Human Bone Marrow Mesenchymal Stem Cells Accelerate Recovery of Acute Renal Injury and Prolong Survival in Mice

Morigi, Marina; Introna, Martino; Imberti, Barbara; Corna, Daniela; Abbate, Mauro; Rota, Cinzia; Rottoli, Daniela; Benigni, Ariela; Perico, Norberto; Zoja, Carla; Rambaldi, Alessandro; Remuzzi, Andrea; Remuzzi, Giuseppe

doi:10.1634/stemcells.2007-0795

Cited by 351 publications

(301 citation statements)

References 60 publications

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“…Administration of heterologous MSCs confers a protective effect against AKI and a functional improvement in chronic kidney disease (CKD), but the explanation for these beneficial effects is still debated. Initially, it was thought that MSCs home to the kidney and replace damaged renal cells; in particular, in AKI induced by cisplatin 22,23 and glycerol, 24,25 a tubular engraftment of the injected MSCs has been observed. Subsequently, in the ischemia-reperfusion injury (IRI) model, evidence of differentiation of MSCs directly into tubular cells was not been detected, 26,27 and these data suggested that the MSCs do not replace renal tubular cells but mitigate injury by providing a paracrine support to the repair of injured ©2 0 1 1 L a n d e s B i o s c i e n c e .…”

Section: Effect Of Mesenchymal Stem Cell-derived Mvs In Renal Regenermentioning

confidence: 99%

The role of microvesicles in tissue repair

Bruno²,

et al. 2011

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Section: Effect Of Mesenchymal Stem Cell-derived Mvs In Renal Regenermentioning

confidence: 99%

The role of microvesicles in tissue repair

Bruno²,

et al. 2011

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“…Multipotent mesenchymal stromal cells (MSC), also known as mesenchymal stem cells [14], are bone marrow-derived precursor cells with the potential to differentiate into different mesenchymal lineages, such as adipocytes, chondroblasts and osteoblasts [15]. Because of their differentiation potential, MSC are of particular interest for cell-based therapies in different acute disorders such as myocardial infarction and acute renal failure [16,17]. Furthermore, MSC are known for their immunosuppressive and immunomodulatory potential during stem cell transplantation [18 -21].…”

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confidence: 99%

Magnetic Resonance Imaging of Single Co-Labeled Mesenchymal Stromal Cells after Intracardial Injection in Mice

Salamon

Wicklein

Didié

et al. 2014

Fortschr Röntgenstr

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Ziel: Etablierung einer Doppelmarkierung mesenchymaler Stromazellen (MSZ) zur in-vivo Detektion einzelner MSZ mittels MRT und zur histologischen Validierung. Material und Methoden: Murine MSZ wurden mit fluoreszierenden Eisenmikropartikeln und Carboxyfluorescein Succinimidyl Ester (CFSE) markiert. Der zelluläre Eisengehalt wurde mittels Atomabsorptionsspektrometrie bestimmt. Zellprolieferation und Expression charakteristischer Oberflächenmarker wurden mittels Durchflusszytometrie bestimmt. Die chondrogene Differenzierungskapazität wurde überprüft. Verschiedene Zellanzahlen (n1 = 5000, n2 = 15 000, n3 = 50 000) wurden bei 12 Mäusen in den linken Herzventrikel injiziert. Es erfolgte die sequenzielle MRT der Tiere an einem klinischen 3.0 T MRT. Zur histologischen Validierung wurden Kryostatschnitte fluoreszensmikroskopisch untersucht. Ergebnisse: Die magnetische und fluoreszierende Doppelmarkierung von MSZ wurde etabliert (mittlerer zellulärer Eisengehalt 23,6 ± 4,3 pg). Durchflusszytometrisch zeigten sich ähn-liche Zellprolieferationsraten und Rezeptorexpressionsprofile von markierten und unmarkierten MSZ. Die chondrogene Differenzierung der doppelt markierten MSZ wurde verifiziert. Nach Zellinjektion zeigten sich im MRT multiple Signalauslöschungen im Hirn und geringer in der Niere. Im Hirn fanden sich durchschnittlich 4,6 ± 1,2 (n1), 9,0 ± 3,6 (n2) und 25,0 ± 1,0 (n3) Signalauslöschungen pro Schicht. Durchschnittlich fanden sich 8,7 ± 3,1 (n1), 22,0 ± 6,1 (n2) und 89,8 ± 6,5 (n3) Zellen pro korrespondierendem Kryostatschnitt. Die statistische Korrelation der mittels MRT detektierten Signalauslöschungen und der histologisch nachgewiesenen Zellen ergab einen Korrelationskoeffizienten von r = 0,91. Schlussfolgerung: Die Studie zeigt die erfolgreiche magnetische und fluoreszierende DoppelmarkieAbstract ! Purpose: The aim of this study was to establish co-labeling of mesenchymal stromal cells (MSC) for the detection of single MSC in-vivo by MRI and histological validation. Materials and Methods: Mouse MSC were co-labeled with fluorescent iron oxide micro-particles and carboxyfluorescein succinimidyl ester (CFSE). The cellular iron content was determined by atomic absorption spectrometry. Cell proliferation and expression of characteristic surface markers were determined by flow cytometry. The chondrogenic differentiation capacity was assessed. Different amounts of cells (n1 = 5000, n2 = 15 000, n3 = 50 000) were injected into the left heart ventricle of 12 mice. The animals underwent sequential MRI on a clinical 3.0 T scanner (Intera, Philips Medical Systems, Best, The Netherlands). For histological validation cryosections were examined by fluorescent microscopy. Results: Magnetic and fluorescent labeling of MSC was established (mean cellular iron content 23.6 ± 3 pg). Flow cytometry showed similar cell proliferation and receptor expression of labeled and unlabeled MSC. Chondrogenic differentiation of labeled MSC was verified. After cell injection MRI revealed multiple signal voids in the brain and fewer signal voids...

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“…What is perhaps most pertinent, however, is that inflammatory demyelinated lesions were obvious throughout the CNS at this stage (day 50) and yet few or no hMSCs were disclosed. Rejection would be unlikely in view of the recognised immune suppressive effects of these cells [12]; others have likewise found no rejection of human MSCs in rodent recipients [8,17].…”

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confidence: 99%

Human mesenchymal stem cells abrogate experimental allergic encephalomyelitis after intraperitoneal injection, and with sparse CNS infiltration

Gordon

Pavlovska

Glover³

et al. 2008

Neuroscience Letters

113

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Multiple sclerosis is a currently incurable inflammatory demyelinating syndrome. Recent reports suggest that bone marrow derived mesenchymal stem cells may have therapeutic potential in experimental models of demyelinating disease, but various alternative mechanisms, ranging from systemic immune effects to local cell replacement, have been proposed. Here we used intraperitoneal delivery of human mesenchymal stem cells to help test (a) whether human cells can indeed suppress disease, and (b) whether CNS infiltration is required for any beneficial effect. We found pronounced amelioration of clinical disease but profoundly little CNS infiltration. Our findings therefore help confirm the therapeutic potential of mesenchymal stem cells, show that this does indeed extend to human cells, and are consistent with a peripheral or systemic immune effect of human MSCs in this model. Keywords Mesenchymal stem cells; Multiple sclerosis; Experimental allergic encephalomyelitisMultiple sclerosis is an acquired inflammatory demyelinating syndrome of unknown cause, and which is currently incurable. In many individuals, progressive disability occurs during the course of the disease, as a consequence of irreversible CNS damage. The ineffectiveness of current therapies has emphasised the importance of novel treatment approaches, and stem cells are widely held as having particular promise.Bone marrow derived mesenchymal stem cells can proliferate substantially, and can differentiate into cells of all three germ cell layers, including neural cells; moreover they are relatively accessible, could be used for autologous therapy, and are capable of entering the CNS (particularly when damaged) from the circulation [6,11]. They are therefore considered good candidates for early clinical stem cell therapeutic studies.Recently, reports have appeared suggesting that bone marrow-derived cells can ameliorate toxic and inflammatory experimental demyelinating disease following intravenous delivery [1,3,5,7,[13][14][15][16]. However, whether this effect is achieved through cell replacement and

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Human Bone Marrow Mesenchymal Stem Cells Accelerate Recovery of Acute Renal Injury and Prolong Survival in Mice

Abstract: ABSTRACT

Cited by 351 publications

References 60 publications

The role of microvesicles in tissue repair

The role of microvesicles in tissue repair

Magnetic Resonance Imaging of Single Co-Labeled Mesenchymal Stromal Cells after Intracardial Injection in Mice

Human mesenchymal stem cells abrogate experimental allergic encephalomyelitis after intraperitoneal injection, and with sparse CNS infiltration

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