Circulation. 2003;108:2070-2073
Published online before print October 20, 2003, doi: 10.1161/01.CIR.0000099501.52718.70
Published online before print October 20, 2003, doi: 10.1161/01.CIR.0000099501.52718.70
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2003;108:2070.)
© 2003 American Heart Association, Inc.
Brief Rapid Communications |
Transdifferentiation of Human Peripheral Blood CD34+-Enriched Cell Population Into Cardiomyocytes, Endothelial Cells, and Smooth Muscle Cells In Vivo
From Departments of Cardiology (E.T.H.Y., S.Z.), Blood and Marrow Transplantation (M.K.), and Bioimmunotherapy (Z.E.), The University of Texas–M.D. Anderson Cancer Center; The University of Texas Houston Health Science Center (E.T.H.Y., H.D.W., J.T.W.); and the Texas Heart Institute, St Luke’s Episcopal Hospital (E.T.H.Y., J.T.W.), Houston, Tex.
Correspondence to Edward T.H. Yeh, MD, 1515 Holcombe Blvd, Box 449, Houston, TX 77030-4095. E-mail etyeh{at}mdanderson.org
Received April 3, 2003; de novo received July 7, 2003; revision received September 3, 2003; accepted September 8, 2003.
Background— Adult human peripheral blood cells have been shown to differentiate into mature cells of nonhematopoietic tissues, such as hepatocytes and epithelial cells of the skin and gastrointestinal track. We investigated whether these cells could also transdifferentiate into human cardiomyocytes, mature endothelial cells, and smooth muscle cells in vivo.
Methods and Results— Myocardial infarction was created in SCID mice by occluding the left anterior descending coronary artery, after which adult peripheral blood CD34+ cells were injected into the tail vein. Hearts were harvested 2 months after injection and stained for human leukocyte antigen (HLA) and markers for cardiomyocytes, endothelial cells, and smooth muscle cells. Cardiomyocytes, endothelial cells, and smooth muscle cells that bear HLA were identified in the infarct and peri-infarct regions of the mouse hearts. In a separate experiment, CD34+ cells were injected intraventricularly into mice without experimental myocardial infarction. HLA-positive myocytes and smooth muscle cells could only be identified in 1 of these mice killed at different time points.
Conclusions— Adult peripheral blood CD34+ cells can transdifferentiate into cardiomyocytes, mature endothelial cells, and smooth muscle cells in vivo. However, transdifferentiation is augmented significantly by local tissue injury. The use of peripheral blood CD34+ cells for cell-based therapy should greatly simplify the procurement of cells for the regeneration of damaged myocardium.
Key Words: cells • muscle, smooth • endothelium • myocyte
This article has been cited by other articles:
 |
|
 |
|
  K. V Arom, P. Ruengsakulrach, M. Belkin, and M. Tiensuwan Intramyocardial Angiogenic Cell Precursors in Nonischemic Dilated Cardiomyopathy Asian Cardiovasc Thorac Ann, August 1, 2009; 17(4): 382 - 388. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. K. Kim, H.-N. Pak, J. H. Park, J. I. Choi, M.-H. Nam, Y. Jo, and Y.-H. Kim Non-ischaemic titrated cardiac injury caused by radiofrequency catheter ablation of atrial fibrillation mobilizes CD34-positive mononuclear cells by non-stromal cell-derived factor-1{alpha} mechanism Europace, August 1, 2009; 11(8): 1024 - 1031. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. D. Boudoulas and A. K. Hatzopoulos Cardiac repair and regeneration: the Rubik's cube of cell therapy for heart disease Dis. Model. Mech., July 1, 2009; 2(7-8): 344 - 358. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Yamahara and H. Itoh Potential use of endothelial progenitor cells for regeneration of the vasculature Therapeutic Advances in Cardiovascular Disease, February 1, 2009; 3(1): 17 - 27. [Abstract] [PDF]
|
|
|
|
 |
|
 M. Valgimigli, G. G.L. Biondi-Zoccai, P. Malagutti, A. M. Leone, and A. Abbate Autologous bone marrow stem cell mobilization induced by granulocyte colony-stimulating factor after myocardial infarction Eur. Heart J. Suppl., December 1, 2008; 10(suppl_K): K27 - K34. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Murasawa and T. Asahara Review: Cardiogenic potential of endothelial progenitor cells Therapeutic Advances in Cardiovascular Disease, October 1, 2008; 2(5): 341 - 348. [Abstract] [PDF]
|
|
|
|
 |
|
 H. Kubo, N. Jaleel, A. Kumarapeli, R. M. Berretta, G. Bratinov, X. Shan, H. Wang, S. R. Houser, and K. B. Margulies Increased Cardiac Myocyte Progenitors in Failing Human Hearts Circulation, August 5, 2008; 118(6): 649 - 657. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. W. Stone Angioplasty Strategies in ST-Segment-Elevation Myocardial Infarction: Part II: Intervention After Fibrinolytic Therapy, Integrated Treatment Recommendations, and Future Directions Circulation, July 29, 2008; 118(5): 552 - 566. [Full Text] [PDF]
|
|
|
|
 |
|
 T. C. Zhao, A. Tseng, N. Yano, Y. Tseng, P. A. Davol, R. J. Lee, L. G. Lum, and J. F. Padbury Targeting human CD34+ hematopoietic stem cells with anti-CD45 x anti-myosin light-chain bispecific antibody preserves cardiac function in myocardial infarction J Appl Physiol, June 1, 2008; 104(6): 1793 - 1800. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Zampetaki, J. P. Kirton, and Q. Xu Vascular repair by endothelial progenitor cells Cardiovasc Res, June 1, 2008; 78(3): 413 - 421. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H Ince, M Valgimigli, M Petzsch, J S. de Lezo, F Kuethe, S Dunkelmann, G Biondi-Zoccai, and C A Nienaber Cardiovascular events and re-stenosis following administration of G-CSF in acute myocardial infarction: systematic review and meta-analysis Heart, May 1, 2008; 94(5): 610 - 616. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. V Arom, P. Ruengsakulrach, and V. Jotisakulratana Intramyocardial Angiogenic Cell Precursor Injection for Cardiomyopathy Asian Cardiovasc Thorac Ann, April 1, 2008; 16(2): 143 - 148. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Orlandi, F. Pagani, D. Avitabile, G. Bonanno, G. Scambia, E. Vigna, F. Grassi, F. Eusebi, S. Fucile, M. Pesce, et al. Functional properties of cells obtained from human cord blood CD34+ stem cells and mouse cardiac myocytes in coculture Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1541 - H1549. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Atluri, C. M. Panlilio, G. P. Liao, E. E. Suarez, R. C. McCormick, W. Hiesinger, J. E. Cohen, M. J. Smith, A. B. Patel, W. Feng, et al. Transmyocardial revascularization to enhance myocardial vasculogenesis and hemodynamic function. J. Thorac. Cardiovasc. Surg., February 1, 2008; 135(2): 283 - 291. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. T. Gerthoffer Migration of Airway Smooth Muscle Cells Proceedings of the ATS, January 1, 2008; 5(1): 97 - 105. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Lipinski, G. G.L. Biondi-Zoccai, A. Abbate, R. Khianey, I. Sheiban, J. Bartunek, M. Vanderheyden, H.-S. Kim, H.-J. Kang, B. E. Strauer, et al. Impact of Intracoronary Cell Therapy on Left Ventricular Function in the Setting of Acute Myocardial Infarction: A Collaborative Systematic Review and Meta-Analysis of Controlled Clinical Trials J. Am. Coll. Cardiol., October 30, 2007; 50(18): 1761 - 1767. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Leor, S. Gerecht, S. Cohen, L. Miller, R. Holbova, A. Ziskind, M. Shachar, M. S Feinberg, E. Guetta, and J. Itskovitz-Eldor Human embryonic stem cell transplantation to repair the infarcted myocardium Heart, October 1, 2007; 93(10): 1278 - 1284. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. S. Ferreira, S. Gerecht, H. F. Shieh, N. Watson, M. A. Rupnick, S. M. Dallabrida, G. Vunjak-Novakovic, and R. Langer Vascular Progenitor Cells Isolated From Human Embryonic Stem Cells Give Rise to Endothelial and Smooth Muscle Like Cells and Form Vascular Networks In Vivo Circ. Res., August 3, 2007; 101(3): 286 - 294. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Grote, G. Salguero, M. Ballmaier, M. Dangers, H. Drexler, and B. Schieffer The angiogenic factor CCN1 promotes adhesion and migration of circulating CD34+ progenitor cells: potential role in angiogenesis and endothelial regeneration Blood, August 1, 2007; 110(3): 877 - 885. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. T. Gerthoffer Mechanisms of Vascular Smooth Muscle Cell Migration Circ. Res., March 16, 2007; 100(5): 607 - 621. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Zhang, E. Shpall, J. T. Willerson, and E. T.H. Yeh Fusion of Human Hematopoietic Progenitor Cells and Murine Cardiomyocytes Is Mediated by {alpha}4{beta}1 Integrin/Vascular Cell Adhesion Molecule-1 Interaction Circ. Res., March 16, 2007; 100(5): 693 - 702. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Matsumoto, A. Kawamoto, R. Kuroda, M. Ishikawa, Y. Mifune, H. Iwasaki, M. Miwa, M. Horii, S. Hayashi, A. Oyamada, et al. Therapeutic Potential of Vasculogenesis and Osteogenesis Promoted by Peripheral Blood CD34-Positive Cells for Functional Bone Healing Am. J. Pathol., October 1, 2006; 169(4): 1440 - 1457. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Lunde, S. Solheim, S. Aakhus, H. Arnesen, M. Abdelnoor, T. Egeland, K. Endresen, A. Ilebekk, A. Mangschau, J. G. Fjeld, et al. Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N. Engl. J. Med., September 21, 2006; 355(12): 1199 - 1209. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-H. Wang, N. Anderson, S.-H. Li, P. E. Szmitko, W.-J. Cherng, P. W.M. Fedak, S. Fazel, R.-K. Li, T. M. Yau, R. D. Weisel, et al. Stem Cell Factor Deficiency Is Vasculoprotective: Unraveling a New Therapeutic Potential of Imatinib Mesylate Circ. Res., September 15, 2006; 99(6): 617 - 625. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. P. Fadini, S. V. de Kreutzenberg, A. Coracina, I. Baesso, C. Agostini, A. Tiengo, and A. Avogaro Circulating CD34+ cells, metabolic syndrome, and cardiovascular risk Eur. Heart J., September 2, 2006; 27(18): 2247 - 2255. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Misao, G. Takemura, M. Arai, T. Ohno, H. Onogi, T. Takahashi, S. Minatoguchi, T. Fujiwara, and H. Fujiwara Importance of recruitment of bone marrow-derived CXCR4+ cells in post-infarct cardiac repair mediated by G-CSF Cardiovasc Res, August 1, 2006; 71(3): 455 - 465. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. W. Serruys Fourth Annual American College of Cardiology International Lecture: A Journey in the Interventional Field J. Am. Coll. Cardiol., May 2, 2006; 47(9): 1754 - 1768. [Full Text] [PDF]
|
|
|
|
 |
|
 O. Awad, E. I. Dedkov, C. Jiao, S. Bloomer, R. J. Tomanek, and G. C. Schatteman Differential Healing Activities of CD34+ and CD14+ Endothelial Cell Progenitors Arterioscler Thromb Vasc Biol, April 1, 2006; 26(4): 758 - 764. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Iwasaki, A. Kawamoto, M. Ishikawa, A. Oyamada, S. Nakamori, H. Nishimura, K. Sadamoto, M. Horii, T. Matsumoto, S. Murasawa, et al. Dose-Dependent Contribution of CD34-Positive Cell Transplantation to Concurrent Vasculogenesis and Cardiomyogenesis for Functional Regenerative Recovery After Myocardial Infarction Circulation, March 14, 2006; 113(10): 1311 - 1325. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Anghelina, P. Krishnan, L. Moldovan, and N. I. Moldovan Monocytes/Macrophages Cooperate with Progenitor Cells during Neovascularization and Tissue Repair: Conversion of Cell Columns into Fibrovascular Bundles Am. J. Pathol., February 1, 2006; 168(2): 529 - 541. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Boxall, S. T. Holgate, and D. E. Davies The contribution of transforming growth factor-{beta} and epidermal growth factor signalling to airway remodelling in chronic asthma Eur. Respir. J., January 1, 2006; 27(1): 208 - 229. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. M. Howson, A. C. Aplin, M. Gelati, G. Alessandri, E. A. Parati, and R. F. Nicosia The postnatal rat aorta contains pericyte progenitor cells that form spheroidal colonies in suspension culture Am J Physiol Cell Physiol, December 1, 2005; 289(6): C1396 - C1407. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ince, M. Petzsch, H. D. Kleine, H. Schmidt, T. Rehders, T. Korber, C. Schumichen, M. Freund, and C. A. Nienaber Preservation From Left Ventricular Remodeling by Front-Integrated Revascularization and Stem Cell Liberation in Evolving Acute Myocardial Infarction by Use of Granulocyte-Colony-Stimulating Factor (FIRSTLINE-AMI) Circulation, November 15, 2005; 112(20): 3097 - 3106. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. Willerson, E. T.H. Yeh, Y.-J. Geng, and E. C. Perin Blood-Derived Progenitor Cells After Recanalization of Chronic Coronary Artery Occlusions in Humans Circ. Res., October 14, 2005; 97(8): 735 - 736. [Full Text] [PDF]
|
|
|
|
|
|
S. Erbs, A. Linke, V. Adams, K. Lenk, H. Thiele, K.-W. Diederich, F. Emmrich, R. Kluge, K. Kendziorra, O. Sabri, et al. Transplantation of Blood-Derived Progenitor Cells After Recanalization of Chronic Coronary Artery Occlusion: First Randomized and Placebo-Controlled Study Circ. Res., October 14, 2005; 97(8): 756 - 762. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. T. Chan, S. H. Li, and S. Verma Nocturnal hemodialysis is associated with restoration of impaired endothelial progenitor cell biology in end-stage renal disease Am J Physiol Renal Physiol, October 1, 2005; 289(4): F679 - F684. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Valgimigli, G. M. Rigolin, C. Cittanti, P. Malagutti, S. Curello, G. Percoco, A. M. Bugli, M. D. Porta, L. Z. Bragotti, L. Ansani, et al. Use of granulocyte-colony stimulating factor during acute myocardial infarction to enhance bone marrow stem cell mobilization in humans: clinical and angiographic safety profile Eur. Heart J., September 2, 2005; 26(18): 1838 - 1845. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Roy-Chaudhury Endothelial Progenitor Cells, Neointimal Hyperplasia, and Hemodialysis Vascular Access Dysfunction: Novel Therapies for a Recalcitrant Clinical Problem Circulation, July 5, 2005; 112(1): 3 - 5. [Full Text] [PDF]
|
|
|
|
|
|
J. I. Rotmans, J. M.M. Heyligers, H. J.M. Verhagen, E. Velema, M. M. Nagtegaal, D. P.V. de Kleijn, F. G. de Groot, E. S.G. Stroes, and G. Pasterkamp In Vivo Cell Seeding With Anti-CD34 Antibodies Successfully Accelerates Endothelialization but Stimulates Intimal Hyperplasia in Porcine Arteriovenous Expanded Polytetrafluoroethylene Grafts Circulation, July 5, 2005; 112(1): 12 - 18. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Murasawa, A. Kawamoto, M. Horii, S. Nakamori, and T. Asahara Niche-Dependent Translineage Commitment of Endothelial Progenitor Cells, Not Cell Fusion in General, Into Myocardial Lineage Cells Arterioscler Thromb Vasc Biol, July 1, 2005; 25(7): 1388 - 1394. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Leone, S. Rutella, G. Bonanno, A. Abbate, A. G. Rebuzzi, S. Giovannini, M. Lombardi, L. Galiuto, G. Liuzzo, F. Andreotti, et al. Mobilization of bone marrow-derived stem cells after myocardial infarction and left ventricular function Eur. Heart J., June 2, 2005; 26(12): 1196 - 1204. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. K. Haider and M. Ashraf Bone marrow stem cell transplantation for cardiac repair Am J Physiol Heart Circ Physiol, June 1, 2005; 288(6): H2557 - H2567. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Koyanagi, R. P. Brandes, J. Haendeler, A. M. Zeiher, and S. Dimmeler Cell-to-Cell Connection of Endothelial Progenitor Cells With Cardiac Myocytes by Nanotubes: A Novel Mechanism for Cell Fate Changes? Circ. Res., May 27, 2005; 96(10): 1039 - 1041. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Koyanagi, J. Haendeler, C. Badorff, R. P. Brandes, J. Hoffmann, P. Pandur, A. M. Zeiher, M. Kuhl, and S. Dimmeler Non-canonical Wnt Signaling Enhances Differentiation of Human Circulating Progenitor Cells to Cardiomyogenic Cells J. Biol. Chem., April 29, 2005; 280(17): 16838 - 16842. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M. Humpert, R. Neuwirth, M. J. Battista, O. Voronko, M. von Eynatten, I. Konrade, G. Rudofsky Jr, T. Wendt, A. Hamann, M. Morcos, et al. SDF-1 Genotype Influences Insulin-Dependent Mobilization of Adult Progenitor Cells in Type 2 Diabetes Diabetes Care, April 1, 2005; 28(4): 934 - 936. [Full Text] [PDF]
|
|
|
|
|
|
K. C. Wollert and H. Drexler Clinical Applications of Stem Cells for the Heart Circ. Res., February 4, 2005; 96(2): 151 - 163. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Zhang, D. Wang, Z. Estrov, S. Raj, J. T. Willerson, and E. T.H. Yeh Both Cell Fusion and Transdifferentiation Account for the Transformation of Human Peripheral Blood CD34-Positive Cells Into Cardiomyocytes In Vivo Circulation, December 21, 2004; 110(25): 3803 - 3807. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Regula, M. J. Rzeszutek, D. Baetz, C. Seneviratne, and L. A. Kirshenbaum Therapeutic opportunities for cell cycle re-entry and cardiac regeneration Cardiovasc Res, December 1, 2004; 64(3): 395 - 401. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Abbott, Y. Huang, D. Liu, R. Hickey, D. S. Krause, and F. J. Giordano Stromal Cell-Derived Factor-1{alpha} Plays a Critical Role in Stem Cell Recruitment to the Heart After Myocardial Infarction but Is Not Sufficient to Induce Homing in the Absence of Injury Circulation, November 23, 2004; 110(21): 3300 - 3305. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Sho, M. Sho, H. Nanjo, K. Kawamura, H. Masuda, and R. L. Dalman Hemodynamic Regulation of CD34+ Cell Localization and Differentiation in Experimental Aneurysms Arterioscler Thromb Vasc Biol, October 1, 2004; 24(10): 1916 - 1921. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Dimmeler and A. M. Zeiher Wanted! The best cell for cardiac regeneration J. Am. Coll. Cardiol., July 21, 2004; 44(2): 464 - 466. [Full Text] [PDF]
|
|