Adipose-derived stromal cells—their utility and potential in bone formation

Halvorsen, Yuan-Di C.; Wilkison, William O.; Gimble, J. M.

doi:10.1038/sj.ijo.0801503

Cited by 193 publications

(134 citation statements)

References 7 publications

(8 reference statements)

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“…Recent studies have confirmed the existence of an abundant and easily accessible source of multipotent stem cells in subcutaneous or intraarticular adipose tissue (13)(14)(15)(16)(17)(18)(19)(20)(21). Cells obtained from adipose tissue have been termed processed lipoaspirate cells, adiposederived adult stromal/stem cells (ADAS cells), or simply adipose-derived stem cells.…”

mentioning

confidence: 99%

Potent induction of chondrocytic differentiation of human adipose‐derived adult stem cells by bone morphogenetic protein 6

Estes

Guilak

2006

Arthritis & Rheumatism

269

212

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Objective. Recent studies have identified an abundant source of multipotent progenitor cells in subcutaneous human adipose tissue, termed human adiposederived adult stem cells (ADAS cells). In response to specific media formulations, including transforming growth factor ␤1 (TGF␤1), these cells exhibit significant ability to differentiate into a chondrocyte-like phenotype, expressing cartilage-specific genes and proteins such as aggrecan and type II collagen. However, the influence of other growth factors on the chondrogenic differentiation of ADAS cells is not fully understood. This study was undertaken to investigate the effects of TGF␤1, TGF␤3, insulin-like growth factor 1, bone morphogenetic protein 6 (BMP-6), and dexamethasone, in various combinations, on the chondrogenic potential of ADAS cells in alginate beads.Methods. The chondrogenic response of alginateencapsulated ADAS cells was measured by quantitative polymerase chain reaction, 3 H-proline and 35 S-sulfate incorporation, and immunolabeling for specific extracellular matrix components.Results. Significant differences in chondrogenesis were observed under the different culture conditions for all outcomes measured. Most notably, BMP-6 upregulated AGC1 and COL2A1 expression by an average of 205-fold and 38-fold, respectively, over day-0 controls, while down-regulating COL10A1 expression by ϳ2-fold.Conclusion. These findings suggest that BMP-6 is a potent inducer of chondrogenesis in ADAS cells, in contrast to mesenchymal stem cells, which exhibit increased expression of type X collagen and a hypertrophic phenotype in response to BMP-6. Combinations of growth factors containing BMP-6 may provide a novel means of regulating the differentiation of ADAS cells for applications in the tissue-engineered repair or regeneration of articular cartilage.

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confidence: 99%

Potent induction of chondrocytic differentiation of human adipose‐derived adult stem cells by bone morphogenetic protein 6

Estes

Guilak

2006

Arthritis & Rheumatism

269

212

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“…Under controlled in vitro conditions, ASCs can be induced to synthesize various tissue-specific matrix proteins of both mesodermal and ectodermal lineages (Awad et al 2004;De Ugarte et al 2003;Dragoo et al 2003;Erickson et al 2002;Estes et al 2006a;Estes et al 2006b;Gimble and Guilak 2003b;Guilak et al 2006;Halvorsen et al 2000;Huang et al 2004;Mizuno et al 2002;Safford et al 2002;Wall et al 2007;Wang et al 2005;Wickham et al 2003). The ability to differentiate the ASCs along various mesodermal lineages persists even after extended passaging (Estes et al 2006b;Wall et al 2007;Zuk et al 2001).…”

Section: Introductionmentioning

confidence: 99%

Monolayer cell expansion conditions affect the chondrogenic potential of adipose‐derived stem cells

Estes

Diekman

Guilak

2008

Biotech & Bioengineering

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Adipose-derived stem cells (ASCs) are an abundant, readily available population of multipotent progenitor cells that reside in adipose tissue. Isolated ASCs are typically expanded in monolayer on standard tissue culture plastic with a basal medium containing 10% fetal bovine serum. However, recent data suggests that altering the monolayer expansion conditions by using suspension culture plastic, adding growth factors to the medium, or adjusting the seeding density may affect the self-renewal rate, multipotency, and lineage-specific differentiation potential of the ASCs. We hypothesized that variation in any of these expansion conditions would influence the chondrogenic potential of ASCs. ASCs were isolated from human liposuction waste tissue and expanded through two passages with different tissue culture plastic, feed medium, and cell seeding densities. Once expanded, the cells were cast in an agarose gel and subjected to identical chondrogenic culture conditions for 7 days, at which point cell viability, radiolabel incorporation, and gene expression were measured. High rates of matrix synthesis upon chondrogenic induction were mostly associated with smaller cells, as indicated by cell width and area on tissue culture plastic, and it appears that expansion in a growth factor supplemented medium is important in maintaining this morphology. All end-point measures were highly dependent on the specific monolayer culture conditions. These results support the hypothesis that monolayer culture conditions may "prime" the cells or predispose them towards a specific phenotype and thus underscore the importance of early culture conditions in determining the growth and differentiation potential of ASCs.

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“…[3][4][5][6] As Green et al 7 reported that adipose tissue contains 'Preadipocytes' in 1974, a number of investigations have been reported regarding adipose tissue-derived stem/progenitor cells, so-called 'adipose-derived stromal cells (ADSCs). [3][4][5]8 Other adipogenic cell populations 3,9,10 have also been established with the multipotency of differentiation into not only mesenchymal lineage cells such as osteoblasts, 11,12 chondrocytes, 11,13,14 myocytes, 12 cardiomyocytes, 15 fibroblasts 3 and adipocytes 12 but also vascular lineage cells 15,16 such as endothelial, smooth muscle and circulating blood cells in stromal vascular fraction (SVF) isolated from adipose tissue. Among the variety of ADSCs, human multipotent adipose-derived stem (hMADS) cells 6 isolated from young donors show fast adherent cell characteristics in culture and have more extensive expansion capacity ex vivo over 200 passages.…”

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confidence: 99%

Local transplantation of human multipotent adipose-derived stem cells accelerates fracture healing via enhanced osteogenesis and angiogenesis

Shoji

Masaaki

Mifune

et al. 2010

Laboratory Investigation

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Adipose tissue is one of the promising sources of multipotent stem cells in human. Human multipotent adipose-derived stem (hMADS) cells have recently been isolated and showed differentiation potential into multiple mesenchymal lineages in vitro and in vivo. On the basis of these evidences, we examined the therapeutic efficacy of hMADS cells for fracture healing in an immunodeficient rat femur non-union fracture model. Local transplantation of hMADS cells radiographically and histologically promoted fracture healing with significant improvement of biomechanical function at the fracture sites compared with local transplantation of human fibroblasts (hFB) or PBS administration. Histological capillary density and physiological blood flow by laser Doppler perfusion imaging were significantly greater in hMADS group than hFB and PBS groups. Expressions of intrinsic (rat) bone morphogenetic protein-2 (BMP-2), vascular endothelial growth factor (VEGF) and angiopoietin-1 in peri-fracture tissue were upregulated in hMADS group than other groups. In addition, presence of BMP-2 or VEGF activated the proliferation and migration of hMADS cells in vitro. These results indicate that hMADS cells stimulate the interaction between the transplanted cells and the resident cells stronger than other cells, and they promote fracture healing more effectively. Furthermore, immunohistochemistry for human-specific antibodies revealed direct differentiation of hMADS cells into osteoblasts or endothelial cells in newly formed callus or vasculature, respectively. RT-PCR for human-specific primers for osteogenic/endothelial markers also disclosed osteogenic and vasculogenic plasticity of the transplanted hMADS cells at the early stage of fracture healing. The present results suggest that transplantation of hMADS cells may become a useful strategy for cell-based bone regeneration in the future clinical setting.

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Adipose-derived stromal cells—their utility and potential in bone formation

Cited by 193 publications

References 7 publications

Potent induction of chondrocytic differentiation of human adipose‐derived adult stem cells by bone morphogenetic protein 6

Potent induction of chondrocytic differentiation of human adipose‐derived adult stem cells by bone morphogenetic protein 6

Monolayer cell expansion conditions affect the chondrogenic potential of adipose‐derived stem cells

Local transplantation of human multipotent adipose-derived stem cells accelerates fracture healing via enhanced osteogenesis and angiogenesis

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