Exaggerated replication in culture of adipocyte precursors from massively obese persons

Roncari, Daniel A. K.; Lau, David C.W.; Kindler, Sara

doi:10.1016/0026-0495(81)90174-8

Cited by 99 publications

(63 citation statements)

References 5 publications

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“…Finally, proliferation capacity and functionality of ASCs is strongly influenced by the BMI of the patients, showing increased activity in some massively obese patients compared to lean controls (22). Therefore, obese patients (BMI≥30 kg/m 2 ) were excluded from our study and the BMI of our participants was 28 kg/m 2 .…”

Section: Discussionmentioning

confidence: 99%

Comparison of the Viability and Yield of Adipose-Derived Stem Cells (ASCs) from Different Donor Areas

Tsekouras

Mantas

Tsilimigras

et al. 2017

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Over the last few years, autologous fat grafting has been at the forefront of aesthetic plastic surgery clinical practice, since it provides exceptional results for the treatment of soft-tissue contour deformities (1, 2). Similar to bone marrow, the adipose tissue is derived from the embryonic mesenchyme and contains a supportive stromal vascular fraction (SVF) that can be easily isolated (3). Typically, SVF from adipose tissue contains different types of cells, including endothelial cells, smooth muscle cells, pericytes, leukocytes and pre-adipocytes, otherwise named as adipose-derived stem cells (ASCs) (4).The potential of ASCs to differentiate into diverse cell types both in vitro and in vivo, offers outstanding opportunities for their clinical application as therapeutic agents (5). In particular, preclinical studies have revealed their capacity to differentiate toward the osteogenic, adipogenic, myogenic, and chondrogenic lineages (6, 7). Nevertheless, adipose tissue displays a significant heterogeneity in terms of stem cell yield, proliferation, and differentiation capacity not only among individuals, but even when comparing different fat depots within one individual (8). 1229This article is freely accessible online.Correspondence to: Diamantis I. Tsilimigras, MD,

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Section: Discussionmentioning

confidence: 99%

Comparison of the Viability and Yield of Adipose-Derived Stem Cells (ASCs) from Different Donor Areas

Tsekouras

Mantas

Tsilimigras

et al. 2017

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“…Similar differences occur with aging, which is associated with decreased proliferation ( 35,37,38 ) and adipogenesis (41)(42)(43) of SVCs; the latter perhaps accounts for observed increases in preadipocyte number with age ( 44 ). In contrast, SVC proliferation is enhanced in massively obese humans ( 45 ), although obesity may only be associated with impaired SVC adipogenesis in older individuals ( 32,46 ). Ultimately, such studies of SVC adipogenesis have highlighted how preadipocyte function might impact whole WAT biology in normal and disease states.…”

Section: Expanding Knowledge Of Adipogenesismentioning

confidence: 91%

Adipose tissue stem cells meet preadipocyte commitment: going back to the future

Cawthorn

Scheller

MacDougald

2012

Journal of Lipid Research

373

323

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with ill health. Such stigmatization distracts from a fascinating aspect of WAT biology: its enormous plasticity as an organ. Indeed, WAT is capable of massive expansion and contraction in response to chronic alterations in energy balance, accounting for as little as 5% body mass in extremely lean athletes ( 1 ) or as much as 60% body mass in morbidly obese individuals ( 2 ). Moreover in rodents, rabbits, and humans, WAT can regenerate following lipectomy ( 3-6 ). This striking degree of plasticity is unique among organs in adults. On a cellular level, WAT expansion is driven by both hypertrophy and hyperplasia of adipocytes ( 7-13 ). Even in nonexpanding WAT, adipocytes renew frequently to compensate for adipocyte death, with approximately 10% of adipocytes renewed annually ( 14,15 ). These data, which indicate that committed adipocyte progenitors (preadipocytes) exist within WAT, are the product of decades of research motivated largely by our desire to understand adipose tissue in the context of obesity and related diseases. Preadipocytes exist in adipose tissueThough the notion of obesity as a disease has existed since at least the time of Hippocrates ( 16 ), investigation into the origins of the adipocyte and the individual contributions of adipocyte hypertrophy and hyperplasia to adipose bulk began in earnest only after the appearance of the stem cell concept, as related to blood cells, in the early 1900s ( 17 ). In the 1940s, histologic observations of the appearance of adipocytes in chambers implanted in the ears of live rabbits suggested that de novo fat formation was Abstract White adipose tissue (WAT) is perhaps the most plastic organ in the body, capable of regeneration following surgical removal and massive expansion or contraction in response to altered energy balance. Research conducted for over 70 years has investigated adipose tissue plasticity on a cellular level, spurred on by the increasing burden that obesity and associated diseases are placing on public health globally. This work has identifi ed committed preadipocytes in the stromal vascular fraction of adipose tissue and led to our current understanding that adipogenesis is important not only for WAT expansion, but also for maintenance of adipocyte numbers under normal metabolic states. At the turn of the millenium, studies investigating preadipocyte differentiation collided with developments in stem cell research, leading to the discovery of multipotent stem cells within WAT. Such adipose tissue-derived stem cells (ASCs) are capable of differentiating into numerous cell types of both mesodermal and nonmesodermal origin, leading to their extensive investigation from a therapeutic and tissue engineering perspective. However, the insights gained through studying ASCs have also contributed to more-recent progress in attempts to better characterize committed preadipocytes in adipose tissue. Thus, ASC research has gone back to its roots, thereby expanding our knowledge of preadipocyte commitment and adipose tissue biology. -Cawthorn, W. P., E. ...

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“…As previously mentioned, unlike SV40 T-Ag, HPV-E7 does not interact with the CBP/p300 transcriptional complex, 12 which has been recently described to be necessary for the induction of both PPARg and C/EBPa. Owing to a higher replication rate of preadipocytes derived from massively obese subjects, 22 the use of adipocyte precursors from subcutaneous abdominal adipose tissue of a subject with a BMI of 54 kg/m 2 could have facilitated the immortalization process. Nevertheless, our immortalization strategy does not appear to be specific of fat depots, since we have recently obtained a preadipose cell line derived from omental adipose tissue of the same subject.…”

Section: Discussionmentioning

confidence: 99%

Reconstitution of telomerase activity combined with HPV-E7 expression allow human preadipocytes to preserve their differentiation capacity after immortalization

et al. 2003

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Overexpression of SV40 T-antigen (SV40 T-Ag) has been widely used to overcome replicative senescence of human primary cells and to promote cell immortalization. However, in the case of certain cell types, such as preadipocytes, the differentiation process of immortalized cells is blocked by SV40 T-Ag expression. In this study, human telomerase reverse transcriptase (hTERT) and papillomavirus E7 oncoprotein (HPV-E7) genes were coexpressed in human preadipocytes to test whether this combination could maintain cell differentiation capacity after immortalization. We demonstrated that the HPV-E7/hTERT expressing preadipocytes displayed an indefinite life span. Interestingly, immortalized cells were diploid and presented no chromosomic alterations. These immortalized cells were able to accumulate and hydrolyze intracellular triglycerides and to express adipocyte markers. These data demonstrate, for the first time, that coexpression of hTERT and HPV-E7 in human preadipocytes allows cells not only to display an indefinite life span but also to retain their capacity to differentiate.

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Exaggerated replication in culture of adipocyte precursors from massively obese persons

Cited by 99 publications

References 5 publications

Comparison of the Viability and Yield of Adipose-Derived Stem Cells (ASCs) from Different Donor Areas

Comparison of the Viability and Yield of Adipose-Derived Stem Cells (ASCs) from Different Donor Areas

Adipose tissue stem cells meet preadipocyte commitment: going back to the future

Reconstitution of telomerase activity combined with HPV-E7 expression allow human preadipocytes to preserve their differentiation capacity after immortalization

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