J 2018

Reprogramming of Adult Peripheral Blood Cells into Human Induced Pluripotent Stem Cells as a Safe and Accessible Source of Endothelial Cells.

ŠIMARA, Pavel, Lenka TESAŘOVÁ, Daniela ŘEHÁKOVÁ, Šimon FARKAŠ, Barbara ŠALINGOVÁ et. al.

Basic information

Original name

Reprogramming of Adult Peripheral Blood Cells into Human Induced Pluripotent Stem Cells as a Safe and Accessible Source of Endothelial Cells.

Authors

ŠIMARA, Pavel (203 Czech Republic, belonging to the institution), Lenka TESAŘOVÁ (203 Czech Republic, belonging to the institution), Daniela ŘEHÁKOVÁ (203 Czech Republic, belonging to the institution), Šimon FARKAŠ (703 Slovakia, belonging to the institution), Barbara ŠALINGOVÁ (703 Slovakia, belonging to the institution), Kateřina KUTÁLKOVÁ (203 Czech Republic, belonging to the institution), Eva VAVREČKOVÁ (203 Czech Republic, belonging to the institution), Pavel MATULA (203 Czech Republic, belonging to the institution), Petr MATULA (203 Czech Republic, belonging to the institution), Lenka VEVERKOVÁ (203 Czech Republic) and Irena KRONTORÁD KOUTNÁ (203 Czech Republic, guarantor, belonging to the institution)

Edition

Stem Cells and Development, Mary Ann Liebert, Inc. publishers, 2018, 1547-3287

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10601 Cell biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 3.147

RIV identification code

RIV/00216224:14330/18:00100772

Organization unit

Faculty of Informatics

UT WoS

000417686200001

Keywords in English

induced pluripotent stem cells; endothelial differentiation; peripheral blood mononuclear cells

Tags

Tags

International impact, Reviewed
Změněno: 29/4/2019 16:10, RNDr. Pavel Šmerk, Ph.D.

Abstract

V originále

New approaches in regenerative medicine and vasculogenesis have generated a demand for sufficient numbers of human endothelial cells (ECs). ECs and their progenitors reside on the interior surface of blood and lymphatic vessels or circulate in peripheral blood; however, their numbers are limited, and they are difficult to expand after isolation. Recent advances in human induced pluripotent stem cell (hiPSC) research have opened possible avenues to generate unlimited numbers of ECs from easily accessible cell sources, such as the peripheral blood. In this study, we reprogrammed peripheral blood mononuclear cells, human umbilical vein endothelial cells (HUVECs), and human saphenous vein endothelial cells (HSVECs) into hiPSCs and differentiated them into ECs. The phenotype profiles, functionality, and genome stability of all hiPSC-derived ECs were assessed and compared with HUVECs and HSVECs. hiPSC-derived ECs resembled their natural EC counterparts, as shown by the expression of the endothelial surface markers CD31 and CD144 and the results of the functional analysis. Higher expression of endothelial progenitor markers CD34 and kinase insert domain receptor (KDR) was measured in hiPSC-derived ECs. An analysis of phosphorylated histone H2AX (gamma-H2AX) foci revealed that an increased number of DNA double-strand breaks upon reprogramming into pluripotent cells. However, differentiation into ECs restored a normal number of gamma-H2AX foci. Our hiPSCs retained a normal karyotype, with the exception of the HSVEC-derived hiPSC line, which displayed mosaicism due to a gain of chromosome 1. Peripheral blood from adult donors is a suitable source for the unlimited production of patient-specific ECs through the hiPSC interstage. hiPSC-derived ECs are fully functional and comparable to natural ECs. The protocol is eligible for clinical applications in regenerative medicine, if the genomic stability of the pluripotent cell stage is closely monitored.

Links

GBP302/12/G157, research and development project
Name: Dynamika a organizace chromosomů během buněčného cyklu a při diferenciaci v normě a patologii
Investor: Czech Science Foundation
NV16-31501A, research and development project
Name: Tkáňové inženýrství epitelů: Buňky a protokoly pro regenerativní medicínu