Toward clinical therapies using hematopoietic cells derived from human pluripotent stem cells

Abstract

Human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) provide remarkable cellular platforms to better understand human hematopoiesis and to develop clinically applicable hematopoietic cell-based therapies. Over the past decade, hESCs have been used to characterize molecular and cellular mechanisms underpinning the differentiation of hematopoietic progenitors and mature, functional hematopoietic cells. These advances are now poised to lead to clinical translation of hESC- and iPSC-derived hematopoietic cells for novel therapies in the next few years. On the basis of areas of recent success, initial clinical use of hematopoietic cells derived from human pluripotent stem cells will probably be in the areas of transfusion therapies (erythrocytes and platelets) and immune therapies (natural killer cells). In contrast, efficient development and isolation of hematopoietic stem cells capable of long-term, multilineage engraftment still remains a significant challenge. Technical, safety, and regulatory concerns related to clinical applications of human PSCs must be appropriately addressed. However, proper consideration of these issues should facilitate and not inhibit clinical translation of new therapies. This review outlines the current status of hematopoietic cell development and what obstacles must be surmounted to bring hematopoietic cell therapies from human PSCs from "bench to bedside."

Figure 1

Derivation of hematopoietic cells from hESCs suitable for clinic therapies. Both hESCs derived from preimplantation blastocysts and iPSCs produced from somatic cells by gene transfer and/or chemical treatment can be used to investigate blood cell development. Two main methods have been used to produce hematopoietic cells from hESCs and iPSCs: embryoid body formation and stromal cell coculture. In vitro and in vivo studies have shown the development of essentially all mature hematopoietic cell populations from hESCs, with similar studies using human iPSCs being under way. The boxes around RBCs, platelets, and NK cells suggest these to be the most promising cell lineages to take into clinical trials, based on current status of the field.

Figure 2

Hurdles to overcome for clinical translation of hPSC-derived therapies. Although novel therapies starting from hPSCs are an enticing prospect, multiple technical, safety, and regulatory hurdles outlined in this figure and the text will need to be surmounted for successful clinical translation. It is essential that, although regulatory and other nonscientific interests should be considered and appropriately accommodated, these considerations should facilitate and not inhibit clinical translation of hPSCs as these therapies move to the clinic.