Significant improvement of direct reprogramming efficacy of fibroblasts into progenitor endothelial cells by ETV2 and hypoxia

Phuc Van Pham; Ngoc Bich Vu; Hoa Trong Nguyen; Oanh Thuy Huynh; Mai Thi-Hoang Truong; T Bogoslovsky; RG Shaffer; D Tasev; E Colombo; T Asahara; P Donndorf; YY Bai; SW Kim; J Kim; EB Peters; PV Phuc; CH Hu; CH Hu; A Schuh; C Kalka; A Kawamoto; W Suh; SK Cha; C Haller; DW Losordo; DW Losordo; DW Losordo; SH Li; Q She; JX Yu; A Flex; T Asahara; C Kalka; JM Isner; MC Yoder; MP White; L Wang; SJ Park; EA Kimbrel; R Lanza; OE Simonson; A Margariti; J Li; JK Han; R Morita; M Ginsberg; X Shi; MO Schupp; C Park; S Foja; H Shimada; Y Yoshida; K Iida; WK Nahm; L Zhou; V Falanga; F Liu; AN Behrens; I Elcheva; AG Lindgren; MB Veldman; S Lin; MP Craig; Z Zhang; J Jackson; A Minchenko; C Hitchon; DS Steinbrech; DS Steinbrech; EY Lee; J Rehman

doi:10.1186/s13287-016-0368-2

Significant improvement of direct reprogramming efficacy of fibroblasts into progenitor endothelial cells by ETV2 and hypoxia

Phuc Van Pham, Ngoc Bich Vu, Hoa Trong Nguyen, Oanh Thuy Huynh, Mai Thi-Hoang Truong, T Bogoslovsky, RG Shaffer, D Tasev, E Colombo, T Asahara, P Donndorf, YY Bai, SW Kim, J Kim, EB Peters, PV Phuc, CH Hu, CH Hu, A Schuh, C KalkaA Kawamoto, W Suh, SK Cha, C Haller, DW Losordo, DW Losordo, DW Losordo, SH Li, Q She, JX Yu, A Flex, T Asahara, C Kalka, JM Isner, MC Yoder, MP White, L Wang, SJ Park, EA Kimbrel, R Lanza, OE Simonson, A Margariti, J Li, JK Han, R Morita, M Ginsberg, X Shi, MO Schupp, C Park, S Foja, H Shimada, Y Yoshida, K Iida, WK Nahm, L Zhou, V Falanga, F Liu, AN Behrens, I Elcheva, AG Lindgren, MB Veldman, S Lin, MP Craig, Z Zhang, J Jackson, A Minchenko, C Hitchon, DS Steinbrech, DS Steinbrech, EY Lee, J Rehman

Research output: Chapter in Book/Report/Conference proceeding › Chapter

16 Citations (Scopus)

Abstract

Endothelial progenitor cell (EPC) transplantation is a promising therapy for ischemic diseases such as ischemic myocardial infarction and hindlimb ischemia. However, limitation of EPC sources remains a major obstacle. Direct reprogramming has become a powerful tool to produce EPCs from fibroblasts. Some recent efforts successfully directly reprogrammed human fibroblasts into functional EPCs; however, the procedure efficacy was low. This study therefore aimed to improve the efficacy of direct reprogramming of human fibroblasts to functional EPCs. Human fibroblasts isolated from foreskin were directly reprogrammed into EPCs by viral ETV2 transduction. Reprogramming efficacy was improved by culturing transduced fibroblasts in hypoxia conditions (5 % oxygen). Phenotype analyses confirmed that single-factor ETV2 transduction successfully reprogrammed dermal fibroblasts into functional EPCs. Hypoxia treatment during the reprogramming procedure increased the efficacy of reprogramming from 1.21 ± 0.61 % in normoxia conditions to 7.52 ± 2.31 % in hypoxia conditions. Induced EPCs in hypoxia conditions exhibited functional EPC phenotypes similar to those in normoxia conditions, such as expression of CD31 and VEGFR2, and expressed endothelial gene profiles similar to human umbilical vascular endothelial cells. These cells also formed capillary-like networks in vitro. Our study demonstrates a new simple method to increase the reprogramming efficacy of human fibroblasts to EPCs using ETV2 and hypoxia.

Original language	English
Title of host publication	Stem Cell Research & Therapy
Publisher	BioMed Central
Pages	104
Number of pages	1
ISBN (Print)	1328701603
DOIs	https://doi.org/10.1186/s13287-016-0368-2
Publication status	Published - 04 Dec 2016

Publication series

Name	Stem Cell Research & Therapy
Volume	7

Keywords

Cell Biology
Stem Cells

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1186/s13287-016-0368-2

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Van Pham, P., Vu, N. B., Nguyen, H. T., Huynh, O. T., Truong, M. T-H., Bogoslovsky, T., Shaffer, RG., Tasev, D., Colombo, E., Asahara, T., Donndorf, P., Bai, YY., Kim, SW., Kim, J., Peters, EB., Phuc, PV., Hu, CH., Hu, CH., Schuh, A., ... Rehman, J. (2016). Significant improvement of direct reprogramming efficacy of fibroblasts into progenitor endothelial cells by ETV2 and hypoxia. In Stem Cell Research & Therapy (pp. 104). (Stem Cell Research & Therapy; Vol. 7). BioMed Central. https://doi.org/10.1186/s13287-016-0368-2

@inbook{3365d32bc9194d6ba1329493681263fe,

title = "Significant improvement of direct reprogramming efficacy of fibroblasts into progenitor endothelial cells by ETV2 and hypoxia",

abstract = "Endothelial progenitor cell (EPC) transplantation is a promising therapy for ischemic diseases such as ischemic myocardial infarction and hindlimb ischemia. However, limitation of EPC sources remains a major obstacle. Direct reprogramming has become a powerful tool to produce EPCs from fibroblasts. Some recent efforts successfully directly reprogrammed human fibroblasts into functional EPCs; however, the procedure efficacy was low. This study therefore aimed to improve the efficacy of direct reprogramming of human fibroblasts to functional EPCs. Human fibroblasts isolated from foreskin were directly reprogrammed into EPCs by viral ETV2 transduction. Reprogramming efficacy was improved by culturing transduced fibroblasts in hypoxia conditions (5 % oxygen). Phenotype analyses confirmed that single-factor ETV2 transduction successfully reprogrammed dermal fibroblasts into functional EPCs. Hypoxia treatment during the reprogramming procedure increased the efficacy of reprogramming from 1.21 ± 0.61 % in normoxia conditions to 7.52 ± 2.31 % in hypoxia conditions. Induced EPCs in hypoxia conditions exhibited functional EPC phenotypes similar to those in normoxia conditions, such as expression of CD31 and VEGFR2, and expressed endothelial gene profiles similar to human umbilical vascular endothelial cells. These cells also formed capillary-like networks in vitro. Our study demonstrates a new simple method to increase the reprogramming efficacy of human fibroblasts to EPCs using ETV2 and hypoxia.",

keywords = "Cell Biology, Stem Cells",

author = "{Van Pham}, Phuc and Vu, {Ngoc Bich} and Nguyen, {Hoa Trong} and Huynh, {Oanh Thuy} and Truong, {Mai Thi-Hoang} and T Bogoslovsky and RG Shaffer and D Tasev and E Colombo and T Asahara and P Donndorf and YY Bai and SW Kim and J Kim and EB Peters and PV Phuc and CH Hu and CH Hu and A Schuh and C Kalka and A Kawamoto and W Suh and SK Cha and C Haller and DW Losordo and DW Losordo and DW Losordo and SH Li and Q She and JX Yu and A Flex and T Asahara and C Kalka and JM Isner and MC Yoder and MP White and L Wang and SJ Park and EA Kimbrel and R Lanza and OE Simonson and A Margariti and J Li and JK Han and R Morita and M Ginsberg and X Shi and MO Schupp and C Park and S Foja and H Shimada and Y Yoshida and K Iida and WK Nahm and L Zhou and V Falanga and F Liu and AN Behrens and I Elcheva and AG Lindgren and MB Veldman and S Lin and MP Craig and Z Zhang and J Jackson and A Minchenko and C Hitchon and DS Steinbrech and DS Steinbrech and EY Lee and J Rehman",

year = "2016",

month = dec,

day = "4",

doi = "10.1186/s13287-016-0368-2",

language = "English",

isbn = "1328701603",

series = "Stem Cell Research & Therapy",

publisher = "BioMed Central",

pages = "104",

booktitle = "Stem Cell Research & Therapy",

address = "United Kingdom",

}

Van Pham, P, Vu, NB, Nguyen, HT, Huynh, OT, Truong, MT-H, Bogoslovsky, T, Shaffer, RG, Tasev, D, Colombo, E, Asahara, T, Donndorf, P, Bai, YY, Kim, SW, Kim, J, Peters, EB, Phuc, PV, Hu, CH, Hu, CH, Schuh, A, Kalka, C, Kawamoto, A, Suh, W, Cha, SK, Haller, C, Losordo, DW, Losordo, DW, Losordo, DW, Li, SH, She, Q, Yu, JX, Flex, A, Asahara, T, Kalka, C, Isner, JM, Yoder, MC, White, MP, Wang, L, Park, SJ, Kimbrel, EA, Lanza, R, Simonson, OE, Margariti, A, Li, J, Han, JK, Morita, R, Ginsberg, M, Shi, X, Schupp, MO, Park, C, Foja, S, Shimada, H, Yoshida, Y, Iida, K, Nahm, WK, Zhou, L, Falanga, V, Liu, F, Behrens, AN, Elcheva, I, Lindgren, AG, Veldman, MB, Lin, S, Craig, MP, Zhang, Z, Jackson, J, Minchenko, A, Hitchon, C, Steinbrech, DS, Steinbrech, DS, Lee, EY & Rehman, J 2016, Significant improvement of direct reprogramming efficacy of fibroblasts into progenitor endothelial cells by ETV2 and hypoxia. in Stem Cell Research & Therapy. Stem Cell Research & Therapy, vol. 7, BioMed Central, pp. 104. https://doi.org/10.1186/s13287-016-0368-2

TY - CHAP

T1 - Significant improvement of direct reprogramming efficacy of fibroblasts into progenitor endothelial cells by ETV2 and hypoxia

AU - Van Pham, Phuc

AU - Vu, Ngoc Bich

AU - Nguyen, Hoa Trong

AU - Huynh, Oanh Thuy

AU - Truong, Mai Thi-Hoang

AU - Bogoslovsky, T

AU - Shaffer, RG

AU - Tasev, D

AU - Colombo, E

AU - Asahara, T

AU - Donndorf, P

AU - Bai, YY

AU - Kim, SW

AU - Kim, J

AU - Peters, EB

AU - Phuc, PV

AU - Hu, CH

AU - Schuh, A

AU - Kalka, C

AU - Kawamoto, A

AU - Suh, W

AU - Cha, SK

AU - Haller, C

AU - Losordo, DW

AU - Li, SH

AU - She, Q

AU - Yu, JX

AU - Flex, A

AU - Asahara, T

AU - Kalka, C

AU - Isner, JM

AU - Yoder, MC

AU - White, MP

AU - Wang, L

AU - Park, SJ

AU - Kimbrel, EA

AU - Lanza, R

AU - Simonson, OE

AU - Margariti, A

AU - Li, J

AU - Han, JK

AU - Morita, R

AU - Ginsberg, M

AU - Shi, X

AU - Schupp, MO

AU - Park, C

AU - Foja, S

AU - Shimada, H

AU - Yoshida, Y

AU - Iida, K

AU - Nahm, WK

AU - Zhou, L

AU - Falanga, V

AU - Liu, F

AU - Behrens, AN

AU - Elcheva, I

AU - Lindgren, AG

AU - Veldman, MB

AU - Lin, S

AU - Craig, MP

AU - Zhang, Z

AU - Jackson, J

AU - Minchenko, A

AU - Hitchon, C

AU - Steinbrech, DS

AU - Lee, EY

AU - Rehman, J

PY - 2016/12/4

Y1 - 2016/12/4

N2 - Endothelial progenitor cell (EPC) transplantation is a promising therapy for ischemic diseases such as ischemic myocardial infarction and hindlimb ischemia. However, limitation of EPC sources remains a major obstacle. Direct reprogramming has become a powerful tool to produce EPCs from fibroblasts. Some recent efforts successfully directly reprogrammed human fibroblasts into functional EPCs; however, the procedure efficacy was low. This study therefore aimed to improve the efficacy of direct reprogramming of human fibroblasts to functional EPCs. Human fibroblasts isolated from foreskin were directly reprogrammed into EPCs by viral ETV2 transduction. Reprogramming efficacy was improved by culturing transduced fibroblasts in hypoxia conditions (5 % oxygen). Phenotype analyses confirmed that single-factor ETV2 transduction successfully reprogrammed dermal fibroblasts into functional EPCs. Hypoxia treatment during the reprogramming procedure increased the efficacy of reprogramming from 1.21 ± 0.61 % in normoxia conditions to 7.52 ± 2.31 % in hypoxia conditions. Induced EPCs in hypoxia conditions exhibited functional EPC phenotypes similar to those in normoxia conditions, such as expression of CD31 and VEGFR2, and expressed endothelial gene profiles similar to human umbilical vascular endothelial cells. These cells also formed capillary-like networks in vitro. Our study demonstrates a new simple method to increase the reprogramming efficacy of human fibroblasts to EPCs using ETV2 and hypoxia.

AB - Endothelial progenitor cell (EPC) transplantation is a promising therapy for ischemic diseases such as ischemic myocardial infarction and hindlimb ischemia. However, limitation of EPC sources remains a major obstacle. Direct reprogramming has become a powerful tool to produce EPCs from fibroblasts. Some recent efforts successfully directly reprogrammed human fibroblasts into functional EPCs; however, the procedure efficacy was low. This study therefore aimed to improve the efficacy of direct reprogramming of human fibroblasts to functional EPCs. Human fibroblasts isolated from foreskin were directly reprogrammed into EPCs by viral ETV2 transduction. Reprogramming efficacy was improved by culturing transduced fibroblasts in hypoxia conditions (5 % oxygen). Phenotype analyses confirmed that single-factor ETV2 transduction successfully reprogrammed dermal fibroblasts into functional EPCs. Hypoxia treatment during the reprogramming procedure increased the efficacy of reprogramming from 1.21 ± 0.61 % in normoxia conditions to 7.52 ± 2.31 % in hypoxia conditions. Induced EPCs in hypoxia conditions exhibited functional EPC phenotypes similar to those in normoxia conditions, such as expression of CD31 and VEGFR2, and expressed endothelial gene profiles similar to human umbilical vascular endothelial cells. These cells also formed capillary-like networks in vitro. Our study demonstrates a new simple method to increase the reprogramming efficacy of human fibroblasts to EPCs using ETV2 and hypoxia.

KW - Cell Biology

KW - Stem Cells

U2 - 10.1186/s13287-016-0368-2

DO - 10.1186/s13287-016-0368-2

M3 - Chapter

C2 - 27488544

SN - 1328701603

T3 - Stem Cell Research & Therapy

SP - 104

BT - Stem Cell Research & Therapy

PB - BioMed Central

ER -

Significant improvement of direct reprogramming efficacy of fibroblasts into progenitor endothelial cells by ETV2 and hypoxia

Abstract

Publication series

Keywords

UN SDGs

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