MMP13-Overexpressing Mesenchymal Stem Cells Enhance Bone Tissue Formation in the Presence of Collagen Hydrogel

BACKGROUND@#Matrix metalloproteinases (MMPs) are proteins involved in the repair and remodeling the extracellular matrix (ECM). MMP13 is essential for bone development and healing through the remodeling of type I collagen (COL1), the main component of the ECM in bone tissue. Mesenchymal stem cells (MSCs)-based cell therapy has been considered a promising approach for bone regeneration because of their osteogenic properties. However, the approaches using MSC to completely regenerate bone tissue have been limited. To overcome the limitation, genetic engineering of MSC could be a strategy for promoting regeneration efficacy. @*METHODS@#We performed in vitro and in vivo experiments using MMP13-overexpressing MSCs in the presence of COL1. To examine MMP13-overexpressing MSCs in vivo, we prepared a fibrin/COL1-based hydrogel to encapsulate MSCs and subcutaneously implanted gel-encapsulated MSCs in nude mice.We found that the osteogenic marker genes, ALP and RUNX2, were upregulated in MMP13-overexpressing MSCs through p38 phosphorylation. In addition, MMP13 overexpression in MSCs stimulated the expression of integrin a3, which is upstream receptor of p38, and substantially increased osteogenic differentiation potential of MSCs. Bone tissue formation in MMP13-overexpressing MSCs was significantly higher than that in control MSCs. Taken together, our findings demonstrate that MMP13 is not only an essential factor for bone development and bone healing but also has a pivotal role in promoting osteogenic differentiation of MSCs to induce bone formation. @*CONCLUSION@#MSCs Genetically engineered to overexpress MMP13, which have a powerful potential to differentiate into the osteogenic cells, might be beneficial in bone disease therapy.

Combinatorial Effect of Mesenchymal Stem Cells and Extracellular Vesicles in a Hydrogel on Cartilage Regeneration

BACKGROUND@#Mesenchymal stem cells (MSCs) are used for tissue regeneration due to their wide differentiation capacity and anti-inflammatory effects. Extracellular vesicles (EVs) derived from MSCs are also known for their regenerative effects as they contain nucleic acids, proteins, lipids, and cytokines similar to those of parental cells. There are several studies on the use of MSCs or EVs for tissue regeneration. However, the combinatorial effect of human MSCs (hMSCs) and EVs is not clear. In this study, we investigated the combinatorial effect of hMSCs and EVs on cartilage regeneration via co-encapsulation in a hyaluronic-acid (HA)-based hydrogel. @*METHODS@#A methacrylic-acid-based HA hydrogel was prepared to encapsulate hMSCs and EVs in hydrogels. Through in vitro and in vivo analyses, we investigated the chondrogenic potential of the HA hydrogel-encapsulated with hMSCs and EVs. @*RESULTS@#Co-encapsulation of hMSCs with EVs in the HA hydrogel increased the chondrogenic differentiation of hMSCs and regeneration of damaged cartilage tissue compared with that of the HA hydrogel loaded with hMSCs only. @*CONCLUSION@#Co-encapsulation of hMSCs and EVs in the HA hydrogel effectively enhances cartilage tissue regeneration due to the combinatorial therapeutic effect of hMSCs and EVs. Thus, in addition to cartilage tissue regeneration for the treatment of osteoarthritis, this approach would be a useful strategy to improve other types of tissue regeneration.

Suppression of the ERK–SRF axis facilitates somatic cell reprogramming

The molecular mechanism underlying the initiation of somatic cell reprogramming into induced pluripotent stem cells (iPSCs) has not been well described. Thus, we generated single-cell-derived clones by using a combination of drug-inducible vectors encoding transcription factors (Oct4, Sox2, Klf4 and Myc) and a single-cell expansion strategy. This system achieved a high reprogramming efficiency after metabolic and epigenetic remodeling. Functional analyses of the cloned cells revealed that extracellular signal-regulated kinase (ERK) signaling was downregulated at an early stage of reprogramming and that its inhibition was a driving force for iPSC formation. Among the reprogramming factors, Myc predominantly induced ERK suppression. ERK inhibition upregulated the conversion of somatic cells into iPSCs through concomitant suppression of serum response factor (SRF). Conversely, SRF activation suppressed the reprogramming induced by ERK inhibition and negatively regulated embryonic pluripotency by inducing differentiation via upregulation of immediate early genes, such as c-Jun, c-Fos and EGR1. These data reveal that suppression of the ERK-SRF axis is an initial molecular event that facilitates iPSC formation and may be a useful surrogate marker for cellular reprogramming.

Poor Capability of 3D-Cultured Adipose-Derived Stem Cells to Induce Hair Follicles in Contrast to 3D-Cultured Dermal Papilla Cells

No abstract available.

Poor Capability of 3D-Cultured Adipose-Derived Stem Cells to Induce Hair Follicles in Contrast to 3D-Cultured Dermal Papilla Cells

No abstract available.

Microengineered Platforms for Co-Cultured Mesenchymal Stem Cells towards Vascularized Bone Tissue Engineering

Bone defects are common disease requiring thorough treatments since the bone is a complex vascularized tissue that is composed of multiple cell types embedded within an intricate extracellular matrix (ECM). For past decades, tissue engineering using cells, proteins, and scaffolds has been suggested as one of the promising approaches for effective bone regeneration. Recently, many researchers have been interested in designing effective platform for tissue regeneration by orchestrating factors involved in microenvironment around tissues. Among factors affecting bone formation, vascularization during bone development and after minor insults via endochondral and intramembranous ossification is especially critical for the long-term support for functional bone. In order to create vascularized bone constructs, the interactions between human mesenchymal stem cells (MSCs) and endothelial cells (ECs) have been investigated using both direct and indirect co-culture studies. Recently, various culture methods including micropatterning techniques, three dimensional scaffolds, and microfluidics have been developed to create micro-engineered platforms that mimic the nature of vascularized bone formation, leading to the creation of functional bone structures. This review focuses on MSCs co-cultured with endothelial cells and micro-engineered platforms to determine the underlying interplay between co-cultured MSCs and vascularized bone constructs, which is ultimately necessary for adequate regeneration of bone defects.

An optimization of onebody type implant system considering various design parameters / 대한치과보철학회지

STATEMENT OF PROBLEM: The researches on the influence of design variables on the stress distribution in cortical and trabecular bones and on optimal design for implant system were limited. PURPOSE: The purpose of this study is to identify the sensitivities of design parameters and to suggest the optimal parameters for designing the onebody type implant system. MATERIAL AND METHODS: Stresses arising in the implant system were obtained by finite element analysis using a three dimensional model. An onebody type implant system [Oneplant (Warrantec. Co. Ltd., Korea)]was considered in this study. Vertical load(150 N) was applied on the top of the abutment along the axial direction. The initial design variables set for sensitivity analysis were radius of fixture, numbers of micro thread, numbers of power thread, height of micro thread, fixture length, tapered angle of fixture, inclined angle of thread, width of micro thread and width of power thread. The statistical technique of Design of Experiments(DOE) was applied to the simulation model to deduce effective design parameters on stress distributions in bones. The deduced design parameters were incorporated into a fully automated design tool which is coupled with the finite element analysis and numerical optimization to determine the optimal design parameters. RESULTS: 1. The result of sensitivity analysis showed six design variables - radius of fixture, tapered angle of fixture, inclined angle of thread, numbers of power thread, numbers of micro thread and height of micro thread - were more influential than the others. 2. The optimal values of design variables can be deduced by coupling finite element analysis (FEA) and design optimization tool(DOT).

Three-dimensional finite element analysis of stress distribution and preload of different connection types implant with initial clamping / 대한치과보철학회지

STATEMENT OF PROBLEM: One of common problems associated with single teeth dental implant prosthetic is the loosening of screws that retain the implants. PURPOSE: The maintenance of screw joint stability is considered a function of the preload achieved in the screw when the suggested initial tightening torque is applied. The purpose of this study was to investigate acquired preload after initial clamping torque for estimating screw joint stability. MATERIAL AND METHODS: A comparative study on the effect of initial clamping of two types of implant systems with different connections was conducted. Three dimensional non-linear finite element analysis is adopted to compare the characteristics of screw preloads and stress distributions between two different types of implant systems composed with abutment, screw, and fixture under the same loading and boundary conditions. RESULTS: 1. When the initial clamping torque of 32Ncm was applied to the implant systems, all types of implants generated the maximum effective stress at the first helix region of screw. 2. Morse taper connection types of implants generate lower stress distributions compared to those by butt joint connection types of implants due to large contact surface between abutment and fixture. 3. The internal types of implant systems with friction grip type implant systems have higher resistance to screw loosening than that of the external types of implant systems since the internal types of implant systems generated larger preload than that generated by the external types for the same tightening moments.

Three-dimensional stress analysis of implant systems in the mandibular bone with various abutment types and loading conditions / 대한치과보철학회지

STATEMENT OF PROBLEM: There are many studies focused on the effect of shape of fixtures on stress distribution in the mandibular bone. However, there are no studies focused on the effect of the abutment types on stress distribution in mandibular bone. PURPOSE: The purpose of this study is to investigate the effect of three different abutment types on the stress distributions in the mandibular bone due to various loads by performing finite element analysis. Material and method : Three different implant systems produced by Warantec (Seoul, Korea) were modeled to study the effect of abutment types on the stress distribution in the mandibular bone. The three implant systems are classified into oneplant (Oneplant, OP-TH-S11.5), internal implant (Inplant, IO-S11.5) and external implant (Hexplant, EH-S11.5). All abutments were made of titanium grade ELI, and all fixtures were made of titanium grade IV. The mandibular bone used in this study is constituted of compact and spongeous bone assumed to be homogeneous, isotropic and linearly elastic. A comparative study of stress distributions in the mandibular bone with three different types of abutment was conducted. RESULTS: It was found that the types of abutments have significant influence on the stress distribution in the mandibular bone. It was due to difference in the load transfer mechanism and the size of contact area between abutment and fixture. Also the maximum effective stress in the mandibular bone was increased with the increase of inclination angle of load. CONCLUSION: It was concluded that the maximum effective stress in the bone by the internal implant was the lowest among the maximum effective stresses by other two types.