Making a Hematopoietic Stem Cell

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.

TrendsMany reprogramming strategies attempt to derive hematopoietic stem and progenitor cells (HSPCs) de novo from pluripotent stem cells (PSCs) or somatic cells. Each strategy yields hematopoietic cells of varying functionality.The in vivo or in vitro niche, cytokine supplementation, and culture media greatly influence reprogramming efficiency. Incorporating these elements into a finalized reprogramming protocol is crucial to generate bona fide HSCs.Some reprogramming strategies recapitulate developmental hematopoiesis ‘in a dish’. This allows us to study blood development in vitro as well as the pathways involved in hematologic disease.Once perfected, HSPC reprogramming protocols will be used for hematologic disease modeling and drug discovery. Also, patient-specific HSPC transplant will circumvent the risk of graft-versus-host disease and other immunological complications.