Making a Hematopoietic Stem Cell

Abstract

Previous attempts to either generate or expand hematopoietic stem cells (HSCs) in vitro have involved either ex vivo expansion of pre-existing patient or donor HSCs or de novo generation from pluripotent stem cells (PSCs), comprising both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). iPSCs alleviated ESC ethical issues but attempts to generate functional mature hematopoietic stem and progenitor cells (HSPCs) have been largely unsuccessful. New efforts focus on directly reprogramming somatic cells into definitive HSCs and HSPCs. To meet clinical needs and to advance drug discovery and stem cell therapy, alternative approaches are necessary. In this review, we synthesize the strategies used and the key findings made in recent years by those trying to make an HSC.

Keywords: hematopoiesis; hematopoietic stem cell; reprogramming; transcription factors.

Figure 1

Patient-Specific Hematopoietic Stem and Progenitor Cell (HSPC) Derivation and Future Studies. This diagram demonstrates the general strategy of most patient-specific cell reprogramming processes and future directions. The ideal strategy is to obtain patient/donor somatic cells and reprogram to the cell type of choice, in this case hematopoietic stem cells (HSCs). These HSCs could then be used in a variety of different studies. These include but are not limited to, gene correcting the derived HSCs (or correcting the genetic defect in the obtained patient cells before reprogramming), transplantation, drug screens to identify novel therapeutics for a variety of diseases, generating patient-specific blood products and studying hematopoiesis in vitro.

Figure 2

Various Strategies to Generate Hematopoietic Stem Cells (HSCs). Several groups have attempted to derive HSCs in many different ways. The major differences among the strategies are the starting cells [embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), fibroblasts, lineage committed blood progenitors, and endothelial cells], the media/culture system the cells are reprogrammed on, and the transcription factor (TF) cocktail that the cells are subjected to. Although all efforts are aimed at getting bona fide HSCs, most of the attempts thus far fall short. The boxes list TFs and they are color coded to the arrow denoting the associated outcome.