Human Adipose Tissue Is a Source of Multipotent Stem Cells

Molecular Biology of the Cell - Tập 13 Số 12 - Trang 4279-4295 - 2002
Patricia A. Zuk1, Min Zhu2, Peter Ashjian2, Daniel A. De Ugarte2, Jerry I. Huang2, Hiroshi Mizuno2, Zeni Alfonso3, John K. Fraser3, Prosper Benhaim2, Marc H. Hedrick2
1Department of Surgery and Orthopedics, Regenerative Bioengineering and Repair Laboratory, UCLA School of Medicine, Los Angeles, California 90095, USA. [email protected]
2Departments of Surgery and Orthopedics, Regenerative Bioengineering and Repair Laboratory, UCLA School of Medicine, Los Angeles, California 90095; and
3Department of Medicine and the Jonsson Comprehensive Cancer Center, Division of Hematology and Oncology, UCLA School of Medicine, Los Angeles, California 90095

Tóm tắt

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 whether 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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Tài liệu tham khảo

Ailhaud G., 1992, Annu. Rev. Nutr., 12, 207, 10.1146/annurev.nu.12.070192.001231

Atchley W.R., 1994, Proc. Natl. Acad. Sci. USA, 91, 11522, 10.1073/pnas.91.24.11522

Benayahu D., 1989, J. Cell Physiol., 140, 1, 10.1002/jcp.1041400102

Bennett J.H., 1991, J. Cell Sci., 99, 131, 10.1242/jcs.99.1.131

Benson M.D., 2000, J. Biol. Chem., 275, 13907, 10.1074/jbc.275.18.13907

Beresford J.N., 1986, Endocrinology, 119, 1776, 10.1210/endo-119-4-1776

Bernlohr D.A., 1985, Biochem. Biophys. Res. Commun., 132, 850, 10.1016/0006-291X(85)91209-4

Bjornson C.R.R., 1999, Science, 283, 534, 10.1126/science.283.5401.534

Breen E.C., 1994, J. Cell Biochem., 160, 323, 10.1002/jcp.1041600214

Bruder S.P., 1997, J. Cell Biochem., 64, 278, 10.1002/(SICI)1097-4644(199702)64:2<278::AID-JCB11>3.0.CO;2-F

Bruder S.P., 1998, J. Orthop. Res., 16, 155, 10.1002/jor.1100160202

Chen X., 1997, Biochim. Biophys. Acta, 1359, 136, 10.1016/S0167-4889(97)00083-9

Conget P.A., 1999, J. Cell Physiol., 181, 67, 10.1002/(SICI)1097-4652(199910)181:1<67::AID-JCP7>3.0.CO;2-C

Cooper M.S., 1999, J. Endocrinol., 163, 159, 10.1677/joe.0.1630159

Deng W., 2001, Biochem. Biophys. Res. Commun., 282, 148, 10.1006/bbrc.2001.4570

Dennis J.E., 2002, Cells Tissues Organs, 170, 73, 10.1159/000046182

Dennis J.E., 1999, J. Bone Miner. Res., 14, 700, 10.1359/jbmr.1999.14.5.700

Ducy P., 1997, Cell., 89, 747, 10.1016/S0092-8674(00)80257-3

Evans M., 1981, Nature, 292, 154, 10.1038/292154a0

Farndale R.W., 1986, Biochim. Biophys. Acta, 883, 173, 10.1016/0304-4165(86)90306-5

Ferrari G., 1998, Science, 279, 1528, 10.1126/science.279.5356.1528

Friedenstein A.J., 1990, Bone and Mineral Research, 7, 243, 10.1016/B978-0-444-81371-8.50012-1

Galli R., 2000, Nat. Neurosci., 3, 986, 10.1038/79924

Galotto M., 1994, J. Bone Miner. Res., 9, 1239, 10.1002/jbmr.5650090814

Green H., 1974, Cell, 3, 127, 10.1016/0092-8674(74)90116-0

Grigoradis A., 1988, J. Cell Biol., 106, 2139, 10.1083/jcb.106.6.2139

Gronthos S., 1994, Blood, 84, 4164, 10.1182/blood.V84.12.4164.bloodjournal84124164

Hall P.A., 1989, Development, 106, 619, 10.1242/dev.106.4.619

Hauner H., 1987, J. Clin. Endocrinol. Metabol., 64, 832, 10.1210/jcem-64-4-832

Haynesworth S.E., 1992, Bone, 13, 69, 10.1016/8756-3282(92)90363-2

Jabs E.W., 1993, Cell, 75, 443, 10.1016/0092-8674(93)90379-5

Jaiswal N., 1997, J. Cell. Biochem., 64, 295, 10.1002/(SICI)1097-4644(199702)64:2<295::AID-JCB12>3.0.CO;2-I

Johnson E.E., 1988, Clin. Orthop., 236, 249, 10.1097/00003086-198811000-00034

Johnstone B., 1998, Exp. Cell Res., 238, 265, 10.1006/excr.1997.3858

Jonasson L., 1984, Atherosclerosis, 51, 313, 10.1016/0021-9150(84)90179-5

Kuri-Harcuch W., 1978, Biol. Chem., 252, 2158, 10.1016/S0021-9258(18)71879-6

Lassar A., 1994, Curr. Opin. Cell Biol., 6, 432, 10.1016/0955-0674(94)90037-X

Leboy P.S., 1991, J. Cell Physiol., 146, 370, 10.1002/jcp.1041460306

Legasse E., 2000, Nutr. Med., 6, 1229

Lendahl U., 1990, Cell, 60, 585, 10.1016/0092-8674(90)90662-X

Lennon D.P., 1996, In Vitro Cell Dev. Biol., 32, 602, 10.1007/BF02724045

Levesque J.B., 2001, Blood., 98, 1289, 10.1182/blood.V98.5.1289

Lieberman J.R., 1998, J. Orthop. Res., 16, 330, 10.1002/jor.1100160309

Lucas P.A., 1992, In Vitro Cell Biol., 28, 154A, 10.1007/BF02631084

Majeska R.J., 1982, J. Biol. Chem., 257, 3362, 10.1016/S0021-9258(18)34781-1

Malaval L., 1994, J. Cell Physiol., 158, 555, 10.1002/jcp.1041580322

Mizuno H., 2001, Plastic Reconstr. Surg., 109, 199, 10.1097/00006534-200201000-00030

Mullen R.J., 1992, Development, 116, 210, 10.1242/dev.116.1.201

Muraglia A., 2000, J. Cell Sci., 113, 1161, 10.1242/jcs.113.7.1161

Newberry E.P., 1998, Biochemistry, 37, 16360, 10.1021/bi981878u

Ogeuch O., 2000, J. Clin. Endo. Meta., 85, 1997, 10.1210/jcem.85.5.6591

Osdoby P., 1979, Dev. Biol., 73, 84, 10.1016/0012-1606(79)90140-4

Owen T.A., 1990, J. Cell Physiol., 143, 420, 10.1002/jcp.1041430304

Pittenger M.F., 1999, Science, 284, 143, 10.1126/science.284.5411.143

Reddi A.H., 1982, Prog. Clin. Biol. Res., 110, 261

Rikard D.J., 1994, Dev. Biol., 161, 218, 10.1006/dbio.1994.1022

Ryoo H.M., 1997, Mol. Endocrinol., 11, 1681, 10.1210/mend.11.11.0011

Sanchez-Ramos J., 2000, Exp. Neurol., 164, 247, 10.1006/exnr.2000.7389

Satomura K., 2000, J. Cell Biochem., 78, 391, 10.1002/1097-4644(20000901)78:3<391::AID-JCB5>3.0.CO;2-E

Shamblott M.J., 1998, Proc. Natl. Acad. Sci. USA, 95, 13726, 10.1073/pnas.95.23.13726

Tachetti C., 1987, J. Cell Biol., 106, 999, 10.1083/jcb.105.2.999

Tanner J.W., 1992, Biochem. J., 182, 99, 10.1042/bj2820099

Toma J.G., 2001, Nat. Cell Biol., 3, 778, 10.1038/ncb0901-778

Totonoz P., 1994, Genes Dev., 8, 1224, 10.1101/gad.8.10.1224

Wakitani S., 1995, Muscle Nerve, 18, 1417, 10.1002/mus.880181212

Wang E.A., 1990, Proc. Natl. Acad. Sci. USA, 87, 2220, 10.1073/pnas.87.6.2220

Westin S., 1988, Nature, 395, 199, 10.1038/26040

Wise L.S., 1979, J. Biol. Chem., 254, 273, 10.1016/S0021-9258(17)37913-9

Woodbury D., 2000, J. Neurosci. Res., 61, 364, 10.1002/1097-4547(20000815)61:4<364::AID-JNR2>3.0.CO;2-C

Yoo J.U., 1998, J. Bone Joint Surg. Am., 80, 1745, 10.2106/00004623-199812000-00004

Young H.E., 1995, Dev. Dyn., 202, 137, 10.1002/aja.1002020205

Zuk P.A., 2001, Tissue Eng., 7, 211, 10.1089/107632701300062859