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Blood, 1 March 2004, Vol. 103, No. 5, pp. 1669-1675.
Prepublished online as a Blood First Edition Paper on October 23, 2003; DOI 10.1182/blood-2003-05-1670.
Previous Article | Table of Contents | Next Article 
HEMATOPOIESIS
Isolation of multipotent mesenchymal stem cells from umbilical cord blood
Oscar K. Lee,
Tom K. Kuo,
Wei-Ming Chen,
Kuan-Der Lee,
Shie-Liang Hsieh, and
Tain-Hsiung Chen
From the Department of Orthopaedics and Traumatology, Veterans General Hospital-Taipei, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan; Cancer Research Division, National Health Research Institute, Taipei, Taiwan; and Department of Immunology, National Yang-Ming University, Taipei, Taiwan.
It is well accepted that umbilical cord blood has been a source for hematopoietic stem cells. However, controversy exists as to whether cord blood can serve as a source of mesenchymal stem cells, which can differentiate into cells of different connective tissue lineages such as bone, cartilage, and fat, and little success has been reported in the literature about the isolation of such cells from cord blood. Here we report a novel method to obtain single cell-derived, clonally expanded mesenchymal stem cells that are of multilineage differentiation potential by negative immunoselection and limiting dilution. The immunophenotype of these clonally expanded cells is consistent with that reported for bone marrow mesenchymal stem cells. Under appropriate induction conditions, these cells can differentiate into bone, cartilage, and fat. Surprisingly, these cells were also able to differentiate into neuroglial- and hepatocyte-like cells under appropriate induction conditions and, thus, these cells may be more than mesenchymal stem cells as evidenced by their ability to differentiate into cell types of all 3 germ layers. In conclusion, umbilical cord blood does contain mesenchymal stem cells and should not be regarded as medical waste. It can serve as an alternative source of mesenchymal stem cells to bone marrow.

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|
 |
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|
 |

|
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|
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|

|
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|
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|
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|
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|
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|
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|
 |
|

|
 |

|
 |
 
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|
 |
|

|
 |

|
 |
 
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26(7):
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|
 |
|

|
 |

|
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|
 |
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|
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|
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|
 |
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|
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|
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[Full Text]
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|
 |
|

|
 |

|
 |
 
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|
 |
|

|
 |

|
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|
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|
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|
 |
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|
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|
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|
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|
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|
 |
|

|
 |

|
 |
 
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|
 |
|

|
 |

|
 |
 
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|
 |
|

|
 |

|
 |
 
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25(11):
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[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Functional Network Analysis of the Transcriptomes of Mesenchymal Stem Cells Derived from Amniotic Fluid, Amniotic Membrane, Cord Blood, and Bone Marrow
Stem Cells,
October 1, 2007;
25(10):
2511 - 2523.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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The Significant Cardiomyogenic Potential of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells In Vitro
Stem Cells,
August 1, 2007;
25(8):
2017 - 2024.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. S. Park, K. H. Jung, S. H. Kim, K. S. Kim, M. R. Choi, Y. Kim, and Y. G. Chai
Functional Expression of Ion Channels in Mesenchymal Stem Cells Derived from Umbilical Cord Vein
Stem Cells,
August 1, 2007;
25(8):
2044 - 2052.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. E. Gargett
Review Article: Stem Cells in Human Reproduction
Reproductive Sciences,
July 1, 2007;
14(5):
405 - 424.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
S. A. Kuznetsov, M. H. Mankani, A. I. Leet, N. Ziran, S. Gronthos, and P. G. Robey
Circulating Connective Tissue Precursors: Extreme Rarity in Humans and Chondrogenic Potential in Guinea Pigs
Stem Cells,
July 1, 2007;
25(7):
1830 - 1839.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C.-Y. Lien, O. K. Lee, and Y. Su
Cbfb Enhances the Osteogenic Differentiation of Both Human and Mouse Mesenchymal Stem Cells Induced by Cbfa-1 via Reducing Its Ubiquitination-Mediated Degradation
Stem Cells,
June 1, 2007;
25(6):
1462 - 1468.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
I. Aurich, L. P Mueller, H. Aurich, J. Luetzkendorf, K. Tisljar, M. M Dollinger, W. Schormann, J. Walldorf, J. G Hengstler, W. E Fleig, et al.
Functional integration of hepatocytes derived from human mesenchymal stem cells into mouse livers
Gut,
March 1, 2007;
56(3):
405 - 415.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. W. Christopherson, T. Bakhshi, S. Bodie, S. Kidd, R. Zabriskie, and S. Ramin
Mesenchymal Stem Cells from the Wharton's Jelly of Umbilical Cord Segments Support the Maintenance of Long Term Culture-Initiating Cells from Cord Blood.
Blood (ASH Annual Meeting Abstracts),
November 16, 2006;
108(11):
3650 - 3650.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
K. H. Wu, Y. L. Liu, B. Zhou, and Z. C. Han
Cellular therapy and myocardial tissue engineering: the role of adult stem and progenitor cells
Eur. J. Cardiothorac. Surg.,
November 1, 2006;
30(5):
770 - 781.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. Y. Rochefort, B. Delorme, A. Lopez, O. Herault, P. Bonnet, P. Charbord, V. Eder, and J. Domenech
Multipotential Mesenchymal Stem Cells Are Mobilized into Peripheral Blood by Hypoxia
Stem Cells,
October 1, 2006;
24(10):
2202 - 2208.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. Yazawa, T. Mizutani, K. Yamada, H. Kawata, T. Sekiguchi, M. Yoshino, T. Kajitani, Z. Shou, A. Umezawa, and K. Miyamoto
Differentiation of Adult Stem Cells Derived from Bone Marrow Stroma into Leydig or Adrenocortical Cells
Endocrinology,
September 1, 2006;
147(9):
4104 - 4111.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
X. Wang, F. Li, and C. Niyibizi
Progenitors Systemically Transplanted into Neonatal Mice Localize to Areas of Active Bone Formation In Vivo: Implications of Cell Therapy for Skeletal Diseases
Stem Cells,
August 1, 2006;
24(8):
1869 - 1878.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Koerner, D. Nesic, J. D. Romero, W. Brehm, P. Mainil-Varlet, and S. P. Grogan
Equine peripheral blood-derived progenitors in comparison to bone marrow-derived mesenchymal stem cells.
Stem Cells,
June 1, 2006;
24(6):
1613 - 1619.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B.-R. Son, L. A. Marquez-Curtis, M. Kucia, M. Wysoczynski, A. R. Turner, J. Ratajczak, M. Z. Ratajczak, and A. Janowska-Wieczorek
Migration of Bone Marrow and Cord Blood Mesenchymal Stem Cells In Vitro Is Regulated by Stromal-Derived Factor-1-CXCR4 and Hepatocyte Growth Factor-c-met Axes and Involves Matrix Metalloproteinases
Stem Cells,
May 1, 2006;
24(5):
1254 - 1264.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Kern, H. Eichler, J. Stoeve, H. Kluter, and K. Bieback
Comparative Analysis of Mesenchymal Stem Cells from Bone Marrow, Umbilical Cord Blood, or Adipose Tissue
Stem Cells,
May 1, 2006;
24(5):
1294 - 1301.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. L. Weiss, S. Medicetty, A. R. Bledsoe, R. S. Rachakatla, M. Choi, S. Merchav, Y. Luo, M. S. Rao, G. Velagaleti, and D. Troyer
Human Umbilical Cord Matrix Stem Cells: Preliminary Characterization and Effect of Transplantation in a Rodent Model of Parkinson's Disease
Stem Cells,
March 1, 2006;
24(3):
781 - 792.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M.-S. Tsai, S.-M. Hwang, Y.-L. Tsai, F.-C. Cheng, J.-L. Lee, and Y.-J. Chang
Clonal Amniotic Fluid-Derived Stem Cells Express Characteristics of Both Mesenchymal and Neural Stem Cells
Biol Reprod,
March 1, 2006;
74(3):
545 - 551.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. Tondreau, N. Meuleman, A. Delforge, M. Dejeneffe, R. Leroy, M. Massy, C. Mortier, D. Bron, and L. Lagneaux
Mesenchymal Stem Cells Derived from CD133-Positive Cells in Mobilized Peripheral Blood and Cord Blood: Proliferation, Oct4 Expression, and Plasticity
Stem Cells,
September 1, 2005;
23(8):
1105 - 1112.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. R. Fuchs, D. Hannouche, S. Terada, S. Zand, J. P. Vacanti, and D. O. Fauza
Cartilage Engineering from Ovine Umbilical Cord Blood Mesenchymal Progenitor Cells
Stem Cells,
August 1, 2005;
23(7):
958 - 964.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Sato, H. Araki, J. Kato, K. Nakamura, Y. Kawano, M. Kobune, T. Sato, K. Miyanishi, T. Takayama, M. Takahashi, et al.
Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion
Blood,
July 15, 2005;
106(2):
756 - 763.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Zipori
The Stem State: Plasticity Is Essential, Whereas Self-Renewal and Hierarchy Are Optional
Stem Cells,
June 1, 2005;
23(6):
719 - 726.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. A. Jeong, S. H. Hong, E. J. Gang, C. Ahn, S. H. Hwang, I. H. Yang, H. Han, and H. Kim
Differential Gene Expression Profiling of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells by DNA Microarray
Stem Cells,
April 1, 2005;
23(4):
584 - 593.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Terai, T. Uyama, T. Sugiki, X.-K. Li, A. Umezawa, and T. Kiyono
Immortalization of Human Fetal Cells: The Life Span of Umbilical Cord Blood-derived Cells Can Be Prolonged without Manipulating p16INK4a/RB Braking Pathway
Mol. Biol. Cell,
March 1, 2005;
16(3):
1491 - 1499.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. L. Yen, H.-I Huang, C.-C. Chien, H.-Y. Jui, B.-S. Ko, M. Yao, C.-T. Shun, M.-l. Yen, M.-C. Lee, and Y.-C. Chen
Isolation of Multipotent Cells from Human Term Placenta
Stem Cells,
January 1, 2005;
23(1):
3 - 9.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. A. Panepucci, J. L.C. Siufi, W. A. Silva Jr., R. Proto-Siquiera, L. Neder, M. Orellana, V. Rocha, D. T. Covas, and M. A. Zago
Comparison of Gene Expression of Umbilical Cord Vein and Bone Marrow-Derived Mesenchymal Stem Cells
Stem Cells,
December 1, 2004;
22(7):
1263 - 1278.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|
|