Abstract
Successful transplantation of conventional tissues between individuals requires matching of human leukocyte associated antigens (HLA), in order to prevent rejection. Although the same principles apply to tissues differentiated from embryonic stem (ES) cells, recent advances in gene delivery and genetic regulation have raised the prospect of engineering grafts with reduced levels of HLA expression. This strategy may mitigate the effects of extensive HLA polymorphism which restricts the availability of suitable donors and necessitates the maintenance of large donor registries. Here, we discuss the potential of employing RNA interference (RNAi) to knockdown HLA expression, enabling allogeneic cells to evade immune recognition. We discuss how lentivirus-mediated delivery of short hairpin RNAs (shRNA) targeting pan-class I and allele-specific HLA achieves efficient, dose- dependent reduction in surface HLA expression in human cells. Thus, by combining genetic engineering and regenerative medicine, RNAi-induced silencing of HLA expression has the potential to create histocompatibility-enhanced and, perhaps even, "universally" compatible cellular grafts.
| Original language | English (US) |
|---|---|
| Title of host publication | The Immunological Barriers to Regenerative Medicine |
| Publisher | Springer New York |
| Pages | 147-173 |
| Number of pages | 27 |
| ISBN (Electronic) | 9781461454809 |
| ISBN (Print) | 9781461454793 |
| DOIs | |
| State | Published - Jan 1 2013 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
Prospects for designing 'universal' stem cell lines. / Cicciarelli, James C.; Lemp, Nathan A.; Kasahara, Noriyuki.
The Immunological Barriers to Regenerative Medicine. Springer New York, 2013. p. 147-173.Research output: Chapter in Book/Report/Conference proceeding › Chapter
}
TY - CHAP
T1 - Prospects for designing 'universal' stem cell lines
AU - Cicciarelli, James C.
AU - Lemp, Nathan A.
AU - Kasahara, Noriyuki
PY - 2013/1/1
Y1 - 2013/1/1
N2 - Successful transplantation of conventional tissues between individuals requires matching of human leukocyte associated antigens (HLA), in order to prevent rejection. Although the same principles apply to tissues differentiated from embryonic stem (ES) cells, recent advances in gene delivery and genetic regulation have raised the prospect of engineering grafts with reduced levels of HLA expression. This strategy may mitigate the effects of extensive HLA polymorphism which restricts the availability of suitable donors and necessitates the maintenance of large donor registries. Here, we discuss the potential of employing RNA interference (RNAi) to knockdown HLA expression, enabling allogeneic cells to evade immune recognition. We discuss how lentivirus-mediated delivery of short hairpin RNAs (shRNA) targeting pan-class I and allele-specific HLA achieves efficient, dose- dependent reduction in surface HLA expression in human cells. Thus, by combining genetic engineering and regenerative medicine, RNAi-induced silencing of HLA expression has the potential to create histocompatibility-enhanced and, perhaps even, "universally" compatible cellular grafts.
AB - Successful transplantation of conventional tissues between individuals requires matching of human leukocyte associated antigens (HLA), in order to prevent rejection. Although the same principles apply to tissues differentiated from embryonic stem (ES) cells, recent advances in gene delivery and genetic regulation have raised the prospect of engineering grafts with reduced levels of HLA expression. This strategy may mitigate the effects of extensive HLA polymorphism which restricts the availability of suitable donors and necessitates the maintenance of large donor registries. Here, we discuss the potential of employing RNA interference (RNAi) to knockdown HLA expression, enabling allogeneic cells to evade immune recognition. We discuss how lentivirus-mediated delivery of short hairpin RNAs (shRNA) targeting pan-class I and allele-specific HLA achieves efficient, dose- dependent reduction in surface HLA expression in human cells. Thus, by combining genetic engineering and regenerative medicine, RNAi-induced silencing of HLA expression has the potential to create histocompatibility-enhanced and, perhaps even, "universally" compatible cellular grafts.
UR - http://www.scopus.com/inward/record.url?scp=84905717841&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84905717841&partnerID=8YFLogxK
U2 - 10.1007/978-1-4614-5480-9_9
DO - 10.1007/978-1-4614-5480-9_9
M3 - Chapter
SN - 9781461454793
SP - 147
EP - 173
BT - The Immunological Barriers to Regenerative Medicine
PB - Springer New York
ER -