|Year : 2016 | Volume
| Issue : 3 | Page : 108-113
Tracking mesenchymal stem cells using magnetic resonance imaging
Jens T Rosenberg1, Xuegang Yuan2, Samuel Grant1, Teng Ma3
1 Department of Chemical and Biomedical Engineering, FAMU-FSU College of Engineering, Florida State University; The National High Magnetic Field Laboratory, Florida State University, Tallahassee, FL 32310, USA
2 The National High Magnetic Field Laboratory, Florida State University, Tallahassee, FL 32310, USA
3 Department of Chemical and Biomedical Engineering, FAMU-FSU College of Engineering, Florida State University, Tallahassee, FL 32310, USA
|Date of Submission||04-Aug-2016|
|Date of Decision||05-Aug-2016|
|Date of Acceptance||30-Aug-2016|
|Date of Web Publication||18-Oct-2016|
Department of Chemical and Biomedical Engineering, 2525 Pottsdamer St., Room 131A, FL
Source of Support: None, Conflict of Interest: None
Recent translational studies in the fields of tissue regeneration and cell therapy have characterized mesenchymal stem cells (MSCs) as a potentially effective and accessible measure for treating ischemic cerebral and neurodegenerative disorders such as stroke, Parkinson's disease, and amyotrophic lateral sclerosis. Developing more efficient cell tracking techniques bear the potential to optimize MSC transplantation therapies by providing a more accurate picture of the fate and area of effect of implanted cells. Currently, determining the location of transplanted MSCs involves a histological approach, but magnetic resonance imaging (MRI) presents a noninvasive paradigm that permits repeat evaluations. To visualize MSCs using MRI, the implanted cells must be treated with an intracellular contrast agent. These are commonly paramagnetic compounds, many of which are based on superparamagnetic iron oxide (SPIO) nanoparticles. Recent research has set out characterize the effects of SPIO-uptake on the cellular activity of in vitro human MSCs and the resultant influence that respective SPIO concentration has on MRI sensitivity. As these studies reveal, SPIO-uptake has no effect on the cellular processes of proliferation and differentiation while producing high contrast MRI signals. Moreover, transplantation of SPIO-labeled MSCs in animal models encouragingly showed no loss in MRI contrast, suggesting that SPIO labeling may be an appealing regime for lasting MRI detection. This study is a review article. Referred literature in this study has been listed in the reference part. The datasets supporting the conclusions of this article are available online by searching the PubMed. Some original points in this article come from the laboratory practice in our research centers and the authors' experiences.
Keywords: Cell tracking, human mesenchymal stem cells, hypoxia, ischemia, magnetic resonance imaging, superparamagnetic iron oxide
|How to cite this article:|
Rosenberg JT, Yuan X, Grant S, Ma T. Tracking mesenchymal stem cells using magnetic resonance imaging. Brain Circ 2016;2:108-13
| Introduction|| |
Recent translational studies in the fields of tissue regeneration and cell therapy have characterized mesenchymal stem cells (MSCs) as a potentially effective and accessible measure for treating ischemic cerebral and neurodegenerative disorders such as stroke, Parkinson's disease, and amyotrophic lateral sclerosis.,,,,,,,,, Commonly isolated from bone marrow, MSCs are a type of multipotent progenitor cell responsible for the repair and replacement of tissues with mesenchymal origins, such as cartilage, adipose, and bone., These cells are readily obtained and exhibit an ease of expansion while also retaining the facility to differentiate into a variety of cellular phenotypes, including chondrocytes, osteoblasts, and neural cells.,, MSCs are appealing not only for their potential to differentiate but also because they are known to produce extracellular stimulatory factors that mollify inflammatory conditions as well as factors that promote neuronal growth when implanted within damaged neural cultures. In fact, the weight of experimental evidence has begun to suggest that the primary role of MSCs may not be to serve as direct replacement cells for injured tissues but rather to generate a conducive microenvironment for tissue regeneration through the secretion of trophic factors. These beneficial properties considered in light of the ability of MSCs to cross the blood–brain barrier afford this cell type immense therapeutic potential., Specifically, the neuroprotective, anti-inflammatory, and pro-angiogenic properties of MSCs indicate that their most effective use may be in the repair and regeneration of neural tissues.,,,,,,,,,,, Notably, MSC transplantation in ischemic animal models induced by middle cerebral artery occlusions (MCAO) and cardiac arrest resulted in significant therapeutic benefits, including lesion volume reductions and cognitive improvements.,,,, However, despite the promise of MSC-based therapies, a number of obstacles must still be overcome for them to achieve clinical success, including the improvement of cell survival and delivery.
Developing more efficient cell tracking techniques bears the potential to optimize MSC transplantation therapies by providing a more accurate picture of the fate of the implanted cells together with potential impact on the lesioned area. Currently, determining the location of transplanted MSCs involves a histological approach, but magnetic resonance imaging (MRI) presents a noninvasive paradigm that permits repeat evaluations.,,,,, To visualize MSCs using MRI, the implanted cells must be treated with an intracellular contrast agent. These are commonly paramagnetic compounds, many of which are based on superparamagnetic iron oxide (SPIO) nanoparticles. SPIOs are nano-sized iron oxides which form single magnetic domains and are fabricated with a surrounding low molecular coating of dextran or carboxydextran. SPIOs induce dephasing of proximal 1 H spins when exposed to an external magnetic field due to susceptibility effects. It results in signal loss in and around the location of the particle, increasing the contrast and improving the detectability of cells labeled with these compounds. Accordingly, SPIOs are T2 or T2* agents. While previous work has indicated that SPIOs are biologically harmless, the methods used to encourage their uptake and the concentration of the transfected SPIO differ to a significant degree across studies.,, In some cases, this inconsistency has led to conflicting results, such as those produced using SPIO labeling in human MSC (hMSC) osteogenic differentiation.,, For these reasons, the long-term effects of SPIO labeling across various dosages and durations must be examined to determine if SPIOs affect the potential for differentiation and/or survival of hMSCs.
| The Concentration of Transfected Superparamagnetic Iron Oxides Affects the Magnetic Resonance Imaging Sensitivity and Potential for Cytotoxic Damage of Labeled Human Mesenchymal Stem Cells|| |
A recent study by Rosenberg et al. set out to characterize the effects of SPIO-uptake on the cellular activity of in vitro hMSCs and the resultant influence that respective SPIO concentration has on MRI sensitivity. Importantly, cells were transfected via an acute exposure (6-h) to varying concentrations of SPIO without the use of transfection agents or penetrating peptides. Cells were then cultured and allowed to proliferate for up to 14-d, wherein the long-term cell viability, proliferation, and MRI sensitivity of these cultures were investigated. To determine whether SPIOs might encourage further cytotoxicity in already cytotoxic sites of ischemic injury, SPIO loading in hMSCs was examined in low-serum, hypoxic cultures as well. In addition, the researchers employed an animal model, MCAO rats, to evaluate the localization of MSCs using MRI and histological techniques. The results of the study suggest that cellular processes such as proliferation and differentiation were not influenced by any of the SPIO concentrations examined during a cell culturing period of 14 days. In addition, a 6 h incubation time and low SPIO exposure level were sufficient for long-term MRI detectability. Notably, high SPIO exposure opened a cell to higher incidence of calcification and cytotoxicity within in vitro ischemic conditions than did low SPIO exposures. Transplantation of SPIO labeled MSCs in animal models encouragingly showed no loss in MRI contrast, suggesting that SPIO labeling may be an appealing regime for lasting MRI detection, with the corollary that high concentrations of SPIO may impact the survival of MSCs in ischemic implantation areas.
| Discussion|| |
SPIOs are regularly used as intracellular contrast agents in hMSC labeling and are considered to be appreciably biocompatible, effecting minimal influence on crucial cellular processes such as differentiation and proliferation.,,,, However, while many studies have examined the success of short-term detection of SPIOs between 0 and 72 h after transfection, few have examined the long-term MRI detectability of SPIO-exposed hMSCs., 30, ,, Importantly, hMSCs may survive more than 7 days after implantation, so long-term studies are important to understanding the full potential of SPIO detection and the efficacy of tracking hMSCs over the course of chronic treatments., Moreover, hMSCS are increasingly being used to treat ischemic and cerebral injuries on account of their anti-inflammatory and pro-angiogenic properties.,,,, Nevertheless, how nutritionally deficient and hypoxic molecular microenvironments at sites of ischemic insult may affect the detectability and survival of SPIO-labeled hMSCs has yet to be resolved. Determining the relative MRI detectability of SPIO-labeled hMSCs after 7 days and their viability within ischemic microenvironments is vital to advancing the current state of hMSC treatments.
| The Relationship between Superparamagnetic Iron Oxide Uptake AndIn Vitro Magnetic Resonance Imaging Detectability|| |
The results of previous studies and recent work by Rosenberg et al. suggest that SPIO incorporation in hMCS is exposure-dependent.,,, That is to say, hMSCs incubated in SPIO-infused media exhibited a near linear increase in the amount of SPIO they incorporated as anticipated by the relative concentrations of SPIO in their culture media. Importantly, this result indicates that SPIO-induction in hMSCS is possible without chemical modification of SPIOs or hMSCs. In previous studies, to improve the success of their incorporation in hMSCS, SPIOS have been modified with cell-specific receptors, poly-L-lysine (PLL), dextran, liposomes, lectin, chitosan, starch, and polystyrene.,,,,,,,,, The studies by Rosenberg et al. and other recent investigations reveal that modification of SPIOs with transfection factors or CPP is inessential. Moreover, media-based induction may work to preserve hMSCS functionality, as different CPPs such as PLL are noted as having the potential to alter or interfere with natural cell function by coating cell surfaces.
Defining the specific concentration of SPIO that both allows for long-term detectability while conserving normal cell behavior will help determine the optimal method for media-based labeling of hMSCs. As evidenced by the MRI results in the investigation by Rosenberg et al, relatively low initial internalized iron concentrations enable hMSC detection over a complete 14-day detection period. Moreover, the highest SPIO concentration, while producing the greatest initial contrast in cell imaging, appeared to stimulate an increase in cell proliferation. Previous studies have demonstrated that SPIOs may affect the cell cycle of hMSCs leading to observed cases of elevated growth rates in labeled cells., Therefore, while a high initial concentration of internalized iron may maintain the long-term detectability of SPIO-labeled hMSCs, this condition may influence cell proliferation in ways that could impact methods of cytotherapeutic monitoring, such as contrast-based in vivo cell counts.
| Human Mesenchymal Stem Cell Proliferation, Differentiation, and Survival Is Minimally Effected by Low Concentrations of Superparamagnetic Iron Oxide|| |
The influence of SPIO labeling on hMSC proliferation and multipotential is vital for selecting the dosage and scheduling of iron labeling for hMSC phenotypes and their functional characteristics. In the study by Rosenberg et al., the hMSC proliferation displayed similar growth patterns as nonlabeled control cells, with no statistical significance found between the various dosages of iron for each time point, signifying insignificant long-term effects of SPIO labeling on hMSC proliferation for lengthy culture duration. Kim et al. and Arbab et al. have reported negligible effects of SPIO labeling in the presence and absence of CPP on hMSC proliferation with an SPIO concentration approximately 12.5-50µg Fe/mL., When a colony-forming unit fibroblast (CFU-F) assay was also conducted following the 14 times point, there was also no statistical significance in CFU-F values, implying a marginal effect of SPIO labeling for hMSC progenicity. These results were additionally verified by the real-time polymerase chain reaction results that exhibited similar expression of Oct-4 and Rex-1. Balakumaran et al. also showed minimal effects of SPIO labeling on hMSC stemness using in vitro and in vivo analyses. There are many past studies that have evaluated these surface markers via flow cytometry for internalized SPIO levels at higher levels than introduced by Rosenberg et al., generally through the administration of nonspecific and specific CPP.,,, Comprehensively, these investigations have found no variations in positive surface markers related to MSCs and only minute alterations of negative markers (e.g., CD45), which can be affected by extended culture periods independently.
Rosenberg et al. showed that labeled hMSCs demonstrate distinctive ALP expression, with a peak at 14 days followed by a decrease from 14 to 21 days. Chen et al. recorded decreased ALP expression by hMSCs labeled with SPIO in a dose-dependent manner while Lee et al. demonstrated analogous in ALP expression following 7 days in osteogenic induction media., ALP expression readies hMSCs for osteogenic differentiation; however, its sole expression is not adequate to conclude the degree of osteogenic differentiation. It is of note that calcification of the SPIO-labeled hMSCs is effected by SPIO labeling at 21 days though statistical insignificance was found between the groups at 14 days. Previous investigations have demonstrated minimal influence of SPIO labeling on calcification, but the induction for these studies was often <2 weeks., The outcome of the current study implies that SPIO labeling has minimal effects on hMSC osteogenic commitment; it does, however, advance calcification following long-term exposure to osteoinductive cues. Further studies to explore the exact mechanism are needed because calcification is a primary concern in stem cell therapy for ischemic cardiovascular and cerebral diseases.
In Rosenberg et al.'s study, lactate dehydrogenase (LDH) was introduced in vitro via SPIO-labeled hMSCs under serum and oxygen depletion that specifies a quantitative measurement for hMSC survival during a simulated in vivo setting. Serum removal had negligible effects on hMSC survival, measured by LDH discharge during the first 24 h, followed by a surge at 36 h. Of note, the combination of low-serum and low-oxygen conditions results in a considerable uptick in LDH release and higher SPIO concentrations representing the highest LDH levels at the 24 h period. The definite mechanism of SPIO dosage-dependent for in vitro ischemic circumstances has yet to be defined for hMSCs. Yet, Soenen et al. demonstrated that stem-like neuroprogenitor cells and escalated SPIO concentrations transfected with external agents, also that internalized dextran-coated SPIOs exhibited an instant and beneficial effect on ROS levels while exhibiting elevated transferrin receptor-1 expression. An ischemic-hypoxic condition would be likely to disturb natural ROS levels, and with the possible effects of internalized SPIOs, labeled hMSCs could be jeopardized when transplanted into the environment. With translation to the clinic in mind for ischemic therapies, further investigations are warranted to assess any possible internal contrasting agent under ischemic-hypoxic influences.
| Magnetic Resonance Imaging Detection of Transplanted Superparamagnetic Iron Oxide-Labeled Human Mesenchymal Stem Cells Appears Highly Effective|| |
Using rhodamine-conjugated SPIOs for labeling of hMSCs exhibits that particles are found in the perinuclear region, most likely internalized within endosomes or lysosomes, as previously shown. In addition, the covalent bonding, of carboxyflourescein succinimidyl ester (CFSE) treated hMSCs, within the cytoplasm allows for it to remain within the cells for long periods of time. Co-localization of the CFSE and rhodamine signals was evident within the stroke-induced hemisphere and was 2.7 more prevalent in the affected hemisphere. However, nuclei not linked to CFSE will also display rhodamine coloration, signaling the release of SPIOs, which is likely a consequence of hMSC death resulting in endogenous microglia/macrophage uptake of SPIOs in vivo. hMSCs were also shown to dispel intracellular iron within 7 days of transplantation, likely a result of asymmetric cell division while the transplanted cells replicated while migrating. As previously stated, hMSCs do not proliferate in the brain for 5–10 days in vivo. Therefore, the fading MRI contrast and dispelling of intracellular iron are possibly connected to cell death rather than through proliferation of hMSCs. IA injection provides a more unabated pathway to the ischemic lesion in the brain in comparison to intravenous injection, in which cells can be taken by other systemic organs., Walczak et al. observed extreme inconsistency in cell transplantation intended for the brain using a similar protocol with SPIO-labeled hMSCs. This indicated that the current transplantation method has only moderate to low efficiency. Yet, it should be noted that Walczak et al. utilized PLL to encourage SPIO uptake which should augment signal voids visible on the MRI.
| Conclusion|| |
The abbreviated incubation period and minimal SPIO exposure dose utilized in Rosenberg et al.'s investigation was significant for recognition in agarose tissue imitating phantoms for a 2-week period with minimal effects on differentiation and proliferation, excluding the osteogenic cues. However, once the SPIO-labeled hMSCs were introduced to a hypoxic and ischemic environment, there was a significant reduction in viability in comparison to the unlabeled hMSCs. These discoveries need to be considered when using hMSCs in ischemic animal models. Further research must be directed at developing methods to precondition hMSCs to assess the mechanism of cellular function and improve the viability of cell transplantations into ischemic regions.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Tang Y, Yasuhara T, Hara K, Matsukawa N, Maki M, Yu G, et al.
Transplantation of bone marrow-derived stem cells: A promising therapy for stroke. Cell Transplant 2007;16:159-69.
Kim YJ, Park HJ, Lee G, Bang OY, Ahn YH, Joe E, et al.
Neuroprotective effects of human mesenchymal stem cells on dopaminergic neurons through anti-inflammatory action. Glia 2009;57:13-23.
Toyama K, Honmou O, Harada K, Suzuki J, Houkin K, Hamada H, et al.
Therapeutic benefits of angiogenetic gene-modified human mesenchymal stem cells after cerebral ischemia. Exp Neurol 2009;216:47-55.
Ohtaki H, Ylostalo JH, Foraker JE, Robinson AP, Reger RL, Shioda S, et al.
Stem/progenitor cells from bone marrow decrease neuronal death in global ischemia by modulation of inflammatory/immune responses. Proc Natl Acad Sci U S A 2008;105:14638-43.
Onda T, Honmou O, Harada K, Houkin K, Hamada H, Kocsis JD. Therapeutic benefits by human mesenchymal stem cells (hMSCs) and Ang-1 gene-modified hMSCs after cerebral ischemia. J Cereb Blood Flow Metab 2008;28:329-40.
Horita Y, Honmou O, Harada K, Houkin K, Hamada H, Kocsis JD. Intravenous administration of glial cell line-derived neurotrophic factor gene-modified human mesenchymal stem cells protects against injury in a cerebral ischemia model in the adult rat. J Neurosci Res 2006;84:1495-504.
Zietlow R, Lane EL, Dunnett SB, Rosser AE. Human stem cells for CNS repair. Cell Tissue Res 2008;331:301-22.
Vercelli A, Mereuta OM, Garbossa D, Muraca G, Mareschi K, Rustichelli D, et al.
Human mesenchymal stem cell transplantation extends survival, improves motor performance and decreases neuroinflammation in mouse model of amyotrophic lateral sclerosis. Neurobiol Dis 2008;31:395-405.
Corti S, Locatelli F, Donadoni C, Guglieri M, Papadimitriou D, Strazzer S, et al.
Wild-type bone marrow cells ameliorate the phenotype of SOD1-G93A ALS mice and contribute to CNS, heart and skeletal muscle tissues. Brain 2004;127(Pt 11):2518-32.
Mazzini L, Mareschi K, Ferrero I, Vassallo E, Oliveri G, Boccaletti R, et al.
Autologous mesenchymal stem cells: Clinical applications in amyotrophic lateral sclerosis. Neurol Res 2006;28:523-6.
Caplan AI. Adult mesenchymal stem cells for tissue engineering versus regenerative medicine. J Cell Physiol 2007;213:341-7.
Kern S, Eichler H, Stoeve J, Klüter H, Bieback K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells 2006;24:1294-301.
Bernardo ME, Zaffaroni N, Novara F, Cometa AM, Avanzini MA, Moretta A, et al.
Human bone marrow derived mesenchymal stem cells do not undergo transformation after long-term in vitro
culture and do not exhibit telomere maintenance mechanisms. Cancer Res 2007;67:9142-9.
Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al.
Multilineage potential of adult human mesenchymal stem cells. Science 1999;284:143-7.
Friedenstein AJ, Chailakhjan RK, Lalykina KS. The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet 1970;3:393-403.
Pavlichenko N, Sokolova I, Vijde S, Shvedova E, Alexandrov G, Krouglyakov P, et al.
Mesenchymal stem cells transplantation could be beneficial for treatment of experimental ischemic stroke in rats. Brain Res 2008;1233:203-13.
Caplan AI. Why are MSCs therapeutic? New data: New insight. J Pathol 2009;217:318-24.
Akiyama Y, Radtke C, Honmou O, Kocsis JD. Remyelination of the spinal cord following intravenous delivery of bone marrow cells. Glia 2002;39:229-36.
Omori Y, Honmou O, Harada K, Suzuki J, Houkin K, Kocsis JD. Optimization of a therapeutic protocol for intravenous injection of human mesenchymal stem cells after cerebral ischemia in adult rats. Brain Res 2008;1236:30-8.
Liu H, Honmou O, Harada K, Nakamura K, Houkin K, Hamada H, et al.
Neuroprotection by PlGF gene-modified human mesenchymal stem cells after cerebral ischaemia. Brain 2006;129(Pt 10):2734-45.
Nomura T, Honmou O, Harada K, Houkin K, Hamada H, Kocsis JD. IV infusion of brain-derived neurotrophic factor gene-modified human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat. Neuroscience 2005;136:161-9.
Honma T, Honmou O, Iihoshi S, Harada K, Houkin K, Hamada H, et al.
Intravenous infusion of immortalized human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat. Exp Neurol 2006;199:56-66.
Iihoshi S, Honmou O, Houkin K, Hashi K, Kocsis JD. A therapeutic window for intravenous administration of autologous bone marrow after cerebral ischemia in adult rats. Brain Res 2004;1007:1-9.
Li Y, Chen J, Chen XG, Wang L, Gautam SC, Xu YX, et al.
Human marrow stromal cell therapy for stroke in rat: Neurotrophins and functional recovery. Neurology 2002;59:514-23.
Delcroix GJ, Jacquart M, Lemaire L, Sindji L, Franconi F, Le Jeune JJ, et al.
Mesenchymal and neural stem cells labeled with HEDP-coated SPIO nanoparticles: In vitro
characterization and migration potential in rat brain. Brain Res 2009;1255:18-31.
Chen J, Li Y, Wang L, Lu M, Zhang X, Chopp M. Therapeutic benefit of intracerebral transplantation of bone marrow stromal cells after cerebral ischemia in rats. J Neurol Sci 2001;189:49-57.
Hsiao JK, Tai MF, Chu HH, Chen ST, Li H, Lai DM, et al
. Magnetic nanoparticle labeling of mesenchymal stem cells without transfection agent: Cellular behavior and capability of detection with clinical 1.5 T magnetic resonance at the single cell level. Magn Reson Med 2007;58:717-24.
Ko IK, Song HT, Cho EJ, Lee ES, Huh YM, Suh JS.In vivo
MR imaging of tissue-engineered human mesenchymal stem cells transplanted to mouse: A preliminary study. Ann Biomed Eng 2007;35:101-8.
Kraitchman DL, Bulte JW. Imaging of stem cells using MRI. Basic Res Cardiol 2008;103:105-13.
Bulte JW, Douglas T, Witwer B, Zhang SC, Strable E, Lewis BK, et al.
Magnetodendrimers allow endosomal magnetic labeling and in vivo
tracking of stem cells. Nat Biotechnol 2001;19:1141-7.
Muja N, Bulte JW. Magnetic resonance imaging of cells in experimental disease models. Prog Nucl Magn Reson Spectrosc 2009;55:61-77.
Bulte JW, Zhang S, van Gelderen P, Herynek V, Jordan EK, Duncan ID, et al.
Neurotransplantation of magnetically labeled oligodendrocyte progenitors: Magnetic resonance tracking of cell migration and myelination. Proc Natl Acad Sci U S A 1999;96:15256-61.
Bulte JW, Kraitchman DL. Iron oxide MR contrast agents for molecular and cellular imaging. NMR Biomed 2004;17:484-99.
Walczak P, Kedziorek DA, Gilad AA, Barnett BP, Bulte JW. Applicability and limitations of MR tracking of neural stem cells with asymmetric cell division and rapid turnover: The case of the shiverer dysmyelinated mouse brain. Magn Reson Med 2007;58:261-9.
Kim HS, Oh SY, Joo HJ, Son KR, Song IC, Moon WK. The effects of clinically used MRI contrast agents on the biological properties of human mesenchymal stem cells. NMR Biomed 2010;23:514-22.
Kostura L, Kraitchman DL, Mackay AM, Pittenger MF, Bulte JW. Feridex labeling of mesenchymal stem cells inhibits chondrogenesis but not adipogenesis or osteogenesis. NMR Biomed 2004;17:513-7.
Farrell E, Wielopolski P, Pavljasevic P, van Tiel S, Jahr H, Verhaar J, et al.
Effects of iron oxide incorporation for long term cell tracking on MSC differentiation in vitro
and in vivo
. Biochem Biophys Res Commun 2008;369:1076-81.
Chen YC, Hsiao JK, Liu HM, Lai IY, Yao M, Hsu SC, et al.
The inhibitory effect of superparamagnetic iron oxide nanoparticle (Ferucarbotran) on osteogenic differentiation and its signaling mechanism in human mesenchymal stem cells. Toxicol Appl Pharmacol 2010;245:272-9.
Rosenberg JT, Sellgren KL, Sachi-Kocher A, Bejarano FC, Baird MA, Davidson MW, et al
. Magnetic resonance contrast and biological effects of intracellular superparamagnetic iron oxides on human mesenchymal stem cells with long-term culture and hypoxic exposure. Cytotherapy2013;15:307-22.
Bulte JW. Magnetic nanoparticles as markers for cellular MR imaging. J Magn Magn Mater 2005;289:423.
Weissleder R, Stark DD, Engelstad BL, Bacon BR, Compton CC, White DL, et al.
Superparamagnetic iron oxide: Pharmacokinetics and toxicity. AJR Am J Roentgenol 1989;152:167-73.
Yang C, Tai M, Chen S, Wang Y, Chen Y, Hsiao J. Labeling of human mesenchymal stem cell: Comparison between paramagnetic and superparamagnetic agents. J Appl Phys 2009;105:07B314-1-07B314-3.
Omidkhoda A, Mozdarani H, Movasaghpoor A, Fatholah AA. Study of apoptosis in labeled mesenchymal stem cells with superparamagnetic iron oxide using neutral comet assay. ToxicolIn Vitro
Lee JH, Jung MJ, Hwang YH, Lee YJ, Lee S, Lee DY, et al.
Heparin-coated superparamagnetic iron oxide for in vivo
MR imaging of human MSCs. Biomaterials 2012;33:4861-71.
Komatsu K, Honmou O, Suzuki J, Houkin K, Hamada H, Kocsis JD. Therapeutic time window of mesenchymal stem cells derived from bone marrow after cerebral ischemia. Brain Res 2010;1334:84-92.
Bonfield TL, Koloze M, Lennon DP, Zuchowski B, Yang SE, Caplan AI. Human mesenchymal stem cells suppress chronic airway inflammation in the murine ovalbumin asthma model. Am J Physiol Lung Cell Mol Physiol 2010;299:L760-70.
Bonfield TL, Nolan Koloze MT, Lennon DP, Caplan AI. Defining human mesenchymal stem cell efficacy in vivo
. J Inflamm (Lond) 2010;7:51.
Heyn C, Bowen CV, Rutt BK, Foster PJ. Detection threshold of single SPIO-labeled cells with FIESTA. Magn Reson Med 2005;53:312-20.
Bowen CV, Zhang X, Saab G, Gareau PJ, Rutt BK. Application of the static dephasing regime theory to superparamagnetic iron-oxide loaded cells. Magn Reson Med 2002;48:52-61.
Amstad E, Zurcher S, Mashaghi A, Wong JY, Textor M, Reimhult E. Surface functionalization of single superparamagnetic iron oxide nanoparticles for targeted magnetic resonance imaging. Small 2009;5:1334-42.
Weissleder R, Lee AS, Khaw BA, Shen T, Brady TJ. Antimyosin-labeled monocrystalline iron oxide allows detection of myocardial infarct: MR antibody imaging. Radiology 1992;182:381-5.
Weissleder R, Lee AS, Fischman AJ, Reimer P, Shen T, Wilkinson R, et al.
Polyclonal human immunoglobulin G labeled with polymeric iron oxide: Antibody MR imaging. Radiology 1991;181:245-9.
Dodd SJ, Williams M, Suhan JP, Williams DS, Koretsky AP, Ho C. Detection of single mammalian cells by high-resolution magnetic resonance imaging. Biophys J 1999;76 (1 Pt 1):103-9.
Bulte JW, Hoekstra Y, Kamman RL, Magin RL, Webb AG, Briggs RW, et al.
Specific MR imaging of human lymphocytes by monoclonal antibody-guided dextran-magnetite particles. Magn Reson Med 1992;25:148-57.
Frank JA, Miller BR, Arbab AS, Zywicke HA, Jordan EK, Lewis BK, et al.
Clinically applicable labeling of mammalian and stem cells by combining superparamagnetic iron oxides and transfection agents. Radiology 2003;228:480-7.
Bulte JW, Ma LD, Magin RL, Kamman RL, Hulstaert CE, Go KG, et al.
Selective MR imaging of labeled human peripheral blood mononuclear cells by liposome mediated incorporation of dextran-magnetite particles. Magn Reson Med 1993;29:32-7.
Bulte JW, Laughlin PG, Jordan EK, Tran VA, Vymazal J, Frank JA. Tagging of T cells with superparamagnetic iron oxide: Uptake kinetics and relaxometry. Acad Radiol 1996;3 Suppl 2:S301-3.
Yan GP, Robinsonad L, Hogg P. Magnetic resonance imaging contrast agents: Overview and perspectives. Radiography 2006;13:1-15.
Soenen SJ, Himmelreich U, Nuytten N, De Cuyper M. Cytotoxic effects of iron oxide nanoparticles and implications for safety in cell labelling. Biomaterials 2011;32:195-205.
Huang DM, Hsiao JK, Chen YC, Chien LY, Yao M, Chen YK, et al.
The promotion of human mesenchymal stem cell proliferation by superparamagnetic iron oxide nanoparticles. Biomaterials 2009;30:3645-51.
Arbab AS, Bashaw LA, Miller BR, Jordan EK, Lewis BK, Kalish H, et al.
Characterization of biophysical and metabolic properties of cells labeled with superparamagnetic iron oxide nanoparticles and transfection agent for cellular MR imaging. Radiology 2003;229:838-46.
Balakumaran A, Pawelczyk E, Ren J, Sworder B, Chaudhry A, Sabatino M, et al.
Superparamagnetic iron oxide nanoparticles labeling of bone marrow stromal (mesenchymal) cells does not affect their “stemness”. PLoS One 2010;5:e11462.
Crabbe A, Vandeputte C, Dresselaers T, Sacido AA, Verdugo JM, Eyckmans J, et al.
Effects of MRI contrast agents on the stem cell phenotype. Cell Transplant 2010;19:919-36.
Reddy AM, Kwak BK, Shim HJ, Ahn C, Lee HS, Suh YJ, et al. In vivo
tracking of mesenchymal stem cells labeled with a novel chitosan-coated superparamagnetic iron oxide nanoparticles using 3.0T MRI. J Korean Med Sci 2010;25:211-9.
Kim J, Ma T. Perfusion regulation of hMSC microenvironment and osteogenic differentiation in 3D scaffold. Biotechnol Bioeng 2012;109:252-61.
Yoon YS, Park JS, Tkebuchava T, Luedeman C, Losordo DW. Unexpected severe calcification after transplantation of bone marrow cells in acute myocardial infarction. Circulation 2004;109:3154-7.
Hauger O, Frost EE, van Heeswijk R, Deminière C, Xue R, Delmas Y, et al.
MR evaluation of the glomerular homing of magnetically labeled mesenchymal stem cells in a rat model of nephropathy. Radiology 2006;238:200-10.
Kraitchman DL, Tatsumi M, Gilson WD, Ishimori T, Kedziorek D, Walczak P, et al.
Dynamic imaging of allogeneic mesenchymal stem cells trafficking to myocardial infarction. Circulation 2005;112:1451-61.
Walczak P, Zhang J, Gilad AA, Kedziorek DA, Ruiz-Cabello J, Young RG, et al.
Dual-modality monitoring of targeted intraarterial delivery of mesenchymal stem cells after transient ischemia. Stroke 2008;39:1569-74.
|This article has been cited by|
||Force-Mediated Endocytosis of Iron Oxide Nanoparticles for Magnetic Targeting of Stem Cells
| ||Linlin Zhang, Samira Hajebrahimi, Sheng Tong, Xueqin Gao, Haizi Cheng, Qingbo Zhang, Daniel T. Hinojosa, Kaiyi Jiang, Lin Hong, Johnny Huard, Gang Bao |
| ||ACS Applied Materials & Interfaces. 2023; |
|[Pubmed] | [DOI]|
||Nuclear magnetic resonance footprint of Wharton Jelly mesenchymal stem cells death mechanisms and distinctive in-cell biophysical properties in vitro
| ||Artur T. Krzyzak, Iwona Habina-Skrzyniarz, Weronika Mazur, Maciej Sulkowski, Marta Kot, Marcin Majka |
| ||Journal of Cellular and Molecular Medicine. 2022; |
|[Pubmed] | [DOI]|
||Vitality-Enhanced Dual-Modal Tracking System Reveals the Dynamic Fate of Mesenchymal Stem Cells for Stroke Therapy
| ||Jianpei Xu, Yuwen Zhang, Yipu Liu, Yang You, Fengan Li, Yu Chen, Laozhi Xie, Shiqiang Tong, Songlei Zhou, Kaifan Liang, Yukun Huang, Gan Jiang, Qingxiang Song, Ni Mei, Fenfen Ma, Xiaoling Gao, He Wang, Jun Chen |
| ||Small. 2022; : 2203431 |
|[Pubmed] | [DOI]|
||Iron Oxide Nanoparticles in Mesenchymal Stem Cell Detection and Therapy
| ||Kosha J. Mehta |
| ||Stem Cell Reviews and Reports. 2022; |
|[Pubmed] | [DOI]|
||The effects of intravenous infusion of autologous mesenchymal stromal cells in patients with subacute middle cerebral artery infarct: a phase 2 randomized controlled trial on safety, tolerability and efficacy
| ||Zhe Kang Law,Hui Jan Tan,Sze Piaw Chin,Chee Yin Wong,Wan Nur Nafisah Wan Yahya,Ahmad Sobri Muda,Rozman Zakaria,Mohd Izhar Ariff,Nor Azimah Ismail,Soon Keng Cheong,S. Fadilah S Abdul Wahid,Norlinah Mohamed Ibrahim |
| ||Cytotherapy. 2021; |
|[Pubmed] | [DOI]|
||Iron Oxide Nanoparticles as Theranostic Agents in Cancer Immunotherapy
| ||Rossella Canese,Federica Vurro,Pasquina Marzola |
| ||Nanomaterials. 2021; 11(8): 1950 |
|[Pubmed] | [DOI]|
||Application of Nanotechnology in Stem-Cell-Based Therapy of Neurodegenerative Diseases
| ||Shima Masoudi Asil,Jyoti Ahlawat,Gileydis Guillama Barroso,Mahesh Narayan |
| ||Applied Sciences. 2020; 10(14): 4852 |
|[Pubmed] | [DOI]|
||Multiparametric classification of sub-acute ischemic stroke recovery with ultrafast diffusion,
Na, and MPIO-labeled stem cell MRI at 21.1 T
| ||Avigdor Leftin,Jens T. Rosenberg,Xuegang Yuan,Teng Ma,Samuel C. Grant,Lucio Frydman |
| ||NMR in Biomedicine. 2019; |
|[Pubmed] | [DOI]|
||Aggregation of human mesenchymal stem cells enhances survival and efficacy in stroke treatment
| ||Xuegang Yuan,Jens T. Rosenberg,Yijun Liu,Samuel C. Grant,Teng Ma |
| ||Cytotherapy. 2019; |
|[Pubmed] | [DOI]|