The present study shows that encapsulated primary human DARC-3.1 fibroblasts are able to survive under xenogeneic conditions and, once engineered with hEpo cDNA, to increase the hematocrit of transplanted mice.
Keywords
Animals, Cell Survival, Cell Transplantation/methods, Erythropoietin/analysis, Erythropoietin/biosynthesis, Fibroblasts/cytology, Fibroblasts/metabolism, Hematocrit, Humans, Mice, Mice, Inbred DBA, Polymers/chemistry, Sulfones/chemistry, Transplantation, Heterologous
Pubmed
Web of science
Create date
13/12/2011 17:32
Last modification date
03/03/2018 18:48
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