• Je něco špatně v tomto záznamu ?

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

P. Simara, L. Tesarova, D. Rehakova, S. Farkas, B. Salingova, K. Kutalkova, E. Vavreckova, P. Matula, P. Matula, L. Veverkova, I. Koutna,

. 2018 ; 27 (1) : 10-22. [pub] 20171211

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc19001108

Grantová podpora
NV16-31501A MZ0 CEP - Centrální evidence projektů

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 (γH2AX) 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 γH2AX 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.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc19001108
003      
CZ-PrNML
005      
20190122114025.0
007      
ta
008      
190107s2018 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1089/scd.2017.0132 $2 doi
035    __
$a (PubMed)29117787
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Simara, Pavel $u 1 Centre for Biomedical Image Analysis, Faculty of Informatics, Masaryk University , Brno, Czech Republic .
245    10
$a Reprogramming of Adult Peripheral Blood Cells into Human Induced Pluripotent Stem Cells as a Safe and Accessible Source of Endothelial Cells / $c P. Simara, L. Tesarova, D. Rehakova, S. Farkas, B. Salingova, K. Kutalkova, E. Vavreckova, P. Matula, P. Matula, L. Veverkova, I. Koutna,
520    9_
$a 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 (γH2AX) 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 γH2AX 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.
650    _2
$a biologické markery $x metabolismus $7 D015415
650    _2
$a buněčná diferenciace $x fyziologie $7 D002454
650    _2
$a kultivované buňky $7 D002478
650    _2
$a endoteliální buňky $x cytologie $x metabolismus $7 D042783
650    _2
$a fibroblasty $x cytologie $x metabolismus $7 D005347
650    _2
$a endoteliální buňky pupečníkové žíly (lidské) $x cytologie $x metabolismus $7 D061307
650    _2
$a lidé $7 D006801
650    _2
$a indukované pluripotentní kmenové buňky $x cytologie $x metabolismus $7 D057026
650    _2
$a leukocyty mononukleární $x cytologie $x metabolismus $7 D007963
650    _2
$a fyziologická neovaskularizace $x fyziologie $7 D018919
650    _2
$a regenerativní lékařství $x metody $7 D044968
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Tesarova, Lenka $u 1 Centre for Biomedical Image Analysis, Faculty of Informatics, Masaryk University , Brno, Czech Republic . 2 International Clinical Research Center, St. Anne's University Hospital Brno , Brno, Czech Republic .
700    1_
$a Rehakova, Daniela $u 1 Centre for Biomedical Image Analysis, Faculty of Informatics, Masaryk University , Brno, Czech Republic .
700    1_
$a Farkas, Simon $u 1 Centre for Biomedical Image Analysis, Faculty of Informatics, Masaryk University , Brno, Czech Republic .
700    1_
$a Salingova, Barbara $u 1 Centre for Biomedical Image Analysis, Faculty of Informatics, Masaryk University , Brno, Czech Republic .
700    1_
$a Kutalkova, Katerina $u 1 Centre for Biomedical Image Analysis, Faculty of Informatics, Masaryk University , Brno, Czech Republic .
700    1_
$a Vavreckova, Eva $u 1 Centre for Biomedical Image Analysis, Faculty of Informatics, Masaryk University , Brno, Czech Republic .
700    1_
$a Matula, Pavel $u 1 Centre for Biomedical Image Analysis, Faculty of Informatics, Masaryk University , Brno, Czech Republic .
700    1_
$a Matula, Petr $u 1 Centre for Biomedical Image Analysis, Faculty of Informatics, Masaryk University , Brno, Czech Republic .
700    1_
$a Veverkova, Lenka $u 3 I. Surgery Department, St. Anne's University Hospital Brno , Brno, Czech Republic .
700    1_
$a Koutna, Irena $u 1 Centre for Biomedical Image Analysis, Faculty of Informatics, Masaryk University , Brno, Czech Republic . 2 International Clinical Research Center, St. Anne's University Hospital Brno , Brno, Czech Republic .
773    0_
$w MED00162608 $t Stem cells and development $x 1557-8534 $g Roč. 27, č. 1 (2018), s. 10-22
856    41
$u https://pubmed.ncbi.nlm.nih.gov/29117787 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20190107 $b ABA008
991    __
$a 20190122114244 $b ABA008
999    __
$a ok $b bmc $g 1364005 $s 1039231
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2018 $b 27 $c 1 $d 10-22 $e 20171211 $i 1557-8534 $m Stem cells and development $n Stem Cells Dev $x MED00162608
GRA    __
$a NV16-31501A $p MZ0
LZP    __
$a Pubmed-20190107

Najít záznam

Citační ukazatele

Možnosti archivace