Emerging concepts for the in vitro derivation of murine haematopoietic stem and progenitor cells

Abstract

Well into the second decade of the 21st century, the field of regenerative medicine is bursting with hopes and promises to heal young and old. The bespoken generation of cells is thought to offer unprecedented cures for a vast range of diseases. Haematological disorders have already benefited tremendously from stem cell therapy in the form of bone marrow transplantation. However, lack of compatible donors often means that patients remain on transplantation waiting lists for too long. The in vitro derivation of haematopoietic stem cells offers the possibility to generate tailor-made cells for the treatment of these patients. Promising approaches to generate in vitro-derived blood progenitors include the directed differentiation of pluripotent stem cells and the reprogramming of somatic cells.

Hemangioblast, hemogenic endothelium, and primitive versus definitive hematopoiesis

“…One might ask why it is so important to have a clear understanding and definition of primitive versus definitive or successive waves of blood emergence during the in vitro differentiation process. A long-standing quest in the field of ESC differentiation to blood has been the in vitro generation of HSCs 21,22 . In keeping with embryonic development, it has been proposed that in vitro hematopoietic differentiation also occurred in sequential steps with a primitive wave followed by a definitive wave and the production of HSCs [23][24][25] .…”

Shedding light on hematopoietic stem cells: formation, regulation, and utilization

“…The fourth topic covers the recent progresses and future prospects for in vitro HSC production. The generation of tailor‐made HSCs in vitro via directed differentiation of pluripotent stem cells (e.g. ES cells, iPS cells), or the reprogramming of somatic cells , represents the Holy Grail since decades.…”

Transcriptional control of blood cell emergence

“…It is thought that mastering the de novo generation of HSPCs from unlimited cell sources (somatic or pluripotent) will provide tailormade cell populations usable in the clinic to cure a large range of haematological and autoimmune diseases [102,103]. It is thought that mastering the de novo generation of HSPCs from unlimited cell sources (somatic or pluripotent) will provide tailormade cell populations usable in the clinic to cure a large range of haematological and autoimmune diseases [102,103].…”

“…Understanding the transcriptional network that leads to the formation of haematopoietic stem and progenitor cells (HSPCs) should provide the critical knowledge required for generating these cells via reprogramming or forward programming. It is thought that mastering the de novo generation of HSPCs from unlimited cell sources (somatic or pluripotent) will provide tailormade cell populations usable in the clinic to cure a large range of haematological and autoimmune diseases [102,103]. Many studies have explored the reprograming of somatic cells to blood cells using a variety of transcription factors (Table 1) [104][105][106][107][108][109][110][111][112].…”