Generation of T lineage cells from human embryonic stem cells in a feeder free system.
Human embryonic stem cells (hESC) have the potential to revolutionize certain medical treatments, including T-cell-based therapies. However, optimal approaches to develop T cells from hESC are lacking. In this report, we show that T-cell progenitors can be derived from hESC cultured as embryoid bodies (EBs). These EB-derived T-cell progenitors give rise to phenotypically and functionally normal cells of the T lineage when transferred into human thymic tissue implanted in immunocompromised mice, suggesting that introduction of these progenitors into patients may also yield functional T cells. Moreover, hematopoietic progenitors demonstrating T-cell potential appeared to be CD45+/CD34+, resembling those found in normal bone marrow. In contrast to T cells developed from hESC cocultured on murine stromal cells, the EB-derived T cells also expressed normal levels of CD45. Importantly, the EB system eliminates the previous need for murine cocultures, a key impediment to developing a protocol for T-cell progenitor derivation suitable for clinical use. Furthermore, following lentiviral-mediated introduction of a vector expressing enhanced green fluorescent protein into hESC, stable transgene expression was maintained throughout differentiation, suggesting a potential for gene therapy approaches aimed at the augmentation of T-cell function or treatment of T-cell disorders.
Galić
Zoran
Z
Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, 90095, USA. zgalic@ucla.edu
Kitchen
Scott G
SG
Subramanian
Aparna
A
Bristol
Greg
G
Marsden
Matthew D
MD
Balamurugan
Arumugam
A
Kacena
Amelia
A
Yang
Otto
O
Zack
Jerome A
JA
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage; D004622:Embryo, Mammalian / Q000166:cytology; D053595:Embryonic Stem Cells / Q000166:cytology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006410:Hematopoiesis; D006801:Humans; D007700:Kinetics; D051379:Mice; D010641:Phenotype; D013601:T-Lymphocytes / Q000166:cytology*
C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins