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MBC in Press, published online ahead of print September 24, 2002
Mol. Biol. Cell 10.1091/mbc.E02-02-0105

A more recent version of this article appeared on December 1, 2002
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Submitted on February 25, 2002
Revised on June 21, 2002
Accepted on August 23, 2002

HUMAN ADIPOSE TISSUE IS A SOURCE OF MULTIPOTENT STEM CELLS

Patricia A. Zuk1*, Min Zhu2, Peter Ashjian2, Daniel A. De Ugarte2, Jerry I. Huang2, Hiroshi Mizuno2, Zeni C. Alfonso2, John K. Fraser2, Prosper Benhaim2, and Marc H. Hedrick2

1 Regenerative Bioengineering and Repair Laboratory, UCLA School of Medicine, Departments of Surgery and Orthopedics, Los Angeles, CA 90095
2 Regenerative Bioengineering and Repair Laboratory, UCLA School of Medicine, Departments of Surgery and Orthopedics, Los Angeles, CA 90095

* Corresponding author. E-mail address: zukpat{at}yahoo.com.

Much of the work conducted on adult stem cells has focused on mesenchymal stem cells (MSCs) found within the bone marrow stroma. Adipose tissue, like bone marrow, is derived from the embryonic mesenchyme and contains a stroma that is easily isolated. Preliminary studies have recently identified a putative stem cell population within the adipose stromal compartment. This cell population, termed Processed Lipoaspirate (PLA) cells, can be isolated from human lipoaspirates and, like MSCs, differentiate toward the osteogenic, adipogenic, myogenic and chondrogenic lineages. To confirm if adipose tissue contains stem cells, the PLA population and multiple clonal isolates were analyzed using several molecular and biochemical approaches. PLA cells expressed multiple CD marker antigens similar to those observed on MSCs. Mesodermal lineage induction of PLA cells and clones resulted in the expression of multiple lineage-specific genes and proteins. Furthermore, biochemical analysis also confirmed lineage-specific activity. In addition to mesodermal capacity, PLA cells and clones differentiated into putative neurogenic cells, exhibiting a neuronal-like morphology and expressing several proteins consistent with the neuronal phenotype. Finally, PLA cells exhibited unique characteristics distinct from those seen in MSCs, including differences in CD marker profile and gene expression.




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Mol. Cell. ProteomicsHome page
J. P. DeLany, Z. E. Floyd, S. Zvonic, A. Smith, A. Gravois, E. Reiners, X. Wu, G. Kilroy, M. Lefevre, and J. M. Gimble
Proteomic Analysis of Primary Cultures of Human Adipose-derived Stem Cells: Modulation by Adipogenesis
Mol. Cell. Proteomics, June 1, 2005; 4(6): 731 - 740.
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JEMHome page
A.-M. Rodriguez, D. Pisani, C. A. Dechesne, C. Turc-Carel, J.-Y. Kurzenne, B. Wdziekonski, A. Villageois, C. Bagnis, J.-P. Breittmayer, H. Groux, et al.
Transplantation of a multipotent cell population from human adipose tissue induces dystrophin expression in the immunocompetent mdx mouse
J. Exp. Med., May 2, 2005; 201(9): 1397 - 1405.
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Mol. Biol. CellHome page
A. C. Boquest, A. Shahdadfar, K. Fronsdal, O. Sigurjonsson, S. H. Tunheim, P. Collas, and J. E. Brinchmann
Isolation and Transcription Profiling of Purified Uncultured Human Stromal Stem Cells: Alteration of Gene Expression after In Vitro Cell Culture
Mol. Biol. Cell, March 1, 2005; 16(3): 1131 - 1141.
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INT J SURG PATHOLHome page
P. Pytel, J. B. Taxy, and T. Krausz
Divergent Differentiation In Malignant Soft Tissue Neoplasms: The Paradigm of Liposarcoma and Malignant Peripheral Nerve Sheath Tumor
International Journal of Surgical Pathology, January 1, 2005; 13(1): 19 - 28.
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Mol. Biol. CellHome page
S. Aoki, S. Toda, T. Ando, and H. Sugihara
Bone Marrow Stromal Cells, Preadipocytes, and Dermal Fibroblasts Promote Epidermal Regeneration in Their Distinctive Fashions
Mol. Biol. Cell, October 1, 2004; 15(10): 4647 - 4657.
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J. Cell Sci.Home page
S. K. Kang, L. A. Putnam, J. Ylostalo, I. R. Popescu, J. Dufour, A. Belousov, and B. A. Bunnell
Neurogenesis of Rhesus adipose stromal cells
J. Cell Sci., August 15, 2004; 117(18): 4289 - 4299.
[Abstract] [Full Text] [PDF]


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CirculationHome page
A. Miranville, C. Heeschen, C. Sengenes, C.A. Curat, R. Busse, and A. Bouloumie
Improvement of Postnatal Neovascularization by Human Adipose Tissue-Derived Stem Cells
Circulation, July 20, 2004; 110(3): 349 - 355.
[Abstract] [Full Text] [PDF]


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Circ. Res.Home page
M. F. Pittenger and B. J. Martin
Mesenchymal Stem Cells and Their Potential as Cardiac Therapeutics
Circ. Res., July 9, 2004; 95(1): 9 - 20.
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Nephrol Dial TransplantHome page
J. Honold, B. Assmus, R. Lehman, A. M. Zeiher, and S. Dimmeler
Stem cell therapy of cardiac disease: an update
Nephrol. Dial. Transplant., July 1, 2004; 19(7): 1673 - 1677.
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Toxicol SciHome page
J. C. Davila, G. G. Cezar, M. Thiede, S. Strom, T. Miki, and J. Trosko
Use and Application of Stem Cells in Toxicology
Toxicol. Sci., June 1, 2004; 79(2): 214 - 223.
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CirculationHome page
J. Rehman, D. Traktuev, J. Li, S. Merfeld-Clauss, C. J. Temm-Grove, J. E. Bovenkerk, C. L. Pell, B. H. Johnstone, R. V. Considine, and K. L. March
Secretion of Angiogenic and Antiapoptotic Factors by Human Adipose Stromal Cells
Circulation, March 16, 2004; 109(10): 1292 - 1298.
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J ANIM SCIHome page
J. Novakofski
Adipogenesis: Usefulness of in vitro and in vivo experimental models
J Anim Sci, March 1, 2004; 82(3): 905 - 915.
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BloodHome page
O. K. Lee, T. K. Kuo, W.-M. Chen, K.-D. Lee, S.-L. Hsieh, and T.-H. Chen
Isolation of multipotent mesenchymal stem cells from umbilical cord blood
Blood, March 1, 2004; 103(5): 1669 - 1675.
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CirculationHome page
V. Planat-Benard, J.-S. Silvestre, B. Cousin, M. Andre, M. Nibbelink, R. Tamarat, M. Clergue, C. Manneville, C. Saillan-Barreau, M. Duriez, et al.
Plasticity of Human Adipose Lineage Cells Toward Endothelial Cells: Physiological and Therapeutic Perspectives
Circulation, February 10, 2004; 109(5): 656 - 663.
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Circ. Res.Home page
V. Planat-Benard, C. Menard, M. Andre, M. Puceat, A. Perez, J.-M. Garcia-Verdugo, L. Penicaud, and L. Casteilla
Spontaneous Cardiomyocyte Differentiation From Adipose Tissue Stroma Cells
Circ. Res., February 6, 2004; 94(2): 223 - 229.
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CirculationHome page
T. Nakamura and M. D. Schneider
The Way to a Human's Heart Is Through the Stomach: Visceral Endoderm-Like Cells Drive Human Embryonic Stem Cells to a Cardiac Fate
Circulation, June 3, 2003; 107(21): 2638 - 2639.
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