Melatonin-induced osteogenesis with methanol-annealed silk materials

2019 ◽  
Vol 34 (3) ◽  
pp. 291-305 ◽  
Author(s):  
Damla Çetin Altındal ◽  
Eric N James ◽  
David L Kaplan ◽  
Menemşe Gümüşderelioğlu
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Repair ◽  
Human Mesenchymal Stem Cells ◽  
Bone Tissue Regeneration ◽  
Burst Release ◽  
Continuous Release ◽  
Related Transcription Factor ◽  
Silk Films ◽  
Β Sheet

Melatonin, a hormone produced in the pineal gland, has been investigated for bone repair, remodeling, osteoporosis, as well as osseointegration of the implants. In this study, different concentrations of melatonin (0–2000-µM) were embedded into silk films annealed by methanol or water. Then, their capacity to differentiate human mesenchymal stem cells into osteoblasts was investigated for bone tissue regeneration. While methanol-annealed silk films have ~55% crystallinity, room-temperature water-annealed silk films have ~30% crystallinity by depending upon their different β-sheet contents. Melatonin-loaded silk films exhibited an initial burst release followed by a continuous release for up to 5 days, and the β-sheet content of silk films did not affect the release behavior of melatonin, an amphiphilic molecule. Moreover, human mesenchymal stem cells exhibited an increase in osteogenic markers such as alkaline phosphatase activity, osteocalcin, and runt-related transcription factor 2 expressions on the melatonin-loaded methanol-annealed silk films in both proliferation and osteogenic media. The bioactivity of the melatonin-modified silk films was further confirmed by the enhanced mineralization compared to silk films alone. This study demonstrated the feasibility of developing melatonin-loaded silk materials and the positive effect of releasing melatonin at micromolar concentrations on osteogenic differentiation of human mesenchymal stem cells cultured especially in osteogenic medium.

scholarly journals 3D Printed SiOC(N) Ceramic Scaffolds for Bone Tissue Regeneration: Improved Osteogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells

2021 ◽  
Vol 22 (24) ◽  
pp. 13676
Author(s):  
Yuejiao Yang ◽  
Apoorv Kulkarni ◽  
Gian Domenico Soraru ◽  
Joshua M. Pearce ◽  
Antonella Motta
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
3D Printing ◽  
Pore Size ◽  
Osteogenic Differentiation ◽  
Bone Tissue ◽  
Low Cost ◽  
Human Mesenchymal Stem Cells ◽  
Bone Tissue Regeneration ◽  
Gene Expressions

Bone tissue engineering has developed significantly in recent years as there has been increasing demand for bone substitutes due to trauma, cancer, arthritis, and infections. The scaffolds for bone regeneration need to be mechanically stable and have a 3D architecture with interconnected pores. With the advances in additive manufacturing technology, these requirements can be fulfilled by 3D printing scaffolds with controlled geometry and porosity using a low-cost multistep process. The scaffolds, however, must also be bioactive to promote the environment for the cells to regenerate into bone tissue. To determine if a low-cost 3D printing method for bespoke SiOC(N) porous structures can regenerate bone, these structures were tested for osteointegration potential by using human mesenchymal stem cells (hMSCs). This includes checking the general biocompatibilities under the osteogenic differentiation environment (cell proliferation and metabolism). Moreover, cell morphology was observed by confocal microscopy, and gene expressions on typical osteogenic markers at different stages for bone formation were determined by real-time PCR. The results of the study showed the pore size of the scaffolds had a significant impact on differentiation. A certain range of pore size could stimulate osteogenic differentiation, thus promoting bone regrowth and regeneration.

Limited potential of AAV-mediated gene therapy in transducing human mesenchymal stem cells for bone repair applications

Gene Therapy ◽  
2020 ◽  
Author(s):  
Sofia Bougioukli ◽  
Morgan Chateau ◽  
Heidy Morales ◽  
Venus Vakhshori ◽  
Osamu Sugiyama ◽  
...  
Keyword(s):  
Stem Cells ◽  
Gene Therapy ◽  
Mesenchymal Stem Cells ◽  
Bone Repair ◽  
Human Mesenchymal Stem Cells

scholarly journals 3D Printed SiOC(N) Ceramic Scaffolds for Bone Tissue Regeneration: Improved Osteogenic Differentiation of Human Bone Marrow‐Derived Mesenchymal Stem Cells

2021 ◽  
Author(s):  
Yuejiao Yang ◽  
Apoorv Kulkarni ◽  
Gian Domenico Soraru ◽  
Joshua M Pearce ◽  
Antonella Motta
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
3D Printing ◽  
Pore Size ◽  
Osteogenic Differentiation ◽  
Bone Tissue ◽  
Low Cost ◽  
Human Mesenchymal Stem Cells ◽  
Bone Tissue Regeneration ◽  
Gene Expressions

Bone tissue engineering has developed significantly in recent years as the increasing demand for bone substitutes due to trauma, cancer, arthritis, and infections. The scaffolds for bone regeneration need to be mechanically stable and have a 3D architecture with interconnected pores. With the advances in additive manufacturing technology, these requirements can be fulfilled by 3D printing scaffolds with controlled geometry and porosity using a low-cost multistep process. The scaffolds, however, must also be bioactive to promote the environment for the cells to regenerate into bone tissue. To determine if a low-cost 3D printing method for bespoke SiOC(N) porous structures can regenerate bone these structures were tested for osteointegration potential by using human mesenchymal stem cells (hMSCs). This includes checking the general biocompatibilities under the osteogenic differentiation environment (cell proliferation and metabolism). Moreover, cell morphology was observed by confocal microscopy and gene expressions on typical osteogenic markers at different stages for bone formation were determined by real-time PCR. The results of the study showed the pore size of the scaffolds had a significant impact on differentiation. A certain range of pore size could stimulate osteogenic differentiation, thus promoting bone regrowth and regeneration.

scholarly journals In VitroCharacterization of Human Mesenchymal Stem Cells Isolated from Different Tissues with a Potential to Promote Complex Bone Regeneration

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Áron Szepesi ◽  
Zsolt Matula ◽  
Anna Szigeti ◽  
György Várady ◽  
József Szalma ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Periodontal Ligament ◽  
Human Mesenchymal Stem Cells ◽  
Bone Grafts ◽  
Bone Tissue Regeneration ◽  
Osteogenic Potential ◽  
Medical Need

Bone tissue regeneration is a major, worldwide medical need, and several strategies have been developed to support the regeneration of extensive bone defects, including stem cell based bone grafts. In addition to the application of stem cells with high osteogenic potential, it is important to maintain proper blood flow in a bone graft to avoid inner graft necrosis. Mesenchymal stem cells (MSCs) may form both osteocytes and endothelial cells; therefore we examined the combinedin vitroosteogenic and endothelial differentiation capacities of MSCs derived from adipose tissue, Wharton’s jelly, and periodontal ligament. Based on a detailed characterization presented here, MSCs isolated from adipose tissue and periodontal ligament may be most appropriate for generating vascularized bone grafts.

scholarly journals Recent Advances in Mechanically Loaded Human Mesenchymal Stem Cells for Bone Tissue Engineering

2020 ◽  
Vol 21 (16) ◽  
pp. 5816
Author(s):  
Kar Wey Yong ◽  
Jane Ru Choi ◽  
Jean Yu Choi ◽  
Alistair C. Cowie
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Graft ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Mechanical Loading ◽  
Bone Repair ◽  
Human Mesenchymal Stem Cells ◽  
Bone Defects

Large bone defects are a major health concern worldwide. The conventional bone repair techniques (e.g., bone-grafting and Masquelet techniques) have numerous drawbacks, which negatively impact their therapeutic outcomes. Therefore, there is a demand to develop an alternative bone repair approach that can address the existing drawbacks. Bone tissue engineering involving the utilization of human mesenchymal stem cells (hMSCs) has recently emerged as a key strategy for the regeneration of damaged bone tissues. However, the use of tissue-engineered bone graft for the clinical treatment of bone defects remains challenging. While the role of mechanical loading in creating a bone graft has been well explored, the effects of mechanical loading factors (e.g., loading types and regime) on clinical outcomes are poorly understood. This review summarizes the effects of mechanical loading on hMSCs for bone tissue engineering applications. First, we discuss the key assays for assessing the quality of tissue-engineered bone grafts, including specific staining, as well as gene and protein expression of osteogenic markers. Recent studies of the impact of mechanical loading on hMSCs, including compression, perfusion, vibration and stretching, along with the potential mechanotransduction signalling pathways, are subsequently reviewed. Lastly, we discuss the challenges and prospects of bone tissue engineering applications.

scholarly journals Modeled Microgravity Inhibits Osteogenic Differentiation of Human Mesenchymal Stem Cells and Increases Adipogenesis

Endocrinology ◽  
2004 ◽  
Vol 145 (5) ◽  
pp. 2421-2432 ◽  
Author(s):  
Majd Zayzafoon ◽  
William E. Gathings ◽  
Jay M. McDonald
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Transcription Factor ◽  
Bone Loss ◽  
Osteogenic Differentiation ◽  
Glucose Transporter ◽  
Human Mesenchymal Stem Cells ◽  
Osteoblastic Differentiation ◽  
Peroxisome Proliferator ◽  
Related Transcription Factor

Abstract Space flight-induced bone loss has been attributed to a decrease in osteoblast function, without a significant change in bone resorption. To determine the effect of microgravity (MG) on bone, we used the Rotary Cell Culture System [developed by the National Aeronautics and Space Administration (NASA)] to model MG. Cultured mouse calvariae demonstrated a 3-fold decrease in alkaline phosphatase (ALP) activity and failed to mineralize after 7 d of MG. ALP and osteocalcin gene expression were also decreased. To determine the effects of MG on osteoblastogenesis, we cultured human mesenchymal stem cells (hMSC) on plastic microcarriers, and osteogenic differentiation was induced immediately before the initiation of modeled MG. A marked suppression of hMSC differentiation into osteoblasts was observed because the cells failed to express ALP, collagen 1, and osteonectin. The expression of runt-related transcription factor 2 was also inhibited. Interestingly, we found that peroxisome proliferator-activated receptor γ (PPARγ2), which is known to be important for adipocyte differentiation, adipsin, leptin, and glucose transporter-4 are highly expressed in response to MG. These changes were not corrected after 35 d of readaptation to normal gravity. In addition, MG decreased ERK- and increased p38-phosphorylation. These pathways are known to regulate the activity of runt-related transcription factor 2 and PPARγ2, respectively. Taken together, our findings indicate that modeled MG inhibits the osteoblastic differentiation of hMSC and induces the development of an adipocytic lineage phenotype. This work will increase understanding and aid in the prevention of bone loss, not only in MG but also potentially in age-and disuse-related osteoporosis.

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