Mesenchymal Stem Cells
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Jun Li ◽  
Wenzhao Wang ◽  
Mingxin Li ◽  
Ping Song ◽  
Haoyuan Lei ◽  

Large-segment bone defect caused by trauma or tumor is one of the most challenging problems in orthopedic clinics. Biomimetic materials for bone tissue engineering have developed dramatically in the past few decades. The organic combination of biomimetic materials and stem cells offers new strategies for tissue repair, and the fate of stem cells is closely related to their extracellular matrix (ECM) properties. In this study, a photocrosslinked biomimetic methacrylated gelatin (Bio-GelMA) hydrogel scaffold was prepared to simulate the physical structure and chemical composition of the natural bone extracellular matrix, providing a three-dimensional (3D) template and extracellular matrix microenvironment. Bone marrow mesenchymal stem cells (BMSCS) were encapsulated in Bio-GelMA scaffolds to examine the therapeutic effects of ECM-loaded cells in a 3D environment simulated for segmental bone defects. In vitro results showed that Bio-GelMA had good biocompatibility and sufficient mechanical properties (14.22kPa). A rat segmental bone defect model was constructed in vivo. The GelMA-BMSC suspension was added into the PDMS mold with the size of the bone defect and photocured as a scaffold. BMSC-loaded Bio-GelMA resulted in maximum and robust new bone formation compared with hydrogels alone and stem cell group. In conclusion, the bio-GelMA scaffold can be used as a cell carrier of BMSC to promote the repair of segmental bone defects and has great potential in future clinical applications.

2021 ◽  
Beilei Ma ◽  
Tengkai Wang ◽  
Juan Li ◽  
Qian Wang

Abstract Background Angiogenesis is required in many physiological conditions, including bone regeneration, wound healing, and tissue regeneration. Cell-derived extracellular matrix (CD-ECM) could guide intricate cellular and tissue processes such as homeostasis, healing and regeneration. Methods The purpose of this study is to explore the effect and mechanism of ECM derived from decellularized Wharton's Jelly-derived mesenchymal stem cells (WJ-MSCs) on endothelial cell viability and angiogenesis. Results In this study, we found for the first time that WJ-MSCs ECM could improve the angiogenesis ability of human umbilical vein endothelial cells (HUVECs) with a time-dependent manner in vitro. Mechanically, WJ-MSCs ECM activated the focal adhesion kinase (FAK)/P38 signaling pathway via integrin αVβ3, which further promoted the expression of the cellular (c)-Myc. Further, c-Myc increased histone acetylation levels of the vascular endothelial growth factor (VEGF) promoter by recruiting P300, which ultimately promoting VEGF expression. Conclusions Extracellular matrix derived from Wharton’s Jelly-derived mesenchymal stem cells promotes angiogenesis via integrin αVβ3/c-Myc/P300/VEGF. This study is expected to provide a new approach to promote angiogenesis in bone and tissue regeneration.

2022 ◽  
Vol 145 ◽  
pp. 112473
Aljohra M. Al-Otaibi ◽  
Asma S. Al-Gebaly ◽  
Rafa Almeer ◽  
Gadah Albasher ◽  
Wedad S. Al-Qahtani ◽  

2021 ◽  
Meik Neufurth ◽  
Shunfeng Wang ◽  
Heinz C. Schröder ◽  
Bilal Al-Nawas ◽  
Xiaohong Wang ◽  

Abstract The three-dimensional (3D)-printing processes reach increasing recognition as important fabrication techniques to meet the growing demands in tissue engineering. However, it is imperative to fabricate 3D tissue units, which contain cells that have the property to be regeneratively active. In most bio-inks, a metabolic energy-providing component is missing. Here a formulation of a bio-ink is described, which is enriched with polyphosphate (polyP), a metabolic energy providing physiological polymer. The bio-ink composed of a scaffold (N,O-carboxymethyl chitosan), a hydrogel (alginate) and a cell adhesion matrix (gelatin) as well as polyP substantially increases the viability and the migration propensity of mesenchymal stem cells (MSC). In addition, this ink stimulates not only the growth but also the differentiation of MSC to mineral depositing osteoblasts. Furthermore, the growth/aggregate pattern of MSC changes from isolated cells to globular spheres, if embedded in the polyP bio-ink. The morphogenetic activity of the MSC exposed to polyP in the bio-ink is corroborated by qRT-PCR data, which show a strong induction of the steady-state-expression of alkaline phosphatase, connected with a distinct increase in the expression ratio between RUNX2 and Sox2. We propose that polyP should become an essential component in bio-inks for the printing of cells that retain their regenerative activity.

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