MR Evaluation of the Glomerular Homing of Magnetically Labeled Mesenchymal Stem Cells in a Rat Model of Nephropathy

Objective: Cell-based therapies are being investigated as an adjunct to IV thrombolysis or mechanical thrombectomy in ischemic stroke. This review summarizes the potential applications as well as challenges of intravascular cell delivery in ischemic stroke. Method:We conducted a search of Medline as well as the clinicaltrials.gov Web site for all ongoing human clinical studies using stem cells in ischemic stroke patients. Result:The pros and cons of the various donor cell types and routes of cell delivery, including intravascular delivery, in ischemic stroke are discussed. In addition, the potential challenges in translation from bench to bedside, the optimal techniques for intravascular cell delivery, and an updated comprehensive list of ongoing clinical trials in ischemic stroke are highlighted. Conclusions:Stem cells have shown a promising role in ischemic stroke, in preclinical studies as well as initial pilot studies. Further studies are needed to assess intravascular cell therapy as a potential adjunct to thrombolysis or mechanical thrombectomy in ischemic stroke. Neurology Cell therapy is emerging as a promising new modality for enhancing neurologic recovery in ischemic stroke.1 Numerous basic science studies have demonstrated positive results in animal models of ischemic stroke following implantation of progenitor cells derived from various sources, including adipose, human fetal/embryonic tissue, bone marrow, peripheral, and umbilical cord blood (figure).2 These animal studies have utilized various methods of cell delivery or implantation (table 1), including direct intracerebral (IC) injection, intracisternal/cerebroventricular (ICV), or intravascular routes of delivery such as IV or intra-arterial (IA) infusion.Methods of cellular delivery and implantation. Intracerebral. Direct injection is invasive, and despite being a precise method of cellular delivery and implantation, it results in a poor distribution of cells in the target lesion.3 Initial pilot human studies investigating stereotactic IC cell implantation in patients with chronic stroke also reported adverse events, including seizures, syncope, asymptomatic subdural hematoma, transient motor worsening, and enhancing lesions on MRI. 4,5Intracisternal/cerebroventricular. The ICV route of cell delivery is less invasive than direct IC implantation but is also associated with variable cell migration to the ischemic site.6,7 In a pilot human study investigating ICV delivery in 10 chronic stroke patients (7 ischemic and 3 hemorrhagic), some patients developed fever and meningeal signs 48 hours after cellular delivery via ICV route. IV.Infusion is the least invasive method, allowing wide distribution of cells with exposure to chemotactic signals that potentially guide them toward the target ischemic lesion. This method, however, results in cells being trapped by peripheral organs, including the lungs, liver, and spleen, thereby limiting potential engraftment in the ischemic lesion in the brain.2 Since patients with ischemic stroke commonly ha...

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“…9,10 Given that IV cell delivery is least invasive, this method of From the Texas Stroke Institute (V.M., V…”

Section: IVmentioning

confidence: 99%

Stem cell therapy in ischemic stroke

et al. 2012

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“…Following iron-oxide labelled MSC introduction via the tail vein into rats, MSC migration to, and retention within, the liver was increased when a circular magnet was placed directly over the liver (Arbab et al, 2004a). This gives rise to the possibility of being able to deliver stem cells to a specific site, which may augment the natural homing of MSC to damaged tissue that has previously been documented (Hauger et al, 2006).…”

Section: Tracking Of Mscmentioning

confidence: 99%

Recent advances into the understanding of mesenchymal stem cell trafficking

et al. 2007

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SummaryThe use of adult stem cells to regenerate damaged tissue circumvents the moral and technical issues associated with the use of those from an embryonic source. Mesenchymal stem cells (MSC) can be isolated from a variety of tissues, most commonly from the bone marrow, and, although they represent a very small percentage of these cells, are easily expandable. Recently, the use of MSC has provided clinical benefit to patients with osteogenesis imperfecta, graft-versushost disease and myocardial infarction. The cellular cues that enabled the MSC to be directed to the sites of tissue damage and the mechanisms by which MSC then exert their therapeutic effect are becoming clearer. This review discusses the relative therapeutic importance of the ability of MSC to differentiate into multiple cell lineages or stimulate resident or attracted cells via a paracrine mode of action. It also reviews recent findings that MSC home to damaged tissues in a similar, but somewhat distinct, manner to that of leucocytes via the utilisation of adhesion molecules, such as selectins and integrins, and chemokines and their receptors in a manner reminiscent of leucocytes trafficking from the blood stream to inflammatory sites.

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“…The efficacy of such therapies could be in part monitored by cellular MRI. Cell tracking of large cohorts of magnetically labeled MSC has been demonstrated in rat models of nephropathy after intravenous [32] and intraarterial [33] injection and after intramyocardial cell injection in a porcine model of myocardial infarction [34]. Furthermore, at least four clinical trials using MRI cell tracking with superparamagnetic iron oxides have been performed with promising results and it is most likely that MSC-based therapies will become more and more popular over the next decades [35,36] This study investigates the possibility of in-vivo single cell detection of MSC by MRI, which would be a valuable technique to track the migration of even small numbers of MSC in living animals and may help to improve the understanding of the timeline of cell-based therapies, the cells immediate and long-term fate as well as the exclusion of graft failure or tumor formation at the injection side [37].…”

mentioning

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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MR Evaluation of the Glomerular Homing of Magnetically Labeled Mesenchymal Stem Cells in a Rat Model of Nephropathy

Abstract: Intravenously injected MSCs specifically home to focal areas of glomerular damage and can be detected at ex vivo MR imaging.

Cited by 127 publications

References 33 publications

Stem cell therapy in ischemic stroke

Stem cell therapy in ischemic stroke

Recent advances into the understanding of mesenchymal stem cell trafficking

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

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