Embryonic stem cells: Meeting the needs for cell therapy

Mitjavila-Garcia, Maria Teresa; Simonin, C.; Peschanski, Marc

doi:10.1016/j.addr.2005.06.001

Cited by 22 publications

(21 citation statements)

References 61 publications

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“…Nowadays, several candidates of stem cells, including embryonic stem cells, BMMSCs and peripheral blood-derived stem cells have been commonly investigated for their feasibility and safety in the treatment of diabetes mellitus and its complications in both clinical observational studies and animal models (24). However, the application of these stem cells for diabetic patients is frequently hampered by many limitations, including ethical problems with using embryonic stem cells, difficulties in differentiation lineage restriction and identification as well as limitation of number and functional integrity in peripheral blood-revived stem cells and BMMSCs (25,26). The most important finding in the present study is that numerous CM-Dil-labeled ADMSCs were identified in renal parenchyma of diabetic rats at 12 weeks after induction of diabetes.…”

Section: Discussionmentioning

confidence: 99%

Autologous transplantation of adipose-derived mesenchymal stem cells ameliorates streptozotocin-induced diabetic nephropathy in rats by inhibiting oxidative stress, pro-inflammatory cytokines and the p38 MAPK signaling pathway

et al. 2012

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Abstract. Diabetic nephropathy is the leading cause of endstage renal disease. The aim of this study was to investigate the renoprotective effects of autologous transplantation of adiposederived mesenchymal stem cells (ADMSCs) and to delineate its underlying mechanisms of action in diabetic nephropathy. Diabetes was induced in adult male Sprague-Dawley rats by streptozotocin (STZ) injection. ADMSCs were administered intravenously 4 weeks after STZ injection and metabolic indices and renal structure were assessed (12 weeks). Markers of diabetes including blood glucose, cholesterol, triglycerides, urea nitrogen and creatinine were measured. Renal pathology, levels of oxidative stress and the expression of pro-inflammatory cytokines and the MAPK signaling pathway members were also determined. Autologous transplantation of ADMSCs significantly attenuated common metabolic disorder symptoms associated with diabetes. Furthermore, ADMSC administration minimized pathological alterations, reduced oxidative damage and suppressed the expression of pro-inflammatory cytokines in the renal tissues of diabetic rats. ADMSC transplantation also decreased the expression of p-p38, p-ERK and p-JNK, which are all important molecules of the MAPK signaling pathway. In conclusion, we provide experimental evidence demonstrating that autologous transplantation of ADMSCs can be used therapeutically to improve metabolic disorder and relieve renal damage induced by diabetes, and that the key mechanisms underlying the positive therapeutic impact of ADMSC treatment in kidneys could be due to the suppression of inflammatory response and oxidative stress. IntroductionDiabetic nephropathy is a major microvascular complication in patients with diabetes and remains the leading cause of chronic kidney disease, accounting for approximately a half of all end-stage renal disease worldwide (1,2). The key pathologic features of diabetic nephropathy include microalbuminurea, mesangial cell (MC) hypertrophy, thickened glomerular and tubular basement membrane, tubulointerstitial fibrosis, and low grade of renal inflammation. It is now well recognized that the pathogenesis of diabetic nephropathy is multifactorial. Over the last decade, diverse pathological mechanisms have been proposed to be involved in the onset and development of diabetic nephropathy, such as genetic and hemodynamic factors, oxidative stress and cytokine signaling (3,4). Nowadays, therapies for diabetic nephropathy have been limited to drugs that improve blood pressure or control blood glucose levels. However, these therapies are not very effective in blocking renal damage and co-treatment with renoprotective drugs often leads to toxicity and reduction in efficacy (5,6). There is thus an imperative need to develop effective therapeutic strategies to preserve normal renal function or to halt the progression of diabetic nephropathy.Mesenchymal stem cells (MSCs) are multipotential nonhematopoietic progenitor cells that can differentiate into a variety of cell types, including osteoblasts, ch...

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Section: Discussionmentioning

confidence: 99%

Autologous transplantation of adipose-derived mesenchymal stem cells ameliorates streptozotocin-induced diabetic nephropathy in rats by inhibiting oxidative stress, pro-inflammatory cytokines and the p38 MAPK signaling pathway

et al. 2012

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“…Another potential problem of using HESC for transplantation is tumourgenicity. Undifferentiated cells that retain pluripotency give rise to tumours known as teratomas in vivo (Mitjavila-Garcia et al, 2005). In addition, the difficulties in obtaining HESCs as well as important ethical concerns make the use of HESCs an improbable candidate for TE (Bobbert, 2006;Lei et al, 2007).…”

Section: Human Embryonic Stem Cells As a Source Of Stem Cells For Tementioning

confidence: 99%

Properties of the amniotic membrane for potential use in tissue engineering

Niknejad

Peirovi²,

Jorjani³

et al. 2008

eCM

654

757

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An important component of tissue engineering (TE) is the supporting matrix upon which cells and tissues grow, also known as the scaffold. Scaffolds must easily integrate with host tissue and provide an excellent environment for cell growth and differentiation. Most scaffold materials are naturally derived from mammalian tissues. The amniotic membrane (AM) is considered an important potential source for scaffolding material. The AM represents the innermost layer of the placenta and is composed of a single epithelial layer, a thick basement membrane and an avascular stroma. The special structure and biological viability of the AM allows it to be an ideal candidate for creating scaffolds used in TE. Epithelial cells derived from the AM have the advantages of stem cells, yet are a more suitable source of cells for TE than stem cells. The extracellular matrix components of the basement membrane of the AM create an almost native scaffold for cell seeding in TE. In addition, the AM has other biological properties important for TE, including anti-inflammatory, anti-microbial, anti-fibrosis, anti-scarring, as well as reasonable mechanical property and low immunogenicity. In this review, the various properties of the AM are discussed in light of their potential use for TE.

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“…Many types of stem cells, including ES cells, iPS cells, and MSCs, have been used for hepatic differentiation. Although ES cells are pluripotent and can efficiently differentiate into DHCs, they have limited biological applications because of concerns over teratoma formation, ethical issues, and immune rejection [12]. Although iPS cells can overcome the limitations of ES cells, they are not suitable for virus-related research because they are generated by permanent infection with viruses carrying several genes associated with reprogramming [38].…”

Section: Discussionmentioning

confidence: 99%

“…MSCs are recognized as a more promising source than ES cells or iPS cells, which can trigger teratoma formation, immunogenicity, and are associated with ethical concerns [12], [13]. Currently, multipotent adipose tissue-derived MSCs (AT-hMSCs) can be differentiated into multiple cells, including adipocytes, osteoblasts, chondrocytes, myocytes, and hepatocytes [14], [15].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-27a Modulates HCV Infection in Differentiated Hepatocyte-Like Cells from Adipose Tissue-Derived Mesenchymal Stem Cells

et al. 2014

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Background and AimsDespite the discovery of hepatitis C virus (HCV) entry factor, the mechanism by which it is regulated by miRNAs remains unclear. Adipose tissue-derived human mesenchymal stem cells (AT-hMSCs) have been widely used for differentiated hepatocyte-like cells (DHCs). Here, we established an in vitro HCV infection model using DHCs from AT-hMSCs and identified miRNAs that modulate HCV infectivity.MethodsAT-hMSCs were differentiated into DHCs using the conditional media, and evaluated for hepatocyte characteristics using RT-PCR, immunocytochemistry, periodic acid-Schiff staining, and a urea synthesis assay. The expression of HCV candidate receptors was also verified using immunocytochemistry. The levels of candidate miRNAs targeting HCV receptors were then determined by relative quantitative RT-PCR (rqRT-PCR). Finally, DHCs were infected using HCVcc and serum from HCV-infected patients, and infectivity of the virus was measured by rqRT-PCR and transmission electron microscopy (TEM).ResultsThe expected changes in morphology, function and hepatic gene expression were observed during hepatic differentiation. Moreover, the expression of candidate HCV entry factors and miR-27a were altered during hepatic differentiation. The infection and replication of HCV occurred efficiently in DHCs treated with HCVcc or infected with serum from HCV-infected patients. In addition, HCV infectivity was suppressed in miR-27a-transfected DHCs, due to the inhibition of LDLR expression by miR-27a.ConclusionsOur results demonstrate that AT-hMSCs are a good source of DHCs, which are suitable for in vitro cultivation of HCV. Furthermore, these results suggest that miR-27a modulates HCV infectivity by regulating LDLR expression.

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Embryonic stem cells: Meeting the needs for cell therapy

Cited by 22 publications

References 61 publications

Autologous transplantation of adipose-derived mesenchymal stem cells ameliorates streptozotocin-induced diabetic nephropathy in rats by inhibiting oxidative stress, pro-inflammatory cytokines and the p38 MAPK signaling pathway

Autologous transplantation of adipose-derived mesenchymal stem cells ameliorates streptozotocin-induced diabetic nephropathy in rats by inhibiting oxidative stress, pro-inflammatory cytokines and the p38 MAPK signaling pathway

Properties of the amniotic membrane for potential use in tissue engineering

MicroRNA-27a Modulates HCV Infection in Differentiated Hepatocyte-Like Cells from Adipose Tissue-Derived Mesenchymal Stem Cells

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