Effects of magnetic nanoparticle‐incorporated human bone marrow–derived mesenchymal stem cells exposed to pulsed electromagnetic fields on injured rat spinal cord

Jung

International Journal of Molecular Medicine

et al. 2014

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Human bone marrow-derived mesenchymal stem cells (hBM-MSCs) are widely used in a number of cell therapies and have osteogenic differentiation capacity. Exposure to electromagnetic fields (EMFs) increases the osteogenic differentiation of hBM-MSCs. Nanomagnetic particles (MPs) also promote the differentiation potential of stem cells. In the present study, we investigated the effects of EMFs and MPs on the osteogenic differentiation of hBM-MSCs. hBM-MSCs were treated with 50 µg/ml of Fe3O4 MPs or exposed to a frequency of 45 Hz and an intensity of 1 mT EMF twice every 8 h per day for 7 days. MP incorporation, EMF exposure and MP incorporation with exposure to EMFs did not induce cytotoxic effects. A strong expression of osteogenic markers (osteocalcin, osteopontin and osteonectin) and von Kossa staining intensity was observed in the cells treated with MPs, the cells exposed to EMFs and in the cells treated with MPs and exposed to EMFs compared with the control group, as shown by immunohistochemical staining. Quantitative RT-PCR revealed that the mRNA expression levels of osteoblast markers [osteocalcin, osteopontin, osteonectin, collagen Ⅰ, collagen Ⅲ, bone morphogenetic protein 2 (BMP-2), bone sialoprotein (BSP) and runt-related transcription factor 2 (runx-2)] were markedly increased in the cells treated with MPs and exposed to EMFs. Furthermore, the mRNA expression of calcium channels (CACNA1C, CACNA1E, CACNA1G and CACNA1I) was activated during osteogenic differentiation. The expression levels of osteogenesis-related proteins (BSP, BMP-2, osteopontin and osteonectin) and phosphorylated extracellular signal-regulated kinase (p-ERK) were increased in the cells treated with MPs, those exposed to EMFs and in the cells treated with MPs and exposed to EMFs compared with the control group, as shown by western blot analysis. Fluorescence-activated cell sorting (FACS) analysis was performed for the hBM-MSC markers, CD73, CD90 and CD105. The expression levels of hBM-MSC surface antigens were decreased in the cells treated with MPs, those exposed to EMFs and in the cells treated with MPs and exposed to EMFs compared with the control group. The cell numbers were determined to be approximately 3.4 x 10(5) cells in the control group, 3.7 x 10(5) cells in the MP-treated group, 3.1 x 10(5) cells in the group exposed to EMFs and 3.9 x 10(5) cells in the group treated with MPs and exposed to EMFs. The cell mitochondrial activity among the 4 experimental groups was similar. The hBM-MSCs treated with MPs and exposed to EMFs showed an increase in alkaline phosphatase (ALP) activity. Taken together, these results suggest that the treatment of hBM-MSCs with MPs or exposure to EMFs increases osteogenic differentiation, and that treatment with MPs in conjunction with EMF exposure is more effective in increasing osteogenic differentiation.

Section: Preparation and Characterization Of Fe 3 O 4 Mps Waterdispementioning

confidence: 99%

Electromagnetic fields and nanomagnetic particles increase the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells

Jung

International Journal of Molecular Medicine

et al. 2014

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Mesenchymal Stem Cells - Isolation, Characterization and Applications

“…A combinatorial approach has been agreed upon for effective treatment of spinal cord injury [192][193][194][195][196][197][198][199][200][201][202][203][204][205][206][207][208].…”

Section: Supplying Neurotrophic Factors and Accessory Cellsmentioning

confidence: 99%

“…Magnetic targeting of neurotrophin-3 gene-transfected bone marrow mesenchymal stem cells via lumbar puncture has enhanced their delivery to the site of injury and has significantly improved functional recovery and nerve regeneration compared to transplanting neurotrophin-3 gene-transfected bone marrow mesenchymal stem cells without magnetic targeting system [195,196]. Pulsed electromagnetic field exposure near the injured site and for 8 hours per day over 4 weeks has been suggested as a suitable protocol for directing the cells to the site of injury [197]. Electro-acupuncture has promoted the survival and differentiation of transplanted bone marrow mesenchymal stem cells pre-induced with neurotrophin-3 and retinoic acid in gelatin sponge scaffold after rat spinal cord transection [53,198].…”

Section: Supplying Neurotrophic Factors and Accessory Cellsmentioning

confidence: 99%

“…Controlling surface tension as well as hydrophobic and hydrophilic properties of the conduit lumen and the microspheres may help us fulfill the three aims described previously. One method to achieve the latter aim is using magnetic nanoparticle-incorporated human bone marrow-derived mesenchymal stem cells exposed to pulsed electromagnetic fields [190,191,197] (Figure 2).…”

Section: Establishing a Continuous Drug And Cell Delivery Systemmentioning

confidence: 99%

See 1 more Smart Citation

Prerequisites for Mesenchymal Stem Cell Transplantation in Spinal Cord Injury

Amr¹

2017

We have aimed at distinguishing obligatory prerequisites for mesenchymal stem cell transplantation in spinal cord injury from those prerequisites which are unnecessary or are prerequisites that have to be further investigated. Obligatory prerequisites include the following. First, the site of injury is extensively gliotic, constituting an unsuitable medium for stem cell transplantation. It has to be dissolved by neurolyzing agents, chondroitinase ABC as an example. Second, stem cells need a suitable biomaterial scaffold for their proper integration. Third, the biomaterial scaffold necessitates a tissue filler harboring stem cells, other cells and neurotrophic factors in a combinatorial approach. Fourth, the efficiency of mesenchymal stem cells themselves has to be increased (by reducing oxidative stress-induced apoptosis, by hypoxic preconditioning, by modulating the extracellular matrix and by other measures). Prerequisites that have to be further investigated include the ideal source, mode, quantity, time point and number of injections of mesenchymal stem cells; which growth factors and cells to be used in the combinatorial approach; transforming mesenchymal stem cells into motor neuron-like cells or Schwann cells; increasing the homing effect of stem cells and how to establish a continuous drug and cell delivery system.

“…Extremely low frequency magnetic field (ELF-MF) has been reported to improve the quality of life after SCI by significantly increasing locomotor recovery, [32][33][34][35] better autonomic control of urinary bladder, improvement in pain status 36 and gastrointestinal (GI) motility. [37][38][39][40] In addition, there are reports of facilitation of neuroregenerative processes after nerve injury.…”

Section: Introductionmentioning

confidence: 99%

Abnormal feeding behaviour in spinalised rats is mediated by hypothalamus: Restorative effect of exposure to extremely low frequency magnetic field

2016