Concise Review: Recent Advances in the In Vitro Derivation of Blood Cell Populations

Abstract

Hematopoietic cell-based therapies are currently available treatment options for many hematological and nonhematological disorders. However, the scarcity of allogeneic donor-derived cells is a major hurdle in treating these disorders. Embryonic stem cell-based directed differentiation and direct reprogramming of somatic cells provide excellent tools for the potential generation of hematopoietic stem cells usable in the clinic for cellular therapies. In addition to blood stem cell transplantation, mature blood cells such as red blood cells, platelets, and engineered T cells have also been increasingly used to treat several diseases. Besides cellular therapies, induced blood progenitor cells generated from autologous sources (either induced pluripotent stem cells or somatic cells) can be useful for disease modeling of bone marrow failures and acquired blood disorders. However, although great progress has been made toward these goals, we are still far from the use of in vitro-derived blood products in the clinic. We review the current state of knowledge on the directed differentiation of embryonic stem cells and the reprogramming of somatic cells toward the generation of blood stem cells and derivatives. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:1330-1337 SIGNIFICANCEHematopoietic cell-based therapies are currently available treatment options for many hematological and nonhematological disorders. However, the scarcity of allogeneic donor-derived cells is a major hurdle in treating these disorders. The current state of knowledge on the directed differentiation of embryonic stem cells and the reprogramming of somatic cells toward the generation of blood stem cells and derivatives is reviewed.

Protein arginine methyltransferase 6 controls erythroid gene expression and differentiation of human CD34+ progenitor cells

“…Significant efforts are being made worldwide to develop efficient in vitro protocols for the production of therapeutic cells from hematopoietic or embryonic stem cells. 57 Epigenetic compounds, which target epigenetic factors, such as PRMT6, could contribute to more effective in vitro differentiation in the future.…”

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] .…”

The role of Wnt signaling in hematopoietic stem cell development

“…The first phase, termed primitive, produces mostly erythrocytes and macrophages that transiently sustain the organism during early development. These cell types arise in the yolk sac in mammals and in the intermediate cell mass/cephalic mesoderm in the zebrafish (reviewed in Davidson and Zon 2004, and Batta et al 2016). In the zebrafish, these waves are temporally and spatially distinct from the definitive waves of hematopoiesis, which give rise first to committed erythromyeloid precursors (EMPs) in the posterior blood island then to HSCs that appear along the floor of the dorsal aorta.…”