Rapamycin Suppresses the Expansion and Differentiation of Porcine Neonatal Pancreas Cell Clusters

Sun, Chenglin; Ham, Dong-Sik; Park, Heon‐Seok; Kim, Jiwon; Cho, Jae‐Hyoung; Song, Ki‐Ho; Son, Ho‐Young; Yoon, Kun‐Ho

doi:10.1097/tp.0b013e3181eceaaf

Cited by 7 publications

(6 citation statements)

References 39 publications

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“…Rapamycin is also known to inhibit adipogenesis of preadipocytes [41]. For many cell types, including our findings in this present study, rapamycin slows down cell proliferation [31,32,[42][43][44][45], as it decreases p-P70S6K (Fig. 6B).…”

Section: Discussionsupporting

confidence: 63%

“…Western blot analysis of signaling events in DPSCs after treatment with SC1 or rapamycin (Rapa). Cells were treated with 300 nM SC1 (A) or 900 nM Rapa (B) for 5 days and subjected to protein extraction for detection of signaling factors RAS GAP, phosphorylated (p)-ERK1(44)/2 (42), and p-P70S6K shown in (A) or p-mTOR and p-p70S6K in (B). GAPDH: glyceraldehyde 3-phosphate dehydrogenase, CTRL: control nontreated.…”

Section: Figmentioning

confidence: 99%

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Small Molecules Affect Human Dental Pulp Stem Cell Properties Via Multiple Signaling Pathways

Al-Habib

Huang

2013

Stem Cells and Development

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One fundamental issue regarding stem cells for regenerative medicine is the maintenance of stem cell stemness. The purpose of the study was to test whether small molecules can enhance stem cell properties of mesenchymal stem cells (MSCs) derived from human dental pulp (hDPSCs), which have potential for multiple clinical applications. We identified the effects of small molecules (Pluripotin (SC1), 6-bromoindirubin-3-oxime and rapamycin) on the maintenance of hDPSC properties in vitro and the mechanisms involved in exerting the effects. Primary cultures of hDPSCs were exposed to optimal concentrations of these small molecules. Treated hDPSCs were analyzed for their proliferation, the expression levels of pluripotent and MSC markers, differentiation capacities, and intracellular signaling activations. We found that small molecule treatments decreased cell proliferation and increased the expression of STRO-1, NANOG, OCT4, and SOX2, while diminishing cell differentiation into odonto/osteogenic, adipogenic, and neurogenic lineages in vitro. These effects involved Ras-GAP-, ERK1/2-, and mTOR-signaling pathways, which may preserve the cell self-renewal capacity, while suppressing differentiation. We conclude that small molecules appear to enhance the immature state of hDPSCs in culture, which may be used as a strategy for adult stem cell maintenance and extend their capacity for regenerative applications.

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Section: Discussionsupporting

confidence: 63%

Section: Figmentioning

confidence: 99%

Small Molecules Affect Human Dental Pulp Stem Cell Properties Via Multiple Signaling Pathways

Al-Habib

Huang

2013

Stem Cells and Development

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“…In contrast, the islets were formed when NPCCs were separated and immediately transplanted without further in vitro manipulation as shown in Fig. 1 and published by others [23-25]. These discrepancies might be due to the loss of extracellular matrix or other factors which are required for islet structure formation, during the NPCCs dispersion into single cells.…”

Section: Discussionmentioning

confidence: 76%

Repeated Gene Transfection Impairs the Engraftment of Transplanted Porcine Neonatal Pancreatic Cells

et al. 2011

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BackgroundPreviously, we reported that neonatal porcine pancreatic cells transfected with hepatocyte growth factor (HGF) gene in an Epstein-Barr virus (EBV)-based plasmid (pEBVHGF) showed improved proliferation and differentiation compared to those of the control. In this study, we examined if pancreatic cells transfected repeatedly with pEBVHGF can be successfully grafted to control blood glucose in a diabetes mouse model.MethodsNeonatal porcine pancreatic cells were cultured as a monolayer and were transfected with pEBVHGF every other day for a total of three transfections. The transfected pancreatic cells were re-aggregated and transplanted into kidney capsules of diabetic nude mice or normal nude mice. Blood glucose level and body weight were measured every other day after transplantation. The engraftment of the transplanted cells and differentiation into beta cells were assessed using immunohistochemistry.ResultsRe-aggregation of the pancreatic cells before transplantation improved engraftment of the cells and facilitated neovascularization of the graft. Right before transplantation, pancreatic cells that were transfected with pEBVHGF and then re-aggregated showed ductal cell marker expression. However, ductal cells disappeared and the cells underwent fibrosis in a diabetes mouse model two to five weeks after transplantation; these mice also did not show controlled blood glucose levels. Furthermore, pancreatic cells transplanted into nude mice with normal blood glucose showed poor graft survival regardless of the type of transfected plasmid (pCEP4, pHGF, or pEBVHGF).ConclusionFor clinical application of transfected neonatal porcine pancreatic cells, further studies are required to develop methods of overcoming the damage for the cells caused by repeated transfection and to re-aggregate them into islet-like structures.

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“…We used monolayer-cultured cells for the experiments because reaggregation process also influences a lot on the cell survival. Previously, we already used dispersed NPCCs for the treatment and in vitro analysis (30). Also, many other researcher used monolayer NPCCs for insulin secretion (12,31,32).…”

Section: Discussionmentioning

confidence: 99%

Targeting PGC-1α to Overcome the Harmful Effects of Glucocorticoids in Porcine Neonatal Pancreas Cell Clusters

Kim

Park²,

You³

et al. 2014

Transplantation

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Rapamycin Suppresses the Expansion and Differentiation of Porcine Neonatal Pancreas Cell Clusters

Abstract: Here, we demonstrate that rapamycin treatment suppresses the expansion and differentiation of porcine NPCCs, and the alteration of Foxo1 and insulin-like growth factor-II gene expression might be the crucial factors.

Cited by 7 publications

References 39 publications

Small Molecules Affect Human Dental Pulp Stem Cell Properties Via Multiple Signaling Pathways

Small Molecules Affect Human Dental Pulp Stem Cell Properties Via Multiple Signaling Pathways

Repeated Gene Transfection Impairs the Engraftment of Transplanted Porcine Neonatal Pancreatic Cells

Targeting PGC-1α to Overcome the Harmful Effects of Glucocorticoids in Porcine Neonatal Pancreas Cell Clusters

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