Umbilical cord mesenchymal stem cells labeled with multimodal iron oxide nanoparticles with fluorescent and magnetic properties: application for in vivo cell tracking

Sibov, Tatiana Taís; Pavon, Lorena Favaro; Miyaki, Liza Aya Mabuchi; Mamani, Javier Bustamante; Nucci, Leopoldo Penteado; Alvarim, Larissa T; Silveira, Paulo Henrique; Marti, Luciana Cavalheiro; Gamarra, Lionel Fernel

doi:10.2147/ijn.s53299

Cited by 25 publications

(20 citation statements)

References 44 publications

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“…Our group provided evidence, in previous studies, that a low nanoparticle concentration in the labeling process was enough to detect stem cell migration homing and tracking. Additionally, nanoparticle sizes of between 35 and 200 nm used in our previous studies showed magnetic characteristics adequate for detection by MRI [65][66][67]. This review corroborates the nanoparticle size findings among the selected studies (60 to 180 nm).…”

Section: Discussionsupporting

confidence: 85%

Noninvasive Tracking of Hematopoietic Stem Cells in a Bone Marrow Transplant Model

Oliveira

Nucci

Filgueiras

et al. 2020

Cells

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The hematopoietic stem cell engraftment depends on adequate cell numbers, their homing, and the subsequent short and long-term engraftment of these cells in the niche. We performed a systematic review of the methods employed to track hematopoietic reconstitution using molecular imaging. We searched articles indexed, published prior to January 2020, in PubMed, Cochrane, and Scopus with the following keyword sequences: (Hematopoietic Stem Cell OR Hematopoietic Progenitor Cell) AND (Tracking OR Homing) AND (Transplantation). Of 2191 articles identified, only 21 articles were included in this review, after screening and eligibility assessment. The cell source was in the majority of bone marrow from mice (43%), followed by the umbilical cord from humans (33%). The labeling agent had the follow distribution between the selected studies: 14% nanoparticle, 29% radioisotope, 19% fluorophore, 19% luciferase, and 19% animal transgenic. The type of graft used in the studies was 57% allogeneic, 38% xenogeneic, and 5% autologous, being the HSC receptor: 57% mice, 9% rat, 19% fish, 5% for dog, porcine and salamander. The imaging technique used in the HSC tracking had the following distribution between studies: Positron emission tomography/single-photon emission computed tomography 29%, bioluminescence 33%, fluorescence 19%, magnetic resonance imaging 14%, and near-infrared fluorescence imaging 5%. The efficiency of the graft was evaluated in 61% of the selected studies, and before one month of implantation, the cell renewal was very low (less than 20%), but after three months, the efficiency was more than 50%, mainly in the allogeneic graft. In conclusion, our review showed an increase in using noninvasive imaging techniques in HSC tracking using the bone marrow transplant model. However, successful transplantation depends on the formation of engraftment, and the functionality of cells after the graft, aspects that are poorly explored and that have high relevance for clinical analysis.

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Section: Discussionsupporting

confidence: 85%

Noninvasive Tracking of Hematopoietic Stem Cells in a Bone Marrow Transplant Model

Oliveira

Nucci

Filgueiras

et al. 2020

Cells

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“…MSCs can be isolated from the umbilical cord (UC) lining, subendothelial layer, perivascular zone, and the Wharton’s Jelly (WJ) (the gelatinous matrix in the umbilical cord that provides insulation and protection of the vein and arteries of the umbilical cord) [5] (Figure 1). The MSCs found in these regions of the hUC are multipotent and can differentiate into adipogenic, osteogenic, chondrogenic, and neuronal cells [6].…”

Section: Introductionmentioning

confidence: 99%

Discarded Wharton jelly of the human umbilical cord: a viable source for mesenchymal stromal cells

Watson¹,

Divers²,

Kedar

et al. 2015

Cytotherapy

112

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Mesenchymal stem cells (MSCs) are multipotent cells that have the capability of differentiating into adipogenic, osteogenic, chondrogenic, and neural cells. With these multiple capabilities, MSCs have been highly regarded as effective transplantable cell source for regenerative medicine. A large bank of these cells can be found in several regions of the human umbilical cord (hUC) including the umbilical cord lining, the subendothelial layer, the perivascular zone, and most importantly in Wharton’s jelly (WJ). These cells, all umbilical cord-derived MSCs, are very durable, have large loading capacities, and are considered ethical to harvest because the umbilical cord is often considered a waste. These logistical advantages make WJ as appealing source of stem cells for transplant therapy. In particular, WJ is a predominantly good source of cells because MSCs in WJ (WJ-MSC) are maintained in a very early embryological phase and therefore have retained some of the primitive stemness properties. WJ-MSCs can easily differentiate into a plethora of cell types leading to a variety of applications. In addition, WJ-MSCs are slightly easier to harvest compared to other MSCs (such as bone marrow-derived MSCs). The fascinating stemness properties and therapeutic potential of WJ-MSCs provide great promise in many aspects of regenerative medicine and should be considered for further investigations as safe and effective donor cells for transplantation therapy in many debilitating disorders, which are discussed here. We previously reviewed WJ-MSCs therapeutic potential [1] and now provide an update on their recent preclinical and clinical applications.

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“…Regarding the stability of nanoparticles in the labeling process, previous studies by our group [90][91][92] evaluated SPION stability before labeling in different media and demonstrated that supplementation with 10% fetal bovine serum (FBS) contributed stabilized SPIONs in the culture medium during the labeling process [90,91,93]. This type of strategy was also reported in other studies [54,58,59,85,87], with FBS concentrations ranging from 5% to 20% during the labeling process of granulocytes or leucocytes with SPIONs.…”

Section: Discussionmentioning

confidence: 56%

Methods of Granulocyte Isolation from Human Blood and Labeling with Multimodal Superparamagnetic Iron Oxide Nanoparticles

et al. 2020

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This in vitro study aimed to find the best method of granulocyte isolation for subsequent labeling with multimodal nanoparticles (magnetic and fluorescent properties) to enable detection by optical and magnetic resonance imaging (MRI) techniques. The granulocytes were obtained from venous blood samples from 12 healthy volunteers. To achieve high purity and yield, four different methods of granulocyte isolation were evaluated. The isolated granulocytes were labeled with multimodal superparamagnetic iron oxide nanoparticles (M-SPIONs) coated with dextran, and the iron load was evaluated qualitatively and quantitatively by MRI, near-infrared fluorescence (NIRF) and inductively coupled plasma mass spectrometry (ICP-MS). The best method of granulocyte isolation was Percoll with Ficoll, which showed 95.92% purity and 94% viability. After labeling with M-SPIONs, the granulocytes showed 98.0% purity with a yield of 3.5 × 10 6 cells/mL and more than 98.6% viability. The iron-loading value in the labeled granulocytes, as obtained by MRI, was 6.40 ± 0.18 pg/cell. Similar values were found with the ICP-MS and NIRF imaging techniques. Therefore, our study shows that it is possible to isolate granulocytes with high purity and yield and labeling with M-SPIONs provides a high internalized iron load and low toxicity to cells. Therefore, these M-SPION-labeled granulocytes could be a promising candidate for future use in inflammation/infection detection by optical and MRI techniques.Hard-to-reach or occult inflammation and infection processes are clinically challenging. Their clinical diagnoses involve biochemical and radiological examinations, but these methods can produce false negatives [11][12][13][14][15]. To determine the localization, extent and severity of inflammation, imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) can be performed but have limitations in the early stages of the disease, as they are dependent on morphological changes [16][17][18]. Accurate and early diagnosis of inflammation and infection helps reduce mortality and morbidity and increase drug treatment success [19][20][21].Proinflammatory effects help leukocytes migrate from the blood vessel to the site of injury, due to increased vascular permeability through stimulation by cytokines and interleukins. There is an initial accumulation of granulocytes, mainly neutrophils, in the inflamed area and later of lymphocytes and macrophages [22][23][24]. Granulocytes are the most abundant subset of leukocytes [25] and are produced in the bone marrow, originating from myeloid precursor cells and undergoing a maturing process before they are able to perform their functions, mainly phagocytosis [25,26]. They differ from other cells in that they have granules with proteolytic enzymes that fight microorganisms or other inflammatory agents [25,27]. Granulocytes are considered frontline cells in inflammation and infection processes [28]. In many cases, to detect inflammation/infection, it is necessary to label isolated granulocyte...

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Umbilical cord mesenchymal stem cells labeled with multimodal iron oxide nanoparticles with fluorescent and magnetic properties: application for in vivo cell tracking

Cited by 25 publications

References 44 publications

Noninvasive Tracking of Hematopoietic Stem Cells in a Bone Marrow Transplant Model

Noninvasive Tracking of Hematopoietic Stem Cells in a Bone Marrow Transplant Model

Discarded Wharton jelly of the human umbilical cord: a viable source for mesenchymal stromal cells

Methods of Granulocyte Isolation from Human Blood and Labeling with Multimodal Superparamagnetic Iron Oxide Nanoparticles

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