The safety and efficacy of magnetic targeting using autologous mesenchymal stem cells for cartilage repair

Kamei, Naosuke; Ochi, Mitsuo; Adachi, Nobuo; Ishikawa, Masakazu; Yanada, Shinobu; Levin, Lowell S.; Kamei, Goki; Kobayashi, Takaaki

doi:10.1007/s00167-018-4898-2

Cited by 46 publications

(47 citation statements)

References 41 publications

(48 reference statements)

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“…Summarizing, we established and validated a handy and versatile magnetic bio-technology able to generate on-demand complex 3D cellular architectures in implantable scaffolds. It represents a prototype on an innovative 3D cellular printer based on remote magnetic control, while its validation in vivo should necessarily be tailored to the specific biological situation under investigation 44 . We believe that this technology provides unavailable so far routes and means for the achievement of cell populations and distribution inside the tissue regeneration implants.…”

Section: Discussionmentioning

confidence: 99%

3D Patterning of cells in Magnetic Scaffolds for Tissue Engineering

Goranov

Shelyakova

Santis

et al. 2020

Sci Rep

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A three dimensional magnetic patterning of two cell types was realised in vitro inside an additive manufactured magnetic scaffold, as a conceptual precursor for the vascularised tissue. The realisation of separate arrangements of vascular and osteoprogenitor cells, labelled with biocompatible magnetic nanoparticles, was established on the opposite sides of the scaffold fibres under the effect of nonhomogeneous magnetic gradients and loading magnetic configuration. The magnetisation of the scaffold amplified the guiding effects by an additional trapping of cells due to short range magnetic forces. The mathematical modelling confirmed the strong enhancement of the magnetic gradients and their particular geometrical distribution near the fibres, defining the preferential cell positioning on the micro-scale. The manipulation of cells inside suitably designed magnetic scaffolds represents a unique solution for the assembling of cellular constructs organised in biologically adequate arrangements.Nanotechnology and nanomaterials provide numerous innovative solutions for tissue engineering, aiming at radical reinforcement and renovation of clinical practice. The rapidly growing field of tissue engineering points at the regeneration of damaged tissues, rather than their substitution, and promotes that by implanting templates for tissue regeneration, typically represented by ceramic or polymeric scaffolds 1 . The implantation of bare cell-free scaffolds has serious limitations, especially considering the regular development of the vascular network in the regenerated tissue 2,3 . The most promising solution to this problem is the in vitro pre-loading of scaffolds with cells and/or growth factors before the implantation. The realisation of a correct distribution of cells inside the three-dimensional scaffolds is a key element for the maximally complete regeneration 1,4 . On the other hand, the manipulation and seeding of cells throughout the whole volume of the scaffold is an extremely challenging task and can be partially achieved via technologically sophisticated platforms 5 , barely compatible with routine clinical practice. Moreover, most tissues and organs are composed of various types of cells, preferentially arranged in complex 3D architectures, where they interact with each other and with the organism as a whole 6,7 , complicating further the requisites for a correct pre-loading. A partial solution to this challenging demand consists in the employment of the predominant cell type which defines the main tissue function 8 . This approach is generally suitable for relatively homogeneous tissues, such as cartilage, where tissue development should not be actively supported by other cell types 9 . For other tissues the achievement of efficient vascularisation, cell migration and organisation of the extracellular matrix 10 should be necessarily supported by assembles of different cell types inside the scaffold before implantation 11 .In this paper we propose a new, versatile and easy-to-implement method promoting the three-...

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Section: Discussionmentioning

confidence: 99%

3D Patterning of cells in Magnetic Scaffolds for Tissue Engineering

Goranov

Shelyakova

Santis

et al. 2020

Sci Rep

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“…Mesenchymal stem cell (MSC) therapies have demonstrated efficacy in cartilage repair in both animal studies [3] and human clinical trials [4]. The efficacy of MSC-based therapies, which was previously predicated on the chondrogenic potential of MSC, has been increasingly attributed to the paracrine secretion, particularly exosomes.…”

Section: Introductionmentioning

confidence: 99%

MSC-derived exosomes promote proliferation and inhibit apoptosis of chondrocytes via lncRNA-KLF3-AS1/miR-206/GIT1 axis in osteoarthritis

Liu¹,

Lin²,

Zou³

et al. 2018

Cell Cycle

254

195

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Background: Exosomes secreted by human mesenchymal stem cells (hMSCs) have been shown to promote cartilage regeneration. This study aimed to explore whether exosomal lncRNA-KLF3-AS1 derived from hMSCs can promote chondrocyte proliferation via miR-206/GIT1 axis in osteoarthritis (OA). Methods: hMSCs and MSC-derived exosomes (MSC-exo) were prepared for morphological observation and identification by transmission electron microscopy (TEM) and flow cytometry. IL-1β-induced OA chondrocytes and collagenase-induced mouse OA model were established for the further experiments. Luciferase activity assay was performed to test whether miR-206 could bind to KLF3-AS1 or GIT1. Cell proliferation and apoptosis were evaluated by CCK-8 assay and flow cytometry, respectively. Results: MSC-Exos increased chondrogenic genes Col2a1 (type II collagen alpha 1) and aggrecan, decreased hondrocyte hypertrophy markers MMP-13 (matrix metalloproteinase-13) and Runx2 (runtrelated transcription factor 2) in chondrocytes isolated from OA model mice. Furthermore, MSC-Exos attenuated IL-1β-induced chondrocyte proliferation inhibition and apoptosis induction. Moreover, MSC KLF3-AS1 -Exos (exosomes derived from KLF3-AS1-overexpressing-MSCs) ameliorated IL-1β-induced chondrocyte injury. Results also demonstrated that KLF3-AS1 acted as a competitive endogenous RNA (ceRNA) by sponging miR-206 to facilitate GIT1 expression. In addition, miR-206 overexpression and GIT1 knockdown reversed MSC KLF3-AS1 -Exos-mediated attenuation of chondrocyte injury. Conclusion: Exosomal KLF3-AS1 derived from MSCs involved in MSC-Exos-mediated chondrocyte proliferation induction and chondrocyte apoptosis inhibition via miR-206/GIT1 axis. Abbreviation: G-protein-coupled receptor kinase interacting protein-1 (GIT1) ARTICLE HISTORY

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“…MSCs have been recognized as ideal seed cells for cartilage tissue engineering in treatment of articular cartilage defect and widely used in clinic. 13,14 The chondrogenic differentiation of MSCs was mainly regulated by growth factors. 15 The results of GO analysis suggested that NGF and TGF-β1 exerted the similar mechanism in CC and MF categories.…”

Section: Discussionmentioning

confidence: 99%

Comparative profiling of chondrogenic differentiation of mesenchymal stem cells (MSCs) driven by two different growth factors

Zhan

Cai

Lei

et al. 2019

Cell Biochemistry & Function

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This study aimed to investigate the mechanism of nerve growth factor (NGF) from cobra venom and human transforming growth factor‐β1 (TGF‐β1) on the chondrogenic induction of mesenchymal stem cells (MSCs). NGF and TGF‐β1 were used to induce chondrogenesis of MSCs from rabbits for 7 days. Total RNA was extracted for mRNA sequencing. Differentially expressed genes (DEGs), gene ontology (GO), KEGG pathway enrichment, and PPI network analysis were conducted to screen the specific signalling pathways and target genes. Quantitative real‐time polymerase chain reaction (qRT‐PCR) was performed to further confirm the relative target genes. The results showed that NGF could significantly promote the expression of hyaline cartilage specific genes (collagen type II alpha 1 chain, COL2A1) compared with TGF‐β1. PI3K‐AKT signalling pathway is commonly involved in the chondrogenesis of MSCs induced by NGF and TGF‐β1. However, the expression levels of the genes in the PI3K‐AKT signalling pathway were significantly higher in NGF group than that in the TGF‐β1 group. In the process of chondrogenesis of MSCs induced by NGF and TGF‐β1, integrin (ITGAs) were the targeted hub genes to activate the PI3K‐AKT signalling pathway. NGF could activate more proliferation and differentiation genes in the process of chondrogenesis of MSCs than TGF‐β1. TGF‐β1 promoted angiogenesis by targeting the thrombospondin (THBS1) and THBS2 which might contribute to the osteophyte formation. PI3K‐AKT was the crucial signalling pathway for chondrogenic differentiation. NGF could activate the PI3K‐AKT signalling pathway to a higher level, and NGF had more specificity for promoting expression of specific genes of chondrocyte compared with TGF‐β1. Significance of the study In our study, we compared two different growth factors in promoting cartilage differentiation of MSCs and found some similarities and differences. We revealed that both NGF and TGF‐β1 could activate the PI3K‐AKT signalling pathway (the expression of it in NGF was higher) by targeting the ITGAs in the process of chondrogenesis from MSCs. However, NGF could activate more proliferation and differentiation genes in the process of chondrogenesis of MSCs, whereas TGF‐β1 caused osteophyte formation by activating THBS1 and THBS2. These might be the reason why NGF could promote cartilage differentiation more specifically.

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The safety and efficacy of magnetic targeting using autologous mesenchymal stem cells for cartilage repair

Abstract: IV.

Cited by 46 publications

References 41 publications

3D Patterning of cells in Magnetic Scaffolds for Tissue Engineering

3D Patterning of cells in Magnetic Scaffolds for Tissue Engineering

MSC-derived exosomes promote proliferation and inhibit apoptosis of chondrocytes via lncRNA-KLF3-AS1/miR-206/GIT1 axis in osteoarthritis

Comparative profiling of chondrogenic differentiation of mesenchymal stem cells (MSCs) driven by two different growth factors

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