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.

Significance: 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. 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.

Keywords: Differentiation; Embryonic stem cells; Hemangioblast; Hematopoietic cells; Hematopoietic stem cells; Reprogramming; Stem cell transplantation.

Figure 1.

The in vitro differentiation of ESCs proceeds in well-defined sequential steps leading to the generation of all hematopoietic lineages. Abbreviation: ESCs, embryonic stem cells.

Figure 2.

List of transcription factors and starting cell types used in different studies to generate HSPCs via direct reprogramming. Abbreviations: CMPs, common myeloid progenitors; ES, embryonic stem cell; HSPCs, hematopoietic stem and progenitor cells.

Figure 3.

Generation of HSPCs via reprogramming somatic cells to iPSCs followed by directed differentiation, directed differentiation of ESCs, or direct reprogramming. Clinical utility of HSPCs and differentiated blood cells, including RBCs, MegK, platelets, Gran, Mac, and Lymph. Abbreviations: ESCs, embryonic stem cells; Gran, granulocytes; HSPCs, hematopoietic stem and progenitor cells; iPSCs, induced pluripotent stem cells; Lymph, lymphocytes; Mac, macrophages; MegK, megakaryocytes; RBCs, red blood cells.