Mechanistic and Translational Advances Using iPSC-Derived Blood Cells

Abstract

Human induced pluripotent stem cell (iPSC)-based model systems can be used to produce blood cells for the study of both hematologic and non-hematologic disorders. This commentary discusses recent advances that have utilized iPSC-derived red blood cells, megakaryocytes, myeloid cells, and lymphoid cells to model hematopoietic disorders. In addition, we review recent studies that have defined how microglial cells differentiated from iPSC-derived monocytes impact neurodegenerative disease. Related translational insights highlight the utility of iPSC models for studying pathologic anemia, bleeding, thrombosis, autoimmunity, immunodeficiency, blood cancers, and neurodegenerative disease such as Alzheimer’s.

Tropomyosin 1 deficiency facilitates cell state transitions to enhance hemogenic endothelial cell specification during hematopoiesis

“…In vitro-derived blood cells have recently been shown to support the production of clinical testing reagents 44 and cell therapeutics [45][46][47] , but blood cell yields remain inefficient. Factors influencing HE specification have been elusive, but could be co-opted to enhance in vitro hematopoiesis.…”

How Nitric Oxide Hindered the Search for Hemoglobin-Based Oxygen Carriers as Human Blood Substitutes

“…The search for a reliable substitute of blood in the transfusion setting is still ongoing in an exhaustive manner to cover an urgent need in modern society [1]. After dismissing perfluorocarbon-based technology after decades of work [2], and before targeting approaches based on induced pluripotent stem cells that do not yet appear mature for clinical use [3], efforts are presently concentrating in hemoglobin (Hb)-based oxygen (O 2 ) carriers (HBOC). Although HBOCs have been investigated for more than 50 years and several reviews have discussed them as potential candidates [1,[4][5][6][7][8], up to now, no affordable alternatives to allogeneic blood transfusion have yet emerged, at least in acute contexts linked to hemorrhagic shock, where replacing the blood loss without compromising the O 2 carrying function is the primary goal [9].…”

Erythropoietic properties of human induced pluripotent stem cells‐derived red blood cells in immunodeficient mice

“…Human induced pluripotent stem cells (iPSC) can be produced by reprogramming adult peripheral blood mononuclear cells via transfection of OCT4, SOX2, KLF4, MYC, or LIN28 genes 21,22 . The resulting iPSC, similar to embryonic stem cells, retain the capacity to self‐renew, expand, and differentiate into all types of mature blood elements including RBCs 23–26 . From a basic research perspective, iPSC provides a powerful model to dissect mechanisms of cell differentiation.…”

“…21,22 The resulting iPSC, similar to embryonic stem cells, retain the capacity to selfrenew, expand, and differentiate into all types of mature blood elements including RBCs. [23][24][25][26] From a basic research perspective, iPSC provides a powerful model to dissect mechanisms of cell differentiation.…”