Mesenchymal Stem Cells in Renal Function Recovery after Acute Kidney Injury: Use of a Differentiating Agent in a Rat Model

Manna, Gaetano La; Bianchi, Francesca; Cappuccilli, Maria; Cenacchi, Giovanna; Tarantino, Lucia; Pasquinelli, Gianandrea; Valente, Sabrina; Bella, Elena Della; Cantoni, Silvia; Cavallini, Claudia; Neri, Flavia; Tsivian, Matvey; Nardo, Bruno; Ventura, Carlo; Stefoni, Sergio

doi:10.3727/096368910x543394

Cited by 39 publications

(50 citation statements)

References 52 publications

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“…The growing consensus is that this protective function acts predominantly through endocrine or paracrine factors released by MSC (Togel et al, 2005;Cao et al, 2010). The incidence of engraftment and differentiation of MSC into kidney component cells is variable (La Manna et al, 2011). Their ability to differentiate into kidney component cells, such as mesangial cells, as shown here opens up possibilities in adult stem cell differentiation.…”

Section: Discussionmentioning

confidence: 90%

In vitro differentiation of mesenchymal stem cells into mesangial cells when co‐cultured with injured mesangial cells

Wong

Tan

Cheong

2014

Cell Biology International

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Mesangial cells are one of the three major cell types of the kidney glomerulus that provide physical support for the glomerular capillary lumen of the kidney. Loss of mesangial cells due to pathologic conditions, such as glomerulonephritis and diabetic nephropathy, can impair renal function. Mesenchymal stem cells (MSC) are attractive candidates for kidney repair therapy since they can enhance recovery and protect against kidney failure. MSC can differentiate into mesangial cells in vivo. We have investigated the ability of MSC to differentiate into mesangial cells in vitro; they were co-cultured with oxidant-injured mesangial cells before being analysed by flow cytometry and for contractility. MSC co-cultured with injured mesangial cells had a mesangial cell-like morphology and contracted in response to angiotensin II. They expressed CD54(-) CD62E(+) in direct contrast to the CD54(+) CD62E(-) of pure MSC. In conclusion, MSC can differentiate into mesangial cells in vitro when co-cultured with injured mesangial cells.

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Section: Discussionmentioning

confidence: 90%

In vitro differentiation of mesenchymal stem cells into mesangial cells when co‐cultured with injured mesangial cells

Wong

Tan

Cheong

2014

Cell Biology International

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“…The hyaluronan monoesters with butyric acid (HB) show significant properties to induce metanephric differentiation, formation of capillarylike structures, and secretion of angiogenic cytokines in vitro. In vivo infusion of human mesenchymal stem cells from fetal membranes (FMhMSCs) in AKI rat models after pre-treatment with HB reduces inflammation and accelerates renal function recovery [35] . In addition to MSCs treatment, other molecules, such as NGAL, should be used to regulate the immune response to inflammation and facilitate renal functioning [36] .…”

Section: Mechanisms Of Renoprotection In Aki Models: the Paracrine Acmentioning

confidence: 99%

Potential advantages of acute kidney injury management by mesenchymal stem cells

Bianchi¹,

Sala²,

Donadei³

et al. 2014

WJSC

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Core tip: Mesenchymal stem cells (MSCs) may have an important therapeutic potential in acute kidney injury management. A body of evidence has demonstrated that MSCs act through a paracrine/endocrine secretion of soluble factors and microvesicles. We summarize preclinical studies and ongoing clinical trials that evaluate the role of MSCs in restoring kidney function. We critically explain the current concerns about the use of MSCs and microvesicles that limit their applications in clinical trials. Then, we propose the future directions that could lead to extend MSCs use in humans.Bianchi F, Sala E, Donadei C, Capelli I, La Manna G. reperfusion injury (IRI) is a major cause of AKI, and it is characterized by acute tubular injury and rapid renal dysfunction, generally caused by ischemic or toxic insults [1][2][3] . The kidney undergoing IRI presents an extensive and complex inflammatory/oxidative stress response, that may result in fibroblast proliferation and excessive deposition of extracellular matrix and has been recognized as a major contributor to end-stage kidney disease [4] . Although many efforts have been made to deal with this problem, such as new drugs and modern dialysis techniques, innovative interventions beyond supportive therapy are not available yet [5] ; therefore, a potent therapeutic intervention for ischemia AKI is imperative. In recent years, a promising approach to manage renal IRI is the use of mesenchymal stem cells (MSCs). Their use in treating different kind of diseases as immunological, vascular, cardiac and renal diseases has been extensively explored [6,7] . MSCs can be isolated from various sources, such as bone marrow or adipose tissue, but other organs have their own niches of MSC-like cells, such as the kidney. Besides their broad distribution in the body and an easy isolation, the interest in MSC was originally raised by their capacity to differentiate into other cell types, suggesting that they could be a source of healthy cells to repair/replace injured tissue [8] .There is evidence from both in vitro studies and animal models of AKI that MSCs can promote regenerative responses in the injured kidney, leading to tissue repair and improvement of renal function [9][10][11] . These beneficial effects have been initially ascribed to the trans-differentiation of MSCs into organ specific cells. However, at least in the kidney, this is a very rare event and the kidneyprotective effects of MSCs have been attributed mainly to paracrine mechanisms [12] . This review will focus on the application of cell therapy in AKI, and it will summarize the recent preclinical and clinical results about the use of MSCs in renal IRI (Figure 1). THERAPEUTIC POTENTIAL OF MESENCHYMAL STEM CELLSMesenchymal stem cells are undifferentiated adult stem cells derived from mesodermal embryonic layer that can differentiate into a broad range of different mesenchymal tissues, including cartilage, bone, muscle, stroma, fat, tendon, and other connective tissues [13] . These cells have been originally isolated f...

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“…Previous studies have shown that mesenchymal stem cells (MSCs) from different sources, including human bone marrow, cord blood, embryo and fetal membranes can be applied in tissue repair, such as promoting recovery from acute kidney injury (AKI) induced by various causes [1-4]. Similarly, our laboratory has demonstrated that MSCs derived from human umbilical cord and rat bone marrow mesenchymal stem cells can ameliorate ischemia/reperfusion-induced AKI and mouse hepatic injury [5-8].…”

Section: Introductionmentioning

confidence: 99%

Exosomes released by human umbilical cord mesenchymal stem cells protect against cisplatin-induced renal oxidative stress and apoptosis in vivo and in vitro

et al. 2013

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IntroductionAdministration of bone marrow mesenchymal stem cells (MSCs) or secreted microvesicles improves recovery from acute kidney injury (AKI). However, the potential roles and mechanisms are not well understood. In the current study, we focused on the protective effect of exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-ex) on cisplatin-induced nephrotoxicity in vivo and in vitro.MethodsWe constructed cisplatin-induced AKI rat models. At 24 h after treatment with cisplatin, hucMSC-ex were injected into the kidneys via the renal capsule; human lung fibroblast (HFL-1)-secreted exosomes (HFL-1-ex) were used as controls. All animals were killed at day 5 after administration of cisplatin. Renal function, histological changes, tubular apoptosis and proliferation, and degree of oxidative stress were evaluated. In vitro, rat renal tubular epithelial (NRK-52E) cells were treated with or without cisplatin and after 6 h treated with or without exosomes. Cells continued to be cultured for 24 h, and were then harvested for western blotting, apoptosis and detection of degree of oxidative stress.ResultsAfter administration of cisplatin, there was an increase in blood urea nitrogen (BUN) and creatinine (Cr) levels, apoptosis, necrosis of proximal kidney tubules and formation of abundant tubular protein casts and oxidative stress in rats. Cisplatin-induced AKI rats treated with hucMSC-ex, however, showed a significant reduction in all the above indexes. In vitro, treatment with cisplatin alone in NRK-52E cells resulted in an increase in the number of apoptotic cells, oxidative stress and activation of the p38 mitogen-activated protein kinase (p38MAPK) pathway followed by a rise in the expression of caspase 3, and a decrease in cell multiplication, while those results were reversed in the hucMSCs-ex-treated group. Furthermore, it was observed that hucMSC-ex promoted cell proliferation by activation of the extracellular-signal-regulated kinase (ERK)1/2 pathway.ConclusionsThe results in the present study indicate that hucMSC-ex can repair cisplatin-induced AKI in rats and NRK-52E cell injury by ameliorating oxidative stress and cell apoptosis, promoting cell proliferation in vivo and in vitro. This suggests that hucMSC-ex could be exploited as a potential therapeutic tool in cisplatin-induced nephrotoxicity.

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Mesenchymal Stem Cells in Renal Function Recovery after Acute Kidney Injury: Use of a Differentiating Agent in a Rat Model

Cited by 39 publications

References 52 publications

In vitro differentiation of mesenchymal stem cells into mesangial cells when co‐cultured with injured mesangial cells

In vitro differentiation of mesenchymal stem cells into mesangial cells when co‐cultured with injured mesangial cells

Potential advantages of acute kidney injury management by mesenchymal stem cells

Exosomes released by human umbilical cord mesenchymal stem cells protect against cisplatin-induced renal oxidative stress and apoptosis in vivo and in vitro

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