Efficient Generation of β‐Globin‐Expressing Erythroid Cells Using Stromal Cell‐Derived Induced Pluripotent Stem Cells from Patients with Sickle Cell Disease. (26th October 2016)

• Record Type: Journal Article
• Authors: Uchida, Naoya; Haro‐Mora, Juan J.; Fujita, Atsushi; Lee, Duck‐Yeon; Winkler, Thomas; Hsieh, Matthew M.; Tisdale, John F.
• Is Part Of: Stem cells. Volume 35:Number 3(2017:Mar.)
• Page Start: 586
• Page End: 596
• Publication Date: 2016-10-26
• Subjects: Pluripotent stem cells -- Erythroid differentiation -- Primitive and definitive hematopoiesis -- Hemogenic endothelium; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.2517
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract: Human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells represent an ideal source for in vitro modeling of erythropoiesis and a potential alternative source for red blood cell transfusions. However, iPS cell‐derived erythroid cells predominantly produce ε‐ and γ‐globin without β‐globin production. We recently demonstrated that ES cell‐derived sacs (ES sacs), known to express hemangioblast markers, allow for efficient erythroid cell generation with β‐globin production. In this study, we generated several iPS cell lines derived from bone marrow stromal cells (MSCs) and peripheral blood erythroid progenitors (EPs) from sickle cell disease patients, and evaluated hematopoietic stem/progenitor cell (HSPC) generation after iPS sac induction as well as subsequent erythroid differentiation. MSC‐derived iPS sacs yielded greater amounts of immature hematopoietic progenitors (VEGFR2 + GPA−), definitive HSPCs (CD34 + CD45+), and megakaryoerythroid progenitors (GPA + CD41a+), as compared to EP‐derived iPS sacs. Erythroid differentiation from MSC‐derived iPS sacs resulted in greater amounts of erythroid cells (GPA+) and higher β‐globin (and βS‐globin) expression, comparable to ES sac‐derived cells. These data demonstrate that human MSC‐derived iPS sacs allow for more efficient erythroid cell generation with higher β‐globin production, likely due to heightened emergence of immature progenitors. Our findings should be important for iPS cell‐derived erythroid cell generation. Stem Cells 2017;35:586–596 Abstract : We generated βS‐globin expressing definitive erythroid cells thorough hemangioblast‐like iPS sacs derived from both stromal cells and erythroid progenitors in sickle cell disease patients. The stromal cell‐derived iPS sacs allow for more efficient erythroid cell generation with higher βS‐globin production, and this occurs through a heightened emergence of immature hematopoietic progenitors in stromal cell‐derived iPS sacs. The reliable production of βS‐globin from iPS cells is important to investigate pathogenic erythropoiesis in vitro and develop therapeutic strategies with genetic modification for sickle cell disease.