In Vitro Differentiation of MSC into Cells with a Renal Tubular Epithelial-Like Phenotype

Singaravelu, Kurinji; Padanilam, Babu J.

doi:10.1080/08860220902928981

Cited by 54 publications

(39 citation statements)

References 49 publications

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“…The reason is that differentiation of BM-MSCs needs stimulation from the cytokines secreted by damaged visceral organs. However, these cytokines are not secreted by the normal kidney tissues (Singaravelu and Padanilam, 2009).…”

Section: Discussionmentioning

confidence: 99%

“…The role of cytokines in organ I/R injury has gained increased attention as a result of many studies on the cytokine network. BM-MSCs possess powerful secretory functions, which assist in AKI repair through their paracrine effect (Di Nicola et al, 2002;Singaravelu and Padanilam, 2009). In the present study, the supernatant of mBM-MSCs grown in low-sugar DMEM was found to contain the cytokines BMP-7, HGF, and VEGF, all of which can facilitate the repair of renal injury (Hruska, 2002).…”

Section: Discussionmentioning

confidence: 99%

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Effect of erythropoietin on mesenchymal stem cell differentiation and secretion in vitro in an acute kidney injury microenvironment

Liu¹,

Tian²,

Wang³

et al. 2013

Genet. Mol. Res.

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ABSTRACT.We investigated the effect of erythropoietin (EPO) on differentiation and secretion of bone marrow-derived mesenchymal stem cells in an acute kidney injury microenvironment. Acute kidney injury mouse models were prepared. Both renal cortices were then immediately collected to produce the ischemia/reperfusion kidney homogenate supernatant. The morphological and ultrastructural changes in the cells were observed using an inverted microscope and a transmission electron microscope. Cytokeratin-18 was detected using flow cytometry. Bone morphogenetic protein-7 levels, hepatocyte growth factor, and vascular endothelial growth factor in the culture medium were detected using an enzyme-linked immunosorbent assay. The cells had high CD29 and CD44 expression, as well as low CD34 and CD45 expression. More round and oval cells with cobble-like appearances were observed after EPO treatment. In addition, an increase in the number of rough endoplasmic reticula, lysosomes, and mitochondria was observed in the cytoplasm; the intercellular junction peculiar to epithelial cells was also seen on the cell surface. After treatment with ischemia/reperfusion kidney homogenate supernatant, cytokeratin-18 expression increased significantly and EPO could magnify its expression. Bone morphogenetic protein-7 levels, hepatocyte growth factor, and vascular endothelial growth factor levels after treatment with ischemia/ reperfusion kidney homogenate supernatant significantly decreased, whereas EPO increased the cytokine secretion. The acute kidney injury microenvironment can induce the bone marrow-derived mesenchymal stem cells to partially differentiate into renal tubular epithelium-shaped cells, but weaken their secretion function. EPO intervention can boost up their differentiation function and reverse their low secretion effect.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effect of erythropoietin on mesenchymal stem cell differentiation and secretion in vitro in an acute kidney injury microenvironment

Liu¹,

Tian²,

Wang³

et al. 2013

Genet. Mol. Res.

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“…Because vimentin is usually not expressed in differentiated tubular cells, the stable expression of this marker (Figure 2, D and H) in our culture highlights that these cells are not fully differentiated and that they are closer to progenitor cells. At day 21, we detected the expression of cadherin-16/KSP by real-time PCR ( Figure 2F) and immunofluorescence analysis 24 ( Figure 2I). Cadherin-16 is expressed specifically in renal tubular cells, and in vivo its expression starts at the S-shaped body stage, around E14.5 in mice.…”

Section: Gpscs Differentiate Into Renal Tubular Cells In Vitromentioning

confidence: 99%

Renal Cells from Spermatogonial Germline Stem Cells Protect against Kidney Injury

Chiara

Fagoonee

Bruno

et al. 2014

Journal of the American Society of Nephrology

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Spermatogonial stem cells reside in specific niches within seminiferous tubules and continuously generate differentiating daughter cells for production of spermatozoa. Although spermatogonial stem cells are unipotent, these cells are able to spontaneously convert to germline cell-derived pluripotent stem cells (GPSCs) in vitro. GPSCs have many properties of embryonic stem cells and are highly plastic, but their therapeutic potential in tissue regeneration has not been fully explored. Using a novel renal epithelial differentiation protocol, we obtained GPSC-derived tubular-like cells (GTCs) that were functional in vitro, as demonstrated through transepithelial electrical resistance analysis. In mice, GTCs injected after ischemic renal injury homed to the renal parenchyma, and GTC-treated mice showed reduced renal oxidative stress, tubular apoptosis, and cortical damage and upregulated tubular expression of the antioxidant enzyme hemeoxygenase-1. Six weeks after ischemic injury, kidneys of GTC-treated mice had less fibrosis and inflammatory infiltrate than kidneys of vehicle-treated mice. In conclusion, we show that GPSCs can be differentiated into functionally active renal tubular-like cells that therapeutically prevent chronic ischemic damage in vivo, introducing the potential utility of GPSCs in regenerative cell therapy. AKI is a common complication characterized by a rapid reduction in kidney function that results in failure to maintain fluid. AKI is a potentially reversible disease. However, some patients recover incompletely from AKI, and these patients either continue undergoing dialysis or progress to CKD. Moreover, development of CKD can lead to ESRD. One of the main causes of AKI is ischemia/reperfusion injury (IRI). 1 IRI is a pathologic condition characterized by an initial restriction of blood supply followed by the subsequent restoration of perfusion and concomitant reoxygenation that is frequently associated with an exacerbation of tissue injury and a strong inflammatory response. 2 The cells within the renal parenchyma that suffer the most damage upon kidney ischemia are the proximal tubular cells. This is likely due to the presence of a brush border on these cells that increases cell surface area and sensitizes them to damage.The recent discovery of the ability to reprogram adult cells into pluripotent stem cells (iPSCs) has profound therapeutic implications for diseases involving tissue damage and degeneration. Derivation of pluripotent stem cells from an adult source avoids several ethical concerns of obtaining such cells from embryos. However, efficient generation of iPSCs typically requires transduction of cells with reprogramming factors, including potent proto-oncogenes that can limit their therapeutic uses. 3 The existence of inherent epigenetic differences between iPSCs and regular embryonic stem cells (ESCs) can adversely affect iPSCs functionality. 4,5

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“…MSC therapy reportedly ameliorates kidney injury, accelerates tubule proliferation, and restores renal function. 4,5 However, many difficulties must be overcome to successfully implement MSC therapy, one of which is the scarcity of MSCs in injured tissues after systematic infusion. [6][7][8] The insufficient homing of MSCs and the inability to drive them to the damaged kidney tissues have become a major barrier to the effective implementation of MSC therapy.…”

Section: Introductionmentioning

confidence: 99%

Ultrasound-targeted stromal cell-derived factor-1-loaded microbubble destruction promotes mesenchymal stem cell homing to kidneys in diabetic nephropathy rats

Wu¹,

Li²,

Gong³

et al. 2014

IJN

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Mesenchymal stem cell (MSC) therapy has been considered a promising strategy to cure diabetic nephropathy (DN). However, insufficient MSCs can settle in injured kidneys, which constitute one of the major barriers to the effective implementation of MSC therapy. Stromal cell-derived factor-1 (SDF-1) plays a vital role in MSC migration and involves activation, mobilization, homing, and retention, which are presumably related to the poor homing in DN therapy. Ultrasound-targeted microbubble destruction has become one of the most promising strategies for the targeted delivery of drugs and genes. To improve MSC homing to DN kidneys, we present a strategy to increase SDF-1 via ultrasound-targeted microbubble destruction. In this study, we developed SDF-1-loaded microbubbles (MB SDF-1 ) via covalent conjugation. The characterization and bioactivity of MB SDF-1 were assessed in vitro. Target release in the targeted kidneys was triggered with diagnostic ultrasound in combination with MB SDF-1 . The related bioeffects were also elucidated. Early DN was induced in rats with streptozotocin. Green fluorescent protein-labeled MSCs were transplanted intravenously following the target release of SDF-1 in the kidneys of normal and DN rats. The homing efficacy was assessed by detecting the implanted exogenous MSCs at 24 hours. The in vitro results showed an impressive SDF-1 loading efficacy of 79% and a loading content of 15.8 μg/mL. MB SDF-1 remained bioactive as a chemoattractant. In the in vivo study, SDF-1 was successfully released in the targeted kidneys. The homing efficacy of MSCs to DN kidneys after the target release of SDF-1 was remarkably ameliorated at 24 hours compared with control treatments in normal rats and DN rats. In conclusion, ultrasound-targeted MB SDF-1 destruction could promote the homing of MSCs to early DN kidneys and provide a novel potential therapeutic approach for DN kidney repair.

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In Vitro Differentiation of MSC into Cells with a Renal Tubular Epithelial-Like Phenotype

Cited by 54 publications

References 49 publications

Effect of erythropoietin on mesenchymal stem cell differentiation and secretion in vitro in an acute kidney injury microenvironment

Effect of erythropoietin on mesenchymal stem cell differentiation and secretion in vitro in an acute kidney injury microenvironment

Renal Cells from Spermatogonial Germline Stem Cells Protect against Kidney Injury

Ultrasound-targeted stromal cell-derived factor-1-loaded microbubble destruction promotes mesenchymal stem cell homing to kidneys in diabetic nephropathy rats

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