Increased caveolin-1, a cause for the declined adipogenic potential of senescent human mesenchymal stem cells

Park, Jeong‐Soo; Kim, Hee-Young; Kim, Hyang-Won; Chae, Gi-Nam; Oh, Hyung-Tae; Park, Jin‐Young; Shim, Hosup; Seo, Min‐Ju; Shin, Eun‐Young; Park, Sang Chul; Kwak, Sahng‐June

doi:10.1016/j.mad.2004.11.014

Cited by 94 publications

(67 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Caveolin-1 is a structural component of caveolae (vesicular invaginations of the plasma membrane) that participates in trafficking events as part of signal transduction. Furthermore, expression of caveolin-1 by MSC inhibits differentiation, and MSC from the marrow of older people express caveolin [64]. These observations offer an intriguing link between SIPS and ageing.…”

Section: Senescencementioning

confidence: 87%

Morphology, mechanisms and pathology of musculoskeletal ageing

Freemont

Hoyland

2007

The Journal of Pathology

107

View full text Add to dashboard Cite

In general terms, the recognized alterations in circulating humoral factors (hormones, cytokines, growth factors) that occur in ageing, coupled with innate cellular senescence exaggerated by the slow turnover of many connective tissue cell populations and the ageassociated alterations in matrix molecule cross-linking, predispose the elderly to altered connective tissue biology. These changes can be profound, leading to poor mobility, altered ability to withstand cold, weakness and an increased risk of falls, fractures and age-associated 'degenerative' diseases, such as osteoarthritis and osteoporosis. As understanding of the causes of altered connective tissue function with age increases, it is becoming clearer that many of the predisposing factors (growth hormone, cytokines, load/life style) are potential targets for improving quality of life in the elderly.

show abstract

Section: Senescencementioning

confidence: 87%

Morphology, mechanisms and pathology of musculoskeletal ageing

Freemont

Hoyland

2007

The Journal of Pathology

107

View full text Add to dashboard Cite

show abstract

“…In other studies, MSCs isolated from adult BM cultured in similar conditions were reportedly able to maintain both their phenotype and ability to differentiate throughout multiple passages. 15,22,24 However, similar studies have reported changes in MSC morphology and phenotype with repeated passages in vitro [28][29][30] and have also emphasized the loss of adipogenic potential with higher passage numbers. One study of MSCs isolated from human BM summarized that most MSCs undergoing in vitro expansion lose telomeres with each cell division until reaching a threshold where division ceases and cells assume a senescent phenotype.…”

Section: Discussionmentioning

confidence: 99%

“…30 Another in vitro study correlated changes in morphology, progressive loss of adipogenic potential and senescent phenotype with an increase in caveolin-1 expression. 29 In addition, the authors of the latter study concluded that the capacity of adult stem cells could be reflective of donor age, tissue source and biological aging. 29 Therefore, the phenotypic changes we observed at higher passages and the loss of adipogenic potential are not unique features that can be attributed to pancreatic MSCs or the culture conditions used in our study.…”

Section: Discussionmentioning

confidence: 99%

“…29 In addition, the authors of the latter study concluded that the capacity of adult stem cells could be reflective of donor age, tissue source and biological aging. 29 Therefore, the phenotypic changes we observed at higher passages and the loss of adipogenic potential are not unique features that can be attributed to pancreatic MSCs or the culture conditions used in our study. Rather, this common characteristic of loss of potential serves to emphasize the limitations faced when expanding adult stem cells.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Expansion of mesenchymal stem cells from human pancreatic ductal epithelium

Seeberger

Dufour

Shapiro

et al. 2006

Laboratory Investigation

152

142

View full text Add to dashboard Cite

Fibroblast-like cells emerging from cultured human pancreatic endocrine and exocrine tissue have been reported. Although a thorough phenotypic characterization of these cells has not yet been carried out, these cells have been hypothesized to be contaminating fibroblasts, mesenchyme and/or possibly beta-cell progenitors. In this study, we expanded fibroblast-like cells from adult human exocrine pancreas following islet isolation and characterized these cells as mesenchymal stem cells (MSCs) based on their cell surface antigen expression and ability to differentiate into mesoderm. Analysis by flow cytometry demonstrated that pancreatic MSCs express cell surface antigens used to define MSCs isolated from bone marrow such as CD13, CD29, CD44, CD49b, CD54, CD90 and CD105. In addition, utilizing protocols used to differentiate MSCs isolated from other somatic tissues, we successfully differentiated pancreatic MSCs into: (1) osteocytes that stained positive for alkaline phosphatase, collagen, mineralization (calcification) and expressed osteocalcin, (2) adipocytes that contained lipid inclusions and expressed fatty acid binding protein 4 and (3) chondrocytes that expressed aggrecan. We also demonstrated that pancreatic MSCs are multipotent and capable of deriving cells of endodermal origin. Pancreatic MSCs were differentiated into hepatocytes that stained positive for human serum albumin and expressed endoderm and liver-specific genes such as GATA 4 and tyrosine aminotransferase. In addition, preliminary protocols used to differentiate these cells into insulin-producing cells resulted in the expression of genes necessary for islet and beta-cell development such as Pax4 and neurogenin 3. Therefore, multipotent MSCs residing within the adult exocrine pancreas could represent a progenitor cell, which when further manipulated could result in the production of functional islet beta-cells.

show abstract

“…Three different cases were considered: young (up to 20 years old), adult (about 55 years old) and elder (more than 70 years old) patients. Based on the histological analyses conducted by Chen et al, (Chen et al, 2005), Baxter et al, (Baxter et al, 2004), Mendes et al (Mendes et al, 2002), and Park et al (Park et al, 2005), the diffusion coefficient D was hypothesized to be a function of the patient's age. Let t elder , t adult and t young be the time periods required by MSCs for recovering completely the bone callus domain respectively for the elder, adult and young patients.…”

Section: Determination Of the Optimal Duration Of The Latency Period mentioning

confidence: 99%