Autologous blood cell therapies from pluripotent stem cells

Abstract

The discovery of human embryonic stem cells (hESCs) raised promises for a universal resource for cell based therapies in regenerative medicine. Recently, fast-paced progress has been made towards the generation of pluripotent stem cells (PSCs) amenable for clinical applications, culminating in reprogramming of adult somatic cells to autologous PSCs that can be indefinitely expanded in vitro. However, besides the efficient generation of bona fide, clinically safe PSCs (e.g., without the use of oncoproteins and gene transfer based on viruses inserting randomly into the genome), a major challenge in the field remains how to efficiently differentiate PSCs to specific lineages and how to select cells that will function normally upon transplantation in adults. In this review, we analyse the in vitro differentiation potential of PSCs to the hematopoietic lineage by discussing blood cell types that can be currently obtained, limitations in derivation of adult-type HSCs and prospects for clinical application of PSCs-derived blood cells.

Figure 1. Blood cells from pluripotent stem cells

Mouse ES cells expressing ectopic HoxB4 differentiate on OP9 stroma into repopulating HSC (A: hematopoietic cells from day 6 embryoid body-derived cells after seven days of co-culture with OP9 stroma). Human iPS cells readily give rise to multiple blood cells including erythroid progenitors, yet have not yet been efficiently differentiated into HSC (B: BFU-E colony emerging from embryoid body-derived cells plated in methylcellulose supplemented with hematopoietic cytokines). Abbreviations: BFU-E (burst forming colony-erythroid); ES (embryonic stem); HSC (hematopoietic stem cells); iPS (induced pluripotent stem); OP9 (murine M-CSF-/- stromal line).