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Published in: Journal of Translational Medicine 1/2013

Open Access 01-12-2013 | Research

Identical effects of VEGF and serum-deprivation on phenotype and function of adipose-derived stromal cells from healthy donors and patients with ischemic heart disease

Authors: Bjarke Follin, Josefine Tratwal, Mandana Haack-Sørensen, Jens Jørgen Elberg, Jens Kastrup, Annette Ekblond

Published in: Journal of Translational Medicine | Issue 1/2013

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Abstract

Background

Adipose-derived stromal cells (ASCs) stimulated with vascular endothelial growth factor (VEGF) and serum-deprived, are applied in the first in-man double-blind placebo-controlled MyStromalCell Trial, as a novel therapeutic option for treatment of ischemic heart disease (IHD). This in vitro study explored the effect of VEGF and serum deprivation on endothelial differentiation capacity of ASCs from healthy donors and IHD patients.

Methods

ASCs stimulated with rhVEGFA165 in serum-deprived medium for one to three weeks were compared with ASCs in serum-deprived (2% fetal bovine serum) or complete medium (10% fetal bovine serum). Expression of VEGF receptors, endothelial and stem cell markers was measured using qPCR, flow cytometry and immunocytochemistry. In vitro tube formation and proliferation was also measured.

Results

ASCs from VEGF-stimulated and serum-deprived medium significantly increased transcription of transcription factor FOXF1, endothelial marker vWF and receptor VEGFR1 compared with ASCs from complete medium. ASCs maintained stem cell characteristics in all conditions. Tube formation of ASCs occurred in VEGF-stimulated and serum-deprived medium. The only difference between healthy and patient ASCs was a variation in proliferation rate.

Conclusions

ASCs from IHD patients and healthy donors proved equally inclined to differentiate in endothelial direction by serum-deprivation, however with no visible additive effect of VEGF stimulation. The treatment did not result in complete endothelial differentiation, but priming towards endothelial lineage.
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Literature
1.
go back to reference The Top 10 Causes of Death. Curr Probl Cardiol. 2010, 35: 72-115. 10.1016/j.cpcardiol.2009.10.002. doi:10.1016/j.cpcardiol.2009.10.002.NIH The Top 10 Causes of Death. Curr Probl Cardiol. 2010, 35: 72-115. 10.1016/j.cpcardiol.2009.10.002. doi:10.1016/j.cpcardiol.2009.10.002.NIH
2.
go back to reference Swinburn BA, Sacks G, Hall KD, McPherson K, Finegood DT, Moodie ML, Gortmaker SL: The global obesity pandemic: shaped by global drivers and local environments. Lancet. 2011, 378: 804-814. 10.1016/S0140-6736(11)60813-1.CrossRefPubMed Swinburn BA, Sacks G, Hall KD, McPherson K, Finegood DT, Moodie ML, Gortmaker SL: The global obesity pandemic: shaped by global drivers and local environments. Lancet. 2011, 378: 804-814. 10.1016/S0140-6736(11)60813-1.CrossRefPubMed
3.
go back to reference LaPar DJ, Kron IL, Yang Z: Stem cell therapy for ischemic heart disease: where are we?. Curr Opin Organ Transplant. 2009, 14: 79-84. 10.1097/MOT.0b013e328320d2e2.CrossRefPubMed LaPar DJ, Kron IL, Yang Z: Stem cell therapy for ischemic heart disease: where are we?. Curr Opin Organ Transplant. 2009, 14: 79-84. 10.1097/MOT.0b013e328320d2e2.CrossRefPubMed
4.
go back to reference Kastrup J: Stem cells therapy for cardiovascular repair in ischemic heart disease: How to predict and secure optimal outcome?. EPMA J. 2011, 2 (1): 107-117. 10.1007/s13167-011-0062-5.PubMedCentralCrossRefPubMed Kastrup J: Stem cells therapy for cardiovascular repair in ischemic heart disease: How to predict and secure optimal outcome?. EPMA J. 2011, 2 (1): 107-117. 10.1007/s13167-011-0062-5.PubMedCentralCrossRefPubMed
5.
go back to reference Sanchez PL, San Roman JA, Villa A, Fernandez ME, Fernandez-Aviles F: Contemplating the bright future of stem cell therapy for cardiovascular disease. Nat Clin Pract Cardiovasc Med. 2006, 3 (Suppl 1): S138-S151.CrossRefPubMed Sanchez PL, San Roman JA, Villa A, Fernandez ME, Fernandez-Aviles F: Contemplating the bright future of stem cell therapy for cardiovascular disease. Nat Clin Pract Cardiovasc Med. 2006, 3 (Suppl 1): S138-S151.CrossRefPubMed
6.
go back to reference Singer NG, Caplan AI: Mesenchymal stem cells: mechanisms of inflammation. Annu Rev Pathol. 2011, 6: 457-478. 10.1146/annurev-pathol-011110-130230.CrossRefPubMed Singer NG, Caplan AI: Mesenchymal stem cells: mechanisms of inflammation. Annu Rev Pathol. 2011, 6: 457-478. 10.1146/annurev-pathol-011110-130230.CrossRefPubMed
7.
go back to reference Mathiasen AB, Haack-Sorensen M, Kastrup J: Mesenchymal stromal cells for cardiovascular repair: current status and future challenges. Future Cardiol. 2009, 5: 605-617. 10.2217/fca.09.42.CrossRefPubMed Mathiasen AB, Haack-Sorensen M, Kastrup J: Mesenchymal stromal cells for cardiovascular repair: current status and future challenges. Future Cardiol. 2009, 5: 605-617. 10.2217/fca.09.42.CrossRefPubMed
8.
go back to reference Li J, 1, WH-SW, 2, SC, JC-SC, KM-CC, 4, Lee2 T-L: Factors Affecting Mesenchymal Stromal Cells Yield from Bone Marrow Aspiration Chin. J Cancer Res. 2011, 23: 43-48. Li J, 1, WH-SW, 2, SC, JC-SC, KM-CC, 4, Lee2 T-L: Factors Affecting Mesenchymal Stromal Cells Yield from Bone Marrow Aspiration Chin. J Cancer Res. 2011, 23: 43-48.
9.
go back to reference Zhu Y, Liu T, Song K, Fan X, Ma X, Cui Z: Adipose-derived stem cell: a better stem cell than BMSC. Cell Biochem Funct. 2008, 26: 664-675. 10.1002/cbf.1488.CrossRefPubMed Zhu Y, Liu T, Song K, Fan X, Ma X, Cui Z: Adipose-derived stem cell: a better stem cell than BMSC. Cell Biochem Funct. 2008, 26: 664-675. 10.1002/cbf.1488.CrossRefPubMed
10.
go back to reference Cowan CM, Shi YY, Aalami OO, Chou YF, Mari C, Thomas R, Quarto N, Contag CH, Wu B, Longaker MT: Adipose-derived adult stromal cells heal critical-size mouse calvarial defects. Nat Biotechnol. 2004, 22: 560-567. 10.1038/nbt958.CrossRefPubMed Cowan CM, Shi YY, Aalami OO, Chou YF, Mari C, Thomas R, Quarto N, Contag CH, Wu B, Longaker MT: Adipose-derived adult stromal cells heal critical-size mouse calvarial defects. Nat Biotechnol. 2004, 22: 560-567. 10.1038/nbt958.CrossRefPubMed
11.
go back to reference Noel D, Caton D, Roche S, Bony C, Lehmann S, Casteilla L, Jorgensen C, Cousin B: Cell specific differences between human adipose-derived and mesenchymal-stromal cells despite similar differentiation potentials. Exp Cell Res. 2008, 314: 1575-1584. 10.1016/j.yexcr.2007.12.022.CrossRefPubMed Noel D, Caton D, Roche S, Bony C, Lehmann S, Casteilla L, Jorgensen C, Cousin B: Cell specific differences between human adipose-derived and mesenchymal-stromal cells despite similar differentiation potentials. Exp Cell Res. 2008, 314: 1575-1584. 10.1016/j.yexcr.2007.12.022.CrossRefPubMed
12.
go back to reference Valina C, Pinkernell K, Song YH, Bai X, Sadat S, Campeau RJ, Le Jemtel TH, Alt E: Intracoronary administration of autologous adipose tissue-derived stem cells improves left ventricular function, perfusion, and remodelling after acute myocardial infarction. Eur Heart J. 2007, 28: 2667-2677. 10.1093/eurheartj/ehm426.CrossRefPubMed Valina C, Pinkernell K, Song YH, Bai X, Sadat S, Campeau RJ, Le Jemtel TH, Alt E: Intracoronary administration of autologous adipose tissue-derived stem cells improves left ventricular function, perfusion, and remodelling after acute myocardial infarction. Eur Heart J. 2007, 28: 2667-2677. 10.1093/eurheartj/ehm426.CrossRefPubMed
13.
go back to reference Yoon CH, Koyanagi M, Iekushi K, Seeger F, Urbich C, Zeiher AM, Dimmeler S: Mechanism of improved cardiac function after bone marrow mononuclear cell therapy: role of cardiovascular lineage commitment. Circulation. 2010, 121: 2001-2011. 10.1161/CIRCULATIONAHA.109.909291.CrossRefPubMed Yoon CH, Koyanagi M, Iekushi K, Seeger F, Urbich C, Zeiher AM, Dimmeler S: Mechanism of improved cardiac function after bone marrow mononuclear cell therapy: role of cardiovascular lineage commitment. Circulation. 2010, 121: 2001-2011. 10.1161/CIRCULATIONAHA.109.909291.CrossRefPubMed
14.
go back to reference Oswald J, Boxberger S, Jorgensen B, Feldmann S, Ehninger G, Bornhauser M, Werner C: Mesenchymal stem cells can be differentiated into endothelial cells in vitro. Stem Cells. 2004, 22: 377-384. 10.1634/stemcells.22-3-377.CrossRefPubMed Oswald J, Boxberger S, Jorgensen B, Feldmann S, Ehninger G, Bornhauser M, Werner C: Mesenchymal stem cells can be differentiated into endothelial cells in vitro. Stem Cells. 2004, 22: 377-384. 10.1634/stemcells.22-3-377.CrossRefPubMed
15.
go back to reference Haack-Sorensen M, Friis T, Bindslev L, Mortensen S, Johnsen HE, Kastrup J: Comparison of different culture conditions for human mesenchymal stromal cells for clinical stem cell therapy. Scand J Clin Lab Invest. 2008, 68: 192-203. 10.1080/00365510701601681.CrossRefPubMed Haack-Sorensen M, Friis T, Bindslev L, Mortensen S, Johnsen HE, Kastrup J: Comparison of different culture conditions for human mesenchymal stromal cells for clinical stem cell therapy. Scand J Clin Lab Invest. 2008, 68: 192-203. 10.1080/00365510701601681.CrossRefPubMed
16.
go back to reference Silva GV, Litovsky S, Assad JA, Sousa AL, Martin BJ, Vela D, Coulter SC, Lin J, Ober J, Vaughn WK: Mesenchymal stem cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a canine chronic ischemia model. Circulation. 2005, 111: 150-156. 10.1161/01.CIR.0000151812.86142.45.CrossRefPubMed Silva GV, Litovsky S, Assad JA, Sousa AL, Martin BJ, Vela D, Coulter SC, Lin J, Ober J, Vaughn WK: Mesenchymal stem cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a canine chronic ischemia model. Circulation. 2005, 111: 150-156. 10.1161/01.CIR.0000151812.86142.45.CrossRefPubMed
17.
go back to reference Reyes M, Dudek A, Jahagirdar B, Koodie L, Marker PH, Verfaillie CM: Origin of endothelial progenitors in human postnatal bone marrow. J Clin Invest. 2002, 109: 337-346.PubMedCentralCrossRefPubMed Reyes M, Dudek A, Jahagirdar B, Koodie L, Marker PH, Verfaillie CM: Origin of endothelial progenitors in human postnatal bone marrow. J Clin Invest. 2002, 109: 337-346.PubMedCentralCrossRefPubMed
18.
go back to reference Mathiasen AB, Jorgensen E, Qayyum AA, Haack-Sorensen M, Ekblond A, Kastrup J: Rationale and design of the first randomized, double-blind, placebo-controlled trial of intramyocardial injection of autologous bone-marrow derived Mesenchymal Stromal Cells in chronic ischemic Heart Failure (MSC-HF Trial). Am Heart J. 2012, 164: 285-291. 10.1016/j.ahj.2012.05.026.CrossRefPubMed Mathiasen AB, Jorgensen E, Qayyum AA, Haack-Sorensen M, Ekblond A, Kastrup J: Rationale and design of the first randomized, double-blind, placebo-controlled trial of intramyocardial injection of autologous bone-marrow derived Mesenchymal Stromal Cells in chronic ischemic Heart Failure (MSC-HF Trial). Am Heart J. 2012, 164: 285-291. 10.1016/j.ahj.2012.05.026.CrossRefPubMed
19.
go back to reference Haack-Sorensen M, Friis T, Mathiasen AB, Jorgensen E, Hansen L, Dickmeiss E, Ekblond A, Kastrup J: Direct intramyocardial mesenchymal stromal cell injections in patients with severe refractory angina - one year follow-up. Cell Transplant. 2013, 22 (3): 521-528. 10.3727/096368912X636830.CrossRefPubMed Haack-Sorensen M, Friis T, Mathiasen AB, Jorgensen E, Hansen L, Dickmeiss E, Ekblond A, Kastrup J: Direct intramyocardial mesenchymal stromal cell injections in patients with severe refractory angina - one year follow-up. Cell Transplant. 2013, 22 (3): 521-528. 10.3727/096368912X636830.CrossRefPubMed
20.
go back to reference Friis T, Haack-Sorensen M, Mathiasen AB, Ripa RS, Kristoffersen US, Jorgensen E, Hansen L, Bindslev L, Kjaer A, Hesse B: Mesenchymal stromal cell derived endothelial progenitor treatment in patients with refractory angina. Scand Cardiovasc J. 2011, 45: 161-168. 10.3109/14017431.2011.569571.CrossRefPubMed Friis T, Haack-Sorensen M, Mathiasen AB, Ripa RS, Kristoffersen US, Jorgensen E, Hansen L, Bindslev L, Kjaer A, Hesse B: Mesenchymal stromal cell derived endothelial progenitor treatment in patients with refractory angina. Scand Cardiovasc J. 2011, 45: 161-168. 10.3109/14017431.2011.569571.CrossRefPubMed
21.
go back to reference Cao Y, Sun Z, Liao L, Meng Y, Han Q, Zhao RC: Human adipose tissue-derived stem cells differentiate into endothelial cells in vitro and improve postnatal neovascularization in vivo. Biochem Biophys Res Commun. 2005, 332: 370-379. 10.1016/j.bbrc.2005.04.135.CrossRefPubMed Cao Y, Sun Z, Liao L, Meng Y, Han Q, Zhao RC: Human adipose tissue-derived stem cells differentiate into endothelial cells in vitro and improve postnatal neovascularization in vivo. Biochem Biophys Res Commun. 2005, 332: 370-379. 10.1016/j.bbrc.2005.04.135.CrossRefPubMed
22.
go back to reference Moon MH, Kim SY, Kim YJ, Kim SJ, Lee JB, Bae YC, Sung SM, Jung JS: Human adipose tissue-derived mesenchymal stem cells improve postnatal neovascularization in a mouse model of hindlimb ischemia. Cell Physiol Biochem. 2006, 17: 279-290. 10.1159/000094140.CrossRefPubMed Moon MH, Kim SY, Kim YJ, Kim SJ, Lee JB, Bae YC, Sung SM, Jung JS: Human adipose tissue-derived mesenchymal stem cells improve postnatal neovascularization in a mouse model of hindlimb ischemia. Cell Physiol Biochem. 2006, 17: 279-290. 10.1159/000094140.CrossRefPubMed
23.
go back to reference Qayyum AA, Haack-Sorensen M, Mathiasen AB, Jorgensen E, Ekblond A, Kastrup J: Adipose-derived mesenchymal stromal cells for chronic myocardial ischemia (MyStromalCell Trial): study design. Regen Med. 2012, 7: 421-428. 10.2217/rme.12.17.CrossRefPubMed Qayyum AA, Haack-Sorensen M, Mathiasen AB, Jorgensen E, Ekblond A, Kastrup J: Adipose-derived mesenchymal stromal cells for chronic myocardial ischemia (MyStromalCell Trial): study design. Regen Med. 2012, 7: 421-428. 10.2217/rme.12.17.CrossRefPubMed
24.
go back to reference Abdel-Latif A, Bolli R, Tleyjeh IM, Montori VM, Perin EC, Hornung CA, Zuba-Surma EK, Al-Mallah M, Dawn B: Adult bone marrow-derived cells for cardiac repair: a systematic review and meta-analysis. Arch Intern Med. 2007, 167: 989-997. 10.1001/archinte.167.10.989.CrossRefPubMed Abdel-Latif A, Bolli R, Tleyjeh IM, Montori VM, Perin EC, Hornung CA, Zuba-Surma EK, Al-Mallah M, Dawn B: Adult bone marrow-derived cells for cardiac repair: a systematic review and meta-analysis. Arch Intern Med. 2007, 167: 989-997. 10.1001/archinte.167.10.989.CrossRefPubMed
25.
26.
go back to reference Alt EU, Senst C, Murthy SN, Slakey DP, Dupin CL, Chaffin AE, Kadowitz PJ, Izadpanah R: Aging alters tissue resident mesenchymal stem cell properties. Stem Cell Res. 2012, 8: 215-225. 10.1016/j.scr.2011.11.002.CrossRefPubMed Alt EU, Senst C, Murthy SN, Slakey DP, Dupin CL, Chaffin AE, Kadowitz PJ, Izadpanah R: Aging alters tissue resident mesenchymal stem cell properties. Stem Cell Res. 2012, 8: 215-225. 10.1016/j.scr.2011.11.002.CrossRefPubMed
27.
go back to reference Efimenko A, Starostina E, Kalinina N, Stolzing A: Angiogenic properties of aged adipose derived mesenchymal stem cells after hypoxic conditioning. J Transl Med. 2011, 9: 10-10.1186/1479-5876-9-10.PubMedCentralCrossRefPubMed Efimenko A, Starostina E, Kalinina N, Stolzing A: Angiogenic properties of aged adipose derived mesenchymal stem cells after hypoxic conditioning. J Transl Med. 2011, 9: 10-10.1186/1479-5876-9-10.PubMedCentralCrossRefPubMed
28.
go back to reference Chen HT, Lee MJ, Chen CH, Chuang SC, Chang LF, Ho ML, Hung SH, Fu YC, Wang YH, Wang HI: Proliferation and differentiation potential of human adipose-derived mesenchymal stem cells isolated from elderly patients with osteoporotic fractures. J Cell Mol Med. 2012, 16: 582-593. 10.1111/j.1582-4934.2011.01335.x.PubMedCentralCrossRefPubMed Chen HT, Lee MJ, Chen CH, Chuang SC, Chang LF, Ho ML, Hung SH, Fu YC, Wang YH, Wang HI: Proliferation and differentiation potential of human adipose-derived mesenchymal stem cells isolated from elderly patients with osteoporotic fractures. J Cell Mol Med. 2012, 16: 582-593. 10.1111/j.1582-4934.2011.01335.x.PubMedCentralCrossRefPubMed
29.
go back to reference Friis T, Haack-Soorensen M, Hansen SK, Hansen L, Bindslev L, Kastrup J: Comparison of mesenchymal stromal cells from young healthy donors and patients with severe chronic coronary artery disease. Scand J Clin Lab Invest. 2011, 71: 193-202. 10.3109/00365513.2010.550310.CrossRefPubMed Friis T, Haack-Soorensen M, Hansen SK, Hansen L, Bindslev L, Kastrup J: Comparison of mesenchymal stromal cells from young healthy donors and patients with severe chronic coronary artery disease. Scand J Clin Lab Invest. 2011, 71: 193-202. 10.3109/00365513.2010.550310.CrossRefPubMed
30.
go back to reference Zhang P, Moudgill N, Hager E, Tarola N, Dimatteo C, McIlhenny S, Tulenko T, DiMuzio PJ: Endothelial differentiation of adipose-derived stem cells from elderly patients with cardiovascular disease. Stem Cells Dev. 2011, 20: 977-988. 10.1089/scd.2010.0152.PubMedCentralCrossRefPubMed Zhang P, Moudgill N, Hager E, Tarola N, Dimatteo C, McIlhenny S, Tulenko T, DiMuzio PJ: Endothelial differentiation of adipose-derived stem cells from elderly patients with cardiovascular disease. Stem Cells Dev. 2011, 20: 977-988. 10.1089/scd.2010.0152.PubMedCentralCrossRefPubMed
31.
go back to reference Haack-Sorensen M, Kastrup J: Cryopreservation and revival of mesenchymal stromal cells. Methods Mol Biol. 2011, 698: 161-174. 10.1007/978-1-60761-999-4_13.CrossRefPubMed Haack-Sorensen M, Kastrup J: Cryopreservation and revival of mesenchymal stromal cells. Methods Mol Biol. 2011, 698: 161-174. 10.1007/978-1-60761-999-4_13.CrossRefPubMed
32.
go back to reference Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 2001, 25: 402-408. 10.1006/meth.2001.1262.CrossRefPubMed Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 2001, 25: 402-408. 10.1006/meth.2001.1262.CrossRefPubMed
33.
go back to reference Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop D, Horwitz E: Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006, 8: 315-317. 10.1080/14653240600855905.CrossRefPubMed Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop D, Horwitz E: Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006, 8: 315-317. 10.1080/14653240600855905.CrossRefPubMed
34.
go back to reference Astorga J, Carlsson P: Hedgehog induction of murine vasculogenesis is mediated by Foxf1 and Bmp4. Development. 2007, 134: 3753-3761. 10.1242/dev.004432.CrossRefPubMed Astorga J, Carlsson P: Hedgehog induction of murine vasculogenesis is mediated by Foxf1 and Bmp4. Development. 2007, 134: 3753-3761. 10.1242/dev.004432.CrossRefPubMed
35.
go back to reference Lo PK, Lee JS, Liang X, Han L, Mori T, Fackler MJ, Sadik H, Argani P, Pandita TK, Sukumar S: Epigenetic inactivation of the potential tumor suppressor gene FOXF1 in breast cancer. Cancer Res. 2010, 70: 6047-6058. 10.1158/0008-5472.CAN-10-1576.PubMedCentralCrossRefPubMed Lo PK, Lee JS, Liang X, Han L, Mori T, Fackler MJ, Sadik H, Argani P, Pandita TK, Sukumar S: Epigenetic inactivation of the potential tumor suppressor gene FOXF1 in breast cancer. Cancer Res. 2010, 70: 6047-6058. 10.1158/0008-5472.CAN-10-1576.PubMedCentralCrossRefPubMed
36.
go back to reference Lo PK, Lee JS, Sukumar S: The p53-p21WAF1 checkpoint pathway plays a protective role in preventing DNA rereplication induced by abrogation of FOXF1 function. Cell Signal. 2012, 24: 316-324. 10.1016/j.cellsig.2011.09.017.PubMedCentralCrossRefPubMed Lo PK, Lee JS, Sukumar S: The p53-p21WAF1 checkpoint pathway plays a protective role in preventing DNA rereplication induced by abrogation of FOXF1 function. Cell Signal. 2012, 24: 316-324. 10.1016/j.cellsig.2011.09.017.PubMedCentralCrossRefPubMed
37.
go back to reference Nilsson J, Helou K, Kovacs A, Bendahl PO, Bjursell G, Ferno M, Carlsson P, Kannius-Janson M: Nuclear Janus-activated kinase 2/nuclear factor 1-C2 suppresses tumorigenesis and epithelial-to-mesenchymal transition by repressing Forkhead box F1. Cancer Res. 2010, 70: 2020-2029. 10.1158/0008-5472.CAN-09-1677.CrossRefPubMed Nilsson J, Helou K, Kovacs A, Bendahl PO, Bjursell G, Ferno M, Carlsson P, Kannius-Janson M: Nuclear Janus-activated kinase 2/nuclear factor 1-C2 suppresses tumorigenesis and epithelial-to-mesenchymal transition by repressing Forkhead box F1. Cancer Res. 2010, 70: 2020-2029. 10.1158/0008-5472.CAN-09-1677.CrossRefPubMed
38.
go back to reference Ball SG, Shuttleworth CA, Kielty CM: Vascular endothelial growth factor can signal through platelet-derived growth factor receptors. J Cell Biol. 2007, 177: 489-500. 10.1083/jcb.200608093.PubMedCentralCrossRefPubMed Ball SG, Shuttleworth CA, Kielty CM: Vascular endothelial growth factor can signal through platelet-derived growth factor receptors. J Cell Biol. 2007, 177: 489-500. 10.1083/jcb.200608093.PubMedCentralCrossRefPubMed
39.
go back to reference Waltenberger J, Claesson-Welsh L, Siegbahn A, Shibuya M, Heldin CH: Different signal transduction properties of KDR and Flt1, two receptors for vascular endothelial growth factor. J Biol Chem. 1994, 269: 26988-26995.PubMed Waltenberger J, Claesson-Welsh L, Siegbahn A, Shibuya M, Heldin CH: Different signal transduction properties of KDR and Flt1, two receptors for vascular endothelial growth factor. J Biol Chem. 1994, 269: 26988-26995.PubMed
40.
go back to reference Kearney JB, Kappas NC, Ellerstrom C, DiPaola FW, Bautch VL: The VEGF receptor flt-1 (VEGFR-1) is a positive modulator of vascular sprout formation and branching morphogenesis. Blood. 2004, 103: 4527-4535. 10.1182/blood-2003-07-2315.CrossRefPubMed Kearney JB, Kappas NC, Ellerstrom C, DiPaola FW, Bautch VL: The VEGF receptor flt-1 (VEGFR-1) is a positive modulator of vascular sprout formation and branching morphogenesis. Blood. 2004, 103: 4527-4535. 10.1182/blood-2003-07-2315.CrossRefPubMed
41.
go back to reference Kappas NC, Zeng G, Chappell JC, Kearney JB, Hazarika S, Kallianos KG, Patterson C, Annex BH, Bautch VL: The VEGF receptor Flt-1 spatially modulates Flk-1 signaling and blood vessel branching. J Cell Biol. 2008, 181: 847-858. 10.1083/jcb.200709114.PubMedCentralCrossRefPubMed Kappas NC, Zeng G, Chappell JC, Kearney JB, Hazarika S, Kallianos KG, Patterson C, Annex BH, Bautch VL: The VEGF receptor Flt-1 spatially modulates Flk-1 signaling and blood vessel branching. J Cell Biol. 2008, 181: 847-858. 10.1083/jcb.200709114.PubMedCentralCrossRefPubMed
42.
go back to reference Roskoski R: Vascular endothelial growth factor (VEGF) signaling in tumor progression. Crit Rev Oncol Hematol. 2007, 62: 179-213. 10.1016/j.critrevonc.2007.01.006.CrossRefPubMed Roskoski R: Vascular endothelial growth factor (VEGF) signaling in tumor progression. Crit Rev Oncol Hematol. 2007, 62: 179-213. 10.1016/j.critrevonc.2007.01.006.CrossRefPubMed
43.
go back to reference Lin MI, Sessa WC: Vascular endothelial growth factor signaling to endothelial nitric oxide synthase: more than a FLeeTing moment. Circ Res. 2006, 99: 666-668. 10.1161/01.RES.0000245430.24075.a4.CrossRefPubMed Lin MI, Sessa WC: Vascular endothelial growth factor signaling to endothelial nitric oxide synthase: more than a FLeeTing moment. Circ Res. 2006, 99: 666-668. 10.1161/01.RES.0000245430.24075.a4.CrossRefPubMed
44.
go back to reference Hashambhoy YL, Chappell JC, Peirce SM, Bautch VL, Mac Gabhann F: Computational modeling of interacting VEGF and soluble VEGF receptor concentration gradients. Front Physiol. 2011, 2: 62-PubMedCentralCrossRefPubMed Hashambhoy YL, Chappell JC, Peirce SM, Bautch VL, Mac Gabhann F: Computational modeling of interacting VEGF and soluble VEGF receptor concentration gradients. Front Physiol. 2011, 2: 62-PubMedCentralCrossRefPubMed
45.
go back to reference Gonzalez-Cruz RD, Fonseca VC, Darling EM: Cellular mechanical properties reflect the differentiation potential of adipose-derived mesenchymal stem cells. Proc Natl Acad Sci U S A. 2012, 109: E1523-E1529. 10.1073/pnas.1120349109.PubMedCentralCrossRefPubMed Gonzalez-Cruz RD, Fonseca VC, Darling EM: Cellular mechanical properties reflect the differentiation potential of adipose-derived mesenchymal stem cells. Proc Natl Acad Sci U S A. 2012, 109: E1523-E1529. 10.1073/pnas.1120349109.PubMedCentralCrossRefPubMed
46.
go back to reference Li H, Zimmerlin L, Marra KG, Donnenberg VS, Donnenberg AD, Rubin JP: Adipogenic potential of adipose stem cell subpopulations. Plast Reconstr Surg. 2011, 128: 663-672. 10.1097/PRS.0b013e318221db33.PubMedCentralCrossRefPubMed Li H, Zimmerlin L, Marra KG, Donnenberg VS, Donnenberg AD, Rubin JP: Adipogenic potential of adipose stem cell subpopulations. Plast Reconstr Surg. 2011, 128: 663-672. 10.1097/PRS.0b013e318221db33.PubMedCentralCrossRefPubMed
47.
go back to reference Miranville A, Heeschen C, Sengenes C, Curat CA, Busse R, Bouloumie A: Improvement of postnatal neovascularization by human adipose tissue-derived stem cells. Circulation. 2004, 110: 349-355. 10.1161/01.CIR.0000135466.16823.D0.CrossRefPubMed Miranville A, Heeschen C, Sengenes C, Curat CA, Busse R, Bouloumie A: Improvement of postnatal neovascularization by human adipose tissue-derived stem cells. Circulation. 2004, 110: 349-355. 10.1161/01.CIR.0000135466.16823.D0.CrossRefPubMed
48.
go back to reference Fischer LJ, McIlhenny S, Tulenko T, Golesorkhi N, Zhang P, Larson R, Lombardi J, Shapiro I, DiMuzio PJ: Endothelial differentiation of adipose-derived stem cells: effects of endothelial cell growth supplement and shear force. J Surg Res. 2009, 152: 157-166. 10.1016/j.jss.2008.06.029.PubMedCentralCrossRefPubMed Fischer LJ, McIlhenny S, Tulenko T, Golesorkhi N, Zhang P, Larson R, Lombardi J, Shapiro I, DiMuzio PJ: Endothelial differentiation of adipose-derived stem cells: effects of endothelial cell growth supplement and shear force. J Surg Res. 2009, 152: 157-166. 10.1016/j.jss.2008.06.029.PubMedCentralCrossRefPubMed
49.
go back to reference Janeczek Portalska K, Leferink A, Groen N, Fernandes H, Moroni L, Van Blitterswijk C, De Boer J: Endothelial differentiation of mesenchymal stromal cells. PLoS One. 2012, 7: e46842-10.1371/journal.pone.0046842.PubMedCentralCrossRefPubMed Janeczek Portalska K, Leferink A, Groen N, Fernandes H, Moroni L, Van Blitterswijk C, De Boer J: Endothelial differentiation of mesenchymal stromal cells. PLoS One. 2012, 7: e46842-10.1371/journal.pone.0046842.PubMedCentralCrossRefPubMed
50.
go back to reference Park IS, Kim SH, Jung Y, Rhie JW: Endothelial differentiation and vasculogenesis induced by three-dimensional adipose-derived stem cells. Anat Rec (Hoboken). 2013, 296: 168-177. 10.1002/ar.22606.CrossRef Park IS, Kim SH, Jung Y, Rhie JW: Endothelial differentiation and vasculogenesis induced by three-dimensional adipose-derived stem cells. Anat Rec (Hoboken). 2013, 296: 168-177. 10.1002/ar.22606.CrossRef
51.
go back to reference De Girolamo L, Lopa S, Arrigoni E, Sartori MF, Baruffaldi Preis FW, Brini AT: Human adipose-derived stem cells isolated from young and elderly women: their differentiation potential and scaffold interaction during in vitro osteoblastic differentiation. Cytotherapy. 2009, 11: 793-803. 10.3109/14653240903079393.CrossRefPubMed De Girolamo L, Lopa S, Arrigoni E, Sartori MF, Baruffaldi Preis FW, Brini AT: Human adipose-derived stem cells isolated from young and elderly women: their differentiation potential and scaffold interaction during in vitro osteoblastic differentiation. Cytotherapy. 2009, 11: 793-803. 10.3109/14653240903079393.CrossRefPubMed
52.
go back to reference Bourin P, Bunnell BA, Casteilla L, Dominici M, Katz AJ, March KL, Redl H, Rubin JP, Yoshimura K, Gimble JM: Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT). Cytotherapy. 2013, 15: 641-648. 10.1016/j.jcyt.2013.02.006.PubMedCentralCrossRefPubMed Bourin P, Bunnell BA, Casteilla L, Dominici M, Katz AJ, March KL, Redl H, Rubin JP, Yoshimura K, Gimble JM: Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT). Cytotherapy. 2013, 15: 641-648. 10.1016/j.jcyt.2013.02.006.PubMedCentralCrossRefPubMed
53.
go back to reference Oskowitz A, McFerrin H, Gutschow M, Carter ML, Pochampally R: Serum-deprived human multipotent mesenchymal stromal cells (MSCs) are highly angiogenic. Stem Cell Res. 2011, 6: 215-225. 10.1016/j.scr.2011.01.004.CrossRefPubMed Oskowitz A, McFerrin H, Gutschow M, Carter ML, Pochampally R: Serum-deprived human multipotent mesenchymal stromal cells (MSCs) are highly angiogenic. Stem Cell Res. 2011, 6: 215-225. 10.1016/j.scr.2011.01.004.CrossRefPubMed
54.
go back to reference Arciniegas E, Frid MG, Douglas IS, Stenmark KR: Perspectives on endothelial-to-mesenchymal transition: potential contribution to vascular remodeling in chronic pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2007, 293: L1-L8. 10.1152/ajplung.00378.2006.CrossRefPubMed Arciniegas E, Frid MG, Douglas IS, Stenmark KR: Perspectives on endothelial-to-mesenchymal transition: potential contribution to vascular remodeling in chronic pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2007, 293: L1-L8. 10.1152/ajplung.00378.2006.CrossRefPubMed
55.
56.
go back to reference Prockop DJ, Kota DJ, Bazhanov N, Reger RL: Evolving paradigms for repair of tissues by adult stem/progenitor cells (MSCs). J Cell Mol Med. 2010, 14: 2190-2199. 10.1111/j.1582-4934.2010.01151.x.PubMedCentralCrossRefPubMed Prockop DJ, Kota DJ, Bazhanov N, Reger RL: Evolving paradigms for repair of tissues by adult stem/progenitor cells (MSCs). J Cell Mol Med. 2010, 14: 2190-2199. 10.1111/j.1582-4934.2010.01151.x.PubMedCentralCrossRefPubMed
57.
go back to reference Yang D, Wang W, Li L, Peng Y, Chen P, Huang H, Guo Y, Xia X, Wang Y, Wang H: The relative contribution of paracine effect versus direct differentiation on adipose-derived stem cell transplantation mediated cardiac repair. PLoS One. 2013, 8: e59020-10.1371/journal.pone.0059020.PubMedCentralCrossRefPubMed Yang D, Wang W, Li L, Peng Y, Chen P, Huang H, Guo Y, Xia X, Wang Y, Wang H: The relative contribution of paracine effect versus direct differentiation on adipose-derived stem cell transplantation mediated cardiac repair. PLoS One. 2013, 8: e59020-10.1371/journal.pone.0059020.PubMedCentralCrossRefPubMed
58.
go back to reference Levi B, Nelson ER, Hyun JS, Glotzbach JP, Li S, Nauta A, Montoro DT, Lee M, Commons GC, Hu S: Enhancement of human adipose-derived stromal cell angiogenesis through knockdown of a BMP-2 inhibitor. Plast Reconstr Surg. 2012, 129: 53-66. 10.1097/PRS.0b013e3182361ff5.PubMedCentralCrossRefPubMed Levi B, Nelson ER, Hyun JS, Glotzbach JP, Li S, Nauta A, Montoro DT, Lee M, Commons GC, Hu S: Enhancement of human adipose-derived stromal cell angiogenesis through knockdown of a BMP-2 inhibitor. Plast Reconstr Surg. 2012, 129: 53-66. 10.1097/PRS.0b013e3182361ff5.PubMedCentralCrossRefPubMed
59.
go back to reference Yan A, Avraham T, Zampell JC, Haviv YS, Weitman E, Mehrara BJ: Adipose-derived stem cells promote lymphangiogenesis in response to VEGF-C stimulation or TGF-beta1 inhibition. Future Oncol. 2011, 7: 1457-1473. 10.2217/fon.11.121.PubMedCentralCrossRefPubMed Yan A, Avraham T, Zampell JC, Haviv YS, Weitman E, Mehrara BJ: Adipose-derived stem cells promote lymphangiogenesis in response to VEGF-C stimulation or TGF-beta1 inhibition. Future Oncol. 2011, 7: 1457-1473. 10.2217/fon.11.121.PubMedCentralCrossRefPubMed
Metadata
Title
Identical effects of VEGF and serum-deprivation on phenotype and function of adipose-derived stromal cells from healthy donors and patients with ischemic heart disease
Authors
Bjarke Follin
Josefine Tratwal
Mandana Haack-Sørensen
Jens Jørgen Elberg
Jens Kastrup
Annette Ekblond
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2013
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/1479-5876-11-219

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