Bart Vandekerckhove, Stijn Vanhee, Stefanie Van Coppernolle, Sylvia Snauwaert, Imke Velghe, Tom Taghon, Georges Leclercq, Tessa Kerre, Jean Plum

Department of Clinical Chemistry, Microbiology and Immunology, University of Ghent, Belgium

TABLE OF CONTENTS

1. Abstract

2. Introduction

3. Generation of HPC/HSC from hESC

3.1. Generation of HSC in the embryo

3.2. Generation of HSC/HPC from hESC

3.3. Characterization of HPC/HSC

3.4. SCID repopulating cells (SRC)

4. Generation of lymphoid cells from HPC/HSC

4.1. Generation of B cells

4.2. Generation of NK cells

4.3. Generation of T cells

5. The quality of the T cell repertoire

5.1. CD4/CD8-polyclonality

5.2. Positive selection

5.3. Negative selection

6. Generation of autologous lymphocytes from hiPSC

7. Conclusions

8. Acknowledgement

9. References

1. ABSTRACT

Stem cell transplant recipients and acquired or inherited immune-deficiency patients could benefit from the infusion of B, T and/or NK cells. These lymphoid cells can be generated in vitro from bone marrow derived CD34⁺CD45⁺ hematopoietic stem cells (HSC). The number of cells that can be obtained in this way is limited especially in the adult. An alternative source may therefore constitute human pluripotent stem cells (PSC) such as embryonic (hESC) or induced pluripotent stem cells (hiPSC). Here, we focus on present knowledge on the generation of lymphoid cells from hESC. The two main obstacles for the generation of clinically relevant immune cells are the failure to generate from hESC long-term repopulating HSC which could be kept in culture for prolonged time; and insufficient knowledge of the selection process which generates mature T cells from CD4 CD8 double positive (DP) precursors in vitro.