1549-4918/asset/cover.gif?v=1&s=51ac62b4272cd760b70f0cb1539035cc40743da6 "STEM CELLS")
Telephone: 508-791-0305 extension 684, Fax: 508-756-4468
1549-4918/asset/olbannerleft.jpg?v=1&s=699114e871887e6b838f6a1c657fe256cfe127a6)
1549-4918/asset/olbannerright.gif?v=1&s=603f8f2ab5cd9d4f783c231915608956af51aeea)
Embryonic Stem Cells/Induced Pluripotent Stem Cells
You have free access to this content
Hemangioblastic Derivatives from Human Induced Pluripotent Stem Cells Exhibit Limited Expansion and Early Senescence†‡§
Article first published online: 12 FEB 2010
DOI: 10.1002/stem.321
Copyright © 2010 AlphaMed Press
Additional Information
How to Cite
Feng, Q., Lu, S.-J., Klimanskaya, I., Gomes, I., Kim, D., Chung, Y., Honig, G. R., Kim, K.-S. and Lanza, R. (2010), Hemangioblastic Derivatives from Human Induced Pluripotent Stem Cells Exhibit Limited Expansion and Early Senescence. STEM CELLS, 28: 704–712. doi: 10.1002/stem.321
- †
Author contributions: Q.F.: Conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing; S-J.L.: Conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing, and final approval of manuscript; I.K., I.G., D.K., Y.C.: Collection and assembly of data; G.H.: Data analysis and interpretation; K-S.K.: Collection and assembly of data, data analysis and interpretation; R.L.: Conception and design, data analysis and interpretation, manuscript writing, and final approval of manuscript.
- ‡
First published online in STEM CELLS EXPRESS February 4, 2010.
- §
Disclosure of potential conflicts of interest is found at the end of this article.
- ¶
Telephone: 508-791-0305 extension 684, Fax: 508-756-4468
- ‖
Telephone: 508-756-1212 extension 655, Fax: 508-756-4468
Publication History
- Issue published online: 14 APR 2010
- Article first published online: 12 FEB 2010
- Manuscript Accepted: 4 FEB 2010
- Manuscript Received: 15 DEC 2009
Keywords:
- Differentiation;
- Pluripotent stem cells;
- Embryonic stem cells;
- Endothelial differentiation;
- Hemangioblast;
- Hematopoietic cells;
- Proliferation;
- Reprogramming
Abstract
Human induced pluripotent stem cells (hiPSC) have been shown to differentiate into a variety of replacement cell types. Detailed evaluation and comparison with their human embryonic stem cell (hESC) counterparts is critical for assessment of their therapeutic potential. Using established methods, we demonstrate here that hiPSCs are capable of generating hemangioblasts/blast cells (BCs), endothelial cells, and hematopoietic cells with phenotypic and morphologic characteristics similar to those derived from hESCs, but with a dramatic decreased efficiency. Furthermore, in distinct contrast with the hESC derivatives, functional differences were observed in BCs derived from hiPSCs, including significantly increased apoptosis, severely limited growth and expansion capability, and a substantially decreased hematopoietic colony-forming capability. After further differentiation into erythroid cells, >1,000-fold difference in expansion capability was observed in hiPSC-BCs versus hESC-BCs. Although endothelial cells derived from hiPSCs were capable of taking up acetylated low-density lipoprotein and forming capillary-vascular-like structures on Matrigel, these cells also demonstrated early cellular senescence (most of the endothelial cells senesced after one passage). Similarly, retinal pigmented epithelium cells derived from hiPSCs began senescing in the first passage. Before clinical application, it will be necessary to determine the cause and extent of such abnormalities and whether they also occur in hiPSCs generated using different reprogramming methods. STEM CELLS 2010;28:704–712