Prospects for designing 'universal' stem cell lines

James C. Cicciarelli, Nathan A. Lemp, Noriyuki Kasahara

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Scopus citations

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 languageEnglish (US)
Title of host publicationThe Immunological Barriers to Regenerative Medicine
PublisherSpringer New York
Pages147-173
Number of pages27
ISBN (Electronic)9781461454809
ISBN (Print)9781461454793
DOIs
StatePublished - Jan 1 2013
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Cicciarelli, J. C., Lemp, N. A., & Kasahara, N. (2013). Prospects for designing 'universal' stem cell lines. In The Immunological Barriers to Regenerative Medicine (pp. 147-173). Springer New York. https://doi.org/10.1007/978-1-4614-5480-9_9