Review Article

Stem Cell Tracking with Nanoparticles for Regenerative Medicine Purposes: An Overview

Table 2

Summary of different in vivo studies performed with nanoparticles used to label stem cells.

StudyExperimental modelNanoparticleStem cellLabeling approachMain results
AnimalTypeTypeDoseSourceType Number

Slotkin et al. 2007 [214]MouseDeveloping central nervous systemQDs2.5 ngMouseNeural stem and progenitor cellsDirect labelingFluorescence imagingNovel in utero electroporation and ultrasound-guided in vivo delivery, QDs are compatible with early mammalian embryonic development

Rosen et al. 2007 [215]RatNormalQDs8.2 nMHumanMSC1 105Fluorescence imagingLong-term tracking technique for at least 8 weeks permits the complete three-dimensional reconstruction of the locations into the heart

Chen et al. 2015 [138]MouseWound healing modelQDs12.5 μg/mLHumanMSC1 105Fluorescence imagingDynamic visualization in vivo of migration to the wound after intravenous injection, treatment of wound with collagen scaffold-SDF-1α enhances the reepithelialization and the neovascularization and accelerates the wound healing

Delcroix et al. 2009 [198]RatLesioned brainSPIO25 μg/mLRatMSC40–100 103Magnetic resonance imagingCell migration toward lesions and description of the long distance migration from the SVZ toward the olfactory bulb through the rostral migratory stream

Guzman et al. 2007 [196]RatHuntington’s disease modelSPIO (Ferumoxides)5 μg/mLHumanCentral nervous system cell1 105Magnetic resonance imagingLong-term survival and differentiation of cells

Hu et al. 2012 [230]RatSpinal cord injurySPIO7 μg Fe/mLHumanMSC4 105Magnetic resonance imaginghUC-MSCs can survive and migrate in the host spinal cord after transplantation, which promote functional recovery after spinal cord injury

Jing et al. 2008 [200]RabbitArticular cartilage defect modelSPIO (ferumoxides)25 μg/mLRabbitMSC1 108Magnetic resonance imagingEngineered autologous MSCs do not actively participate in the repair of articular cartilage defects following intra-articular injection

Amsalem et al. 2007 [231]RatMyocardial infarctionSPIO (ferumoxides)25 μg/mLRatMSC2 106Magnetic resonance imagingMSCs attenuated progressive left ventricular dilatation and dysfunction compared with controls without cells

Chapon et al. 2009 [232]RatMyocardial infarctionSPIO10 μg/mLRatMSC5 105Magnetic resonance imagingAbility to track SCs by noninvasive imaging, and the importance of using multimodal platforms to establish the effect of SCs on cardiac function

Blocki et al. 2015 [233]RatMyocardial infarctionSPIO10 μg/mLRatMSC1 106Magnetic resonance imagingInjectable microcapsules for the delivery overcome current limitations of poor cell retention in cardiac cell-based therapy

Ramos-Gómez et al. 2015 [206]RatParkinson’s disease modelSPIO (different types)50 μg/mLHumanNeuronal line3 105Magnetic resonance imagingFeasibility for long-term tracking, possible internalization of NPs by host microglial cells

Kim et al. 2010 [234]RatLiver cirrhosis modelSilica shell on SPIO (ferumoxides)100 μg/mLHumanMSC3 106Magnetic resonance and fluorescence imagingFeasibility for tracking in liver cirrhosis model

Zhang et al. 2013 [162]MouseStroke modelMesoporous silica core-shell SPIO5–33 μg/mLMouseNeuronal progenitor line1 105Magnetic resonance and fluorescence imagingMonitoring of the cell homing to the ischemic area after intravenously injection

Berman et al. 2011 [235]MouseImmunodeficient and immunocompetentSPIO (BioPAL)25 μg/mLMouseNeuronal progenitor line3 105Magnetic resonance and bioluminescence imagingLive cell proliferation and associated label dilution may dominate contrast clearance as compared with cell death and subsequent transfer and retention of superparamagnetic iron oxide within phagocytes and brain interstitium

Terrovitis et al. 2008 [236]RatMyocardial transplantation modelSPIO (ferumoxides)25 μg/mLRat and humanCardiac-derived stem cell5 105
7.5 105
Magnetic resonance imagingPersistence of significant iron-dependent MRI signal derived from ferumoxide-containing macrophages despite few or no viable stem cells 3 weeks after transplantation

Janowski et al. 2014 [237]HumanPermanent vegetative stateSPIO (ferumoxides)100 μg/mLHumanCord blood nucleated cell3.6 107Magnetic resonance imagingFeasibility of long-term clinical tracking

Boehm-Sturm et al. 2011 [244]MouseCD-1Perfluoropolyether120 mg/mLHumanNeural stem cell1.5 105Magnetic resonance imaging19F MRI can be utilized for tracking human NSCs in brain implantation studies

Jokerst et al. 2012 [211]MouseNormalSilica-coated gold0.0–0.14 nMHumanMSCUnknownPhotoacoustic imagingFeasibility of multimodal approach

Nam et al. 2012 [210]RatNormalGold1012 NPs/mLHumanMSC5 104Photoacoustic imagingMultimodal approach capable of noninvasive, sensitive, quantitative, and longitudinal assessment of stem cell behaviors with high spatial and temporal resolutions at sufficient depths

Ricles et al. 2014 [248]RatHind limb ischemia modelGold1012 NPs/mLRatMSC1 104Photoacoustic imagingSystem capable of monitoring both delivered stem cells and infiltrating macrophages using photoacoustic imaging

Nam et al. 2015 [212]RatCutaneous burn injury modelSilica-coated gold4 107 NPs/
cell
Rat and humanAdipose derived1 106Photoacoustic imagingFeasibility of long-term tracking, ability of multimodal imaging to assess both burn injury and skin tissue regeneration