Pleiotrophin Enhances Clonal Growth and Long-Term Expansion of Human Embryonic Stem Cells

Soh, Boon Seng; Song, Chun Meng; Vallier, Ludovic; Пин, Ли; Choong, Cleo; Yeo, Boon Huat; Lim, Elaine; Pedersen, Roger A.; Yang, Henry; Rao, Mahendra S.; Lim, Bing

doi:10.1634/stemcells.2007-0372

Cited by 55 publications

(42 citation statements)

References 28 publications

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“…PTN and MK are 50 percent homologous in amino acid sequence and share the same receptors. In a recent study, PTN has been reported to work as a self-renewal enhancer in hESCs [23] . In our study, we found that MK has similar effects as PTN in the hESC culture system.…”

Section: Discussionmentioning

confidence: 97%

“…It is 50% homologous to PTN at the amino acid level and shares the genomic organization and protein structure of PTN. PTN has been shown to be expressed in hESCs and to use PTPζ to activate PI3K/AKT to enhance the long-term expansion of hESCs [23] . To examine the effects of MK signaling on hESCs, the expression of MK on hESCs, HUES3 and ZJUhES-1, was tested.…”

Section: Mk-ptpζ Pathwaymentioning

confidence: 99%

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Promotion of self-renewal of embryonic stem cells by midkine

Yao

Tan

et al. 2010

Acta Pharmacol Sin

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Aim: To characterize the expression and function of midkine (MK) in an in vitro embryonic stem cell (ESC) culture system. Methods: To investigate the potential roles of MK, the expression of MK in ESCs was evaluated by RT-PCR and immunocytochemistry. The effects of MK on the self-renewal of ESCs were measured using alkaline phosphatase assays, immunocytochemistry, RT-PCR and colony-forming assays. The mechanism of the growth-promoting effect of MK in mESCs was assessed by cell cycle analysis and Western blot analysis. Results: MK is expressed in mouse embryonic stem cells (mESCs), human embryonic stem cells (hESCs) and mouse embryonic fibroblasts (MEFs). MK promotes proliferation and self-renewal of mESCs both in feeder and feeder free culture systems. It also promotes self-renewal and proliferation of hESCs. Further study showed that MK promotes the growth of mESCs by inhibiting apoptosis while accelerating the progression toward the S phase, and enhances mESC self-renewal through PI3K/Akt signaling pathway. Conclusion: MK plays profound roles in ESCs. MK/PTPζ signaling pathway is a novel pathway in the signal network maintaining pluripotency of ESCs. The results extend our knowledge on pluripotency control of ESCs and the relationship between ESCs and cancers.

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Section: Discussionmentioning

confidence: 97%

Section: Mk-ptpζ Pathwaymentioning

confidence: 99%

Promotion of self-renewal of embryonic stem cells by midkine

Yao

Tan

et al. 2010

Acta Pharmacol Sin

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“…46 PTN was shown to play an important role in survival and large-scale propagation of human embryonic stem cells and down-regulation of this factor fits with the observed decline of proliferation capacity of senescent MSC. 47 It has been demonstrated that replicative senescence impairs the differentiation potential of MSC. Surprisingly, this study showed obvious similarities regarding senescence-associated gene expression changes irrespectively of whether MSC were propagated with fetal animal serum or adult human serum substitution.…”

mentioning

confidence: 99%

Replicative senescence-associated gene expression changes in mesenchymal stromal cells are similar under different culture conditions

Schallmoser¹,

Bartmann²,

Rohde³

et al. 2010

Haematologica

108

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BackgroundResearch on mesenchymal stromal cells has created high expectations for a variety of therapeutic applications. Extensive propagation to yield enough mesenchymal stromal cells for therapy may result in replicative senescence and thus hamper long-term functionality in vivo. Highly variable proliferation rates of mesenchymal stromal cells in the course of long-term expansions under varying culture conditions may already indicate different propensity for cellular senescence. We hypothesized that senescence-associated regulated genes differ in mesenchymal stromal cells propagated under different culture conditions. Design and MethodsHuman bone marrow-derived mesenchymal stromal cells were cultured either by serial passaging or by a two-step protocol in three different growth conditions. Culture media were supplemented with either fetal bovine serum in varying concentrations or pooled human platelet lysate. ResultsAll mesenchymal stromal cell preparations revealed significant gene expression changes upon long-term culture. Especially genes involved in cell differentiation, apoptosis and cell death were up-regulated, whereas genes involved in mitosis and proliferation were down-regulated. Furthermore, overlapping senescence-associated gene expression changes were found in all mesenchymal stromal cell preparations. ConclusionsLong-term cell growth induced similar gene expression changes in mesenchymal stromal cells independently of isolation and expansion conditions. In advance of therapeutic application, this panel of genes might offer a feasible approach to assessing mesenchymal stromal cell quality with regard to the state of replicative senescence.

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“…Primary MEFs are not homogeneous, as they contain several types of cells other than fibroblasts [13]. To maintain ESC proliferation and pluripotency, MEFs produce various proteins, including transforming growth factor beta 1 (TGF-β1), activin A, bone morphogenetic protein (BMP)-4 [14], and pleiotrophin (heparin-binding growth factor) [15]. When used as in feeder cell layers, MEFs are proliferation-inactivated by chemical (mitomycin C) treatment or gamma irradiation prior to seeding of ESCs/iPSCs.…”

Section: Mouse-derived Feeder Cellsmentioning

confidence: 99%

Feeder Cell Sources and Feeder-Free Methods for Human iPS Cell Culture

Kamano

Wang

et al. 2015

Interface Oral Health Science 2014

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Induced pluripotent stem cells (iPSCs) hold great promise for regenerative medicine and disease modeling. The original methods to grow human iPSCs utilized methods developed for human embryonic cells (ESCs), in which mitotically inactivated mouse-derived fibroblasts are mainly used as a "feeder" cell layer to maintain the undifferentiated status of pluripotent stem cells. However, these methods still require further consideration to facilitate cell expansion and to maintain the undifferentiated state of human iPSCs and/or ESCs for a longer period of time. In addition, the use of animal-derived feeders should be avoided for eventual clinical application of iPSC therapies. Therefore, human-derived feeder culture systems or feeder-free culture systems are currently being developed to prevent exposure to animal pathogens. In this review, existing mouse and human feeder culture systems for human ESCs and iPSCs are first introduced, and then previously reported feeder-free culture methods using extracellular matrixassociated products or synthetic biomaterials are outlined to discuss an appropriate culture system for clinical application of iPSCs.

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Pleiotrophin Enhances Clonal Growth and Long-Term Expansion of Human Embryonic Stem Cells

Cited by 55 publications

References 28 publications

Promotion of self-renewal of embryonic stem cells by midkine

Promotion of self-renewal of embryonic stem cells by midkine

Replicative senescence-associated gene expression changes in mesenchymal stromal cells are similar under different culture conditions

Feeder Cell Sources and Feeder-Free Methods for Human iPS Cell Culture

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