In VitroEffects of Strontium on Proliferation and Osteoinduction of Human Preadipocytes

Development of tools to be used forin vivobone tissue regeneration focuses on cellular models and differentiation processes. In searching for all the optimal sources, adipose tissue-derived mesenchymal stem cells (hADSCs or preadipocytes) are able to differentiate into osteoblasts with analogous characteristics to bone marrow mesenchymal stem cells, producing alkaline phosphatase (ALP), collagen, osteocalcin, and calcified nodules, mainly composed of hydroxyapatite (HA). The possibility to influence bone differentiation of stem cells encompasses local and systemic methods, including the use of drugs administered systemically. Among the latter, strontium ranelate (SR) represents an interesting compound, acting as an uncoupling factor that stimulates bone formation and inhibits bone resorption. The aim of our study was to evaluate thein vitroeffects of a wide range of strontium (Sr2+) concentrations on proliferation, ALP activity, and mineralization of a novel finite clonal hADSCs cell line, named PA20-h5. Sr2+promoted PA20-h5 cell proliferation while inducing the increase of ALP activity and gene expression as well as HA production duringin vitroosteoinduction. These findings indicate a role for Sr2+in supporting bone regeneration during the process of skeletal repair in general, and, more specifically, when cell therapies are applied.

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Differentiation of mesenchymal stem cells from humans and animals into insulin-producing cells: An overview in vitro induction forms

Current Stem Cell Research & Therapy ◽

10.2174/1574888x16666201229124429 ◽

2020 ◽

Vol 16 ◽

Author(s):

Bruna O. S. Câmara ◽

Bruno M. Bertassoli ◽

Natália M. Ocarino ◽

Rogéria Serakides

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Culture Medium ◽

Adipogenic Differentiation ◽

Medium Composition ◽

Cell Therapies ◽

Insulin Producing Cells ◽

Msc Differentiation

The use of stem cells in cell therapies has shown promising results in the treatment of several diseases, including diabetes mellitus, in both humans and animals. Mesenchymal stem cells (MSCs) can be isolated from various locations, including bone marrow, adipose tissues, synovia, muscles, dental pulp, umbilical cords, and the placenta. In vitro, by manipulating the composition of the culture medium or transfection, MSCs can differentiate into several cell lineages, including insulin-producing cells (IPCs). Unlike osteogenic, chondrogenic, and adipogenic differentiation, for which the culture medium and time are similar between studies, studies involving the induction of MSC differentiation in IPCs differ greatly. This divergence is usually evident in relation to the differentiation technique used, the composition of the culture medium, the cultivation time, which can vary from a few hours to several months, and the number of steps to complete differentiation. However, although there is no “gold standard” differentiation medium composition, most prominent studies mention the use of nicotinamide, exedin-4, ß-mercaptoethanol, fibroblast growth factor b (FGFb), and glucose in the culture medium to promote the differentiation of MSCs into IPCs. Therefore, the purpose of this review is to investigate the stages of MSC differentiation into IPCs both in vivo and in vitro, as well as address differentiation techniques and molecular actions and mechanisms by which some substances, such as nicotinamide, exedin-4, ßmercaptoethanol, FGFb, and glucose, participate in the differentiation process.

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Recombinant human BMP-2 accelerates the migration of bone marrow mesenchymal stem cells via the CDC42/PAK1/LIMK1 pathway in vitro and in vivo

Biomaterials Science ◽

10.1039/c8bm00846a ◽

2019 ◽

Vol 7 (1) ◽

pp. 362-372 ◽

Cited By ~ 6

Author(s):

Shuhao Liu ◽

Yang Liu ◽

Libo Jiang ◽

Zheng Li ◽

Soomin Lee ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Marrow Mesenchymal Stem Cells

BMP-2-induced migration of BMSCs can be inhibited by silencing CDC42 in vitro and in vivo.

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Melatonin Inhibits the Ferroptotic Pathway in Rat Bone Marrow Mesenchymal Stem Cells by Activating the PI3K-AKT-mTOR Signaling Axis to Attenuate Steroid-induced Osteoporosis

10.21203/rs.3.rs-850531/v1 ◽

2021 ◽

Author(s):

meng li ◽

ning yang ◽

li hao ◽

wei zhou ◽

lei li ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Mammalian Target Of Rapamycin ◽

Mtor Signaling ◽

High Dose ◽

Treatment Pathways ◽

Marrow Mesenchymal Stem Cells

Abstract ObjectivesSteroid-induced osteoporosis (SIOP) is a secondary osteoporosis, which is a systemic bone disease characterized by low bone mass, bone microstructure damage, increased bone fragility, and easy fracture. However, the specific mechanism remains unclear. Glucocorticoid-induced death of osteoblasts and bone marrow mesenchymal stem cells (BMSCs) is an important factor in SIOP. Ferroptosis is an iron-dependent programmed cell death that differs from apoptosis, cell necrosis, and autophagy, which can be induced by many factors. Herein, we aimed to explore whether glucocorticoids (GCs) cause ferroptosis in BMSCs and determine possible treatment pathways and mechanisms of action. Melatonin (MT), a hormone secreted by the pineal gland, displays strong antioxidant abilities to scavenge free radicals and alleviates ferroptosis in many tissues and organs. MethodsIn this study, we used high-dose dexamethasone (DEX) to observe whether glucocorticoids induced ferroptosis in BMSCs. We then assessed whether MT can inhibit the ferroptotic pathway, thereby providing early protection against GC-induced SIOP, and investigated the signaling pathways involved.ResultsIn vitro experiments showed that MT intervention significantly improved GC-induced ferroptosis in BMSCs and significantly improved SIOP in vivo. Pathway analysis showed that MT improves ferroptosis by activating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) axis. MT upregulates expression of PI3K, which is an important regulator of ferroptosis resistance. PI3K activators mimic the anti-ferroptosis effect of MT, but after blocking the PI3K pathway, the effect of MT is weakened. Obviously, MT can protect against SIOP induced by GC. Notably, even after GC-induced ferroptosis begins, MT can confer protection against SIOP. ConclusionOur research confirms that GC-induced ferroptosis is closely related to SIOP. Melatonin can inhibit ferroptosis by activating the PI3K-AKT-mTOR signaling pathway, thereby reducing the occurrence of steroid-induced osteoporosis. Therefore, MT may provide a novel strategy for preventing and treating SIOP.

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The negatively charged microenvironment of collagen hydrogels regulates the chondrogenic differentiation of bone marrow mesenchymal stem cells in vitro and in vivo

Journal of Materials Chemistry B ◽

10.1039/d0tb00172d ◽

2020 ◽

Vol 8 (21) ◽

pp. 4680-4693

Author(s):

Jirong Yang ◽

Yumei Xiao ◽

Zizhao Tang ◽

Zhaocong Luo ◽

Dongxiao Li ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Protein Adsorption ◽

Cell Morphology ◽

Chondrogenic Differentiation ◽

Collagen Hydrogels ◽

Marrow Mesenchymal Stem Cells

The different negatively charged microenvironments of collagen hydrogels affect the protein adsorption, cell morphology, and chondrogenic differentiation of BMSCs in vitro and in vivo.

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Kartogenin enhances the therapeutic effect of bone marrow mesenchymal stem cells derived exosomes in cartilage repair

Nanomedicine ◽

10.2217/nnm-2019-0208 ◽

2020 ◽

Vol 15 (3) ◽

pp. 273-288 ◽

Cited By ~ 1

Author(s):

Chun Liu ◽

Yun Li ◽

Zhijian Yang ◽

Zhiyou Zhou ◽

Zhihao Lou ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Therapeutic Effect ◽

Bone Marrow Mscs ◽

In Vivo Experiments ◽

Marrow Mesenchymal Stem Cells ◽

Cartilage Diseases

The effectiveness of mesenchymal stem cells (MSC) in the treatment of cartilage diseases has been demonstrated to be attributed to the paracrine mechanisms, especially the mediation of exosomes. But the exosomes derived from unsynchronized MSCs may be nonhomogeneous and the therapeutic effect varies between samples. Aim: To produce homogeneous and more effective exosomes for the regeneration of cartilage. Materials & methods: In this study we produced specific exosomes from bone marrow MSCs (BMSC) through kartogenin (KGN) preconditioning and investigated their performance in either in vitro or in vivo experiments. Results & conclusion: The exosomes derived from KGN-preconditioned BMSCs (KGN-BMSC-Exos) performed more effectively than the exosomes derived from BMSCs (BMSC-Exos). KGN preconditioning endowed BMSC-Exos with stronger chondral matrix formation and less degradation.

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Acceleration of Bone Regeneration in Critical-Size Defect Using BMP-9-Loaded nHA/ColI/MWCNTs Scaffolds Seeded with Bone Marrow Mesenchymal Stem Cells

BioMed Research International ◽

10.1155/2019/7343957 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Ran Zhang ◽

Xuewen Li ◽

Yao Liu ◽

Xiaobo Gao ◽

Tong Zhu ◽

...

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Bone Tissue Engineering ◽

Bone Tissue ◽

Composite Scaffold ◽

Marrow Mesenchymal Stem Cells

Biocompatible scaffolding materials play an important role in bone tissue engineering. This study sought to develop and characterize a nano-hydroxyapatite (nHA)/collagen I (ColI)/multi-walled carbon nanotube (MWCNT) composite scaffold loaded with recombinant bone morphogenetic protein-9 (BMP-9) for bone tissue engineering by in vitro and in vivo experiments. The composite nHA/ColI/MWCNT scaffolds were fabricated at various concentrations of MWCNTs (0.5, 1, and 1.5% wt) by blending and freeze drying. The porosity, swelling rate, water absorption rate, mechanical properties, and biocompatibility of scaffolds were measured. After loading with BMP-9, bone marrow mesenchymal stem cells (BMMSCs) were seeded to evaluate their characteristics in vitro and in a critical sized defect in Sprague-Dawley rats in vivo. It was shown that the 1% MWCNT group was the most suitable for bone tissue engineering. Our results demonstrated that scaffolds loaded with BMP-9 promoted differentiation of BMMSCs into osteoblasts in vitro and induced more bone formation in vivo. To conclude, nHA/ColI/MWCNT scaffolds loaded with BMP-9 possess high biocompatibility and osteogenesis and are a good candidate for use in bone tissue engineering.

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Transcription factor Mohawk controls tenogenic differentiation of bone marrow mesenchymal stem cells in vitro and in vivo

Journal of Orthopaedic Research® ◽

10.1002/jor.22750 ◽

2014 ◽

Vol 33 (1) ◽

pp. 1-8 ◽

Cited By ~ 46

Author(s):

Koji Otabe ◽

Hiroyuki Nakahara ◽

Akihiko Hasegawa ◽

Tetsuya Matsukawa ◽

Fumiaki Ayabe ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Transcription Factor ◽

Tenogenic Differentiation ◽

Marrow Mesenchymal Stem Cells

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Cartilage Derived from Bone Marrow Mesenchymal Stem Cells Expresses Lubricin In Vitro and In Vivo

PLoS ONE ◽

10.1371/journal.pone.0148777 ◽

2016 ◽

Vol 11 (2) ◽

pp. e0148777 ◽

Cited By ~ 26

Author(s):

Yusuke Nakagawa ◽

Takeshi Muneta ◽

Koji Otabe ◽

Nobutake Ozeki ◽

Mitsuru Mizuno ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Marrow Mesenchymal Stem Cells

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Recent Advances in Hydroxyapatite Scaffolds Containing Mesenchymal Stem Cells

Stem Cells International ◽

10.1155/2015/305217 ◽

2015 ◽

Vol 2015 ◽

pp. 1-13 ◽

Cited By ~ 27

Author(s):

John Michel ◽

Matthew Penna ◽

Juan Kochen ◽

Herman Cheung

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Tissue Regeneration ◽

Therapeutic Option ◽

Synthetic Polymers ◽

Review Article ◽

Osteogenic Lineage ◽

Wide Range

Modern day tissue engineering and cellular therapies have gravitated toward using stem cells with scaffolds as a dynamic modality to aid in differentiation and tissue regeneration. Mesenchymal stem cells (MSCs) are one of the most studied stem cells used in combination with scaffolds. These cells differentiate along the osteogenic lineage when seeded on hydroxyapatite containing scaffolds and can be used as a therapeutic option to regenerate various tissues. In recent years, the combination of hydroxyapatite and natural or synthetic polymers has been studied extensively. Due to the interest in these scaffolds, this review will cover the wide range of hydroxyapatite containing scaffolds used with MSCs forin vitroandin vivoexperiments. Further, in order to maintain a progressive scope of the field this review article will only focus on literature utilizing adult human derived MSCs (hMSCs) published in the last three years.

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