A Novel Strategy for Preparation of ADSCs-Osteogenic Microtissues Based on CEFFE and Mechanisms for Enhancing Osteogenic Activity
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PROVIDER: PRJNA985680 | ENA |
REPOSITORIES: ENA
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Project description:Bone tissue engineering is considered the optimal solution for the repair of large bone defects. Previous studies by our team have demonstrated the effectiveness of a "bottom-up" microtissue engineering strategy using bone marrow mesenchymal stem cells (BMSCs) to improve the utilization efficiency of seed cells. However, this strategy requires the extraction of bone marrow, which is associated with significant trauma and difficulties in obtaining the cells. Adipose-derived mesenchymal stem cells (ADSCs), obtained from aspirated adipose tissue, offer a less invasive and more accessible alternative, but their osteogenic capacity is noticeably weaker, severely limiting their application as seed cells in bone tissue engineering repair.Cell-free fat extract (CEFFE) is a cell-free liquid component extracted from adipose tissue, which exhibits beneficial properties such as promoting proliferation, antioxidation, anti-apoptosis, and angiogenesis. In this study, during the preparation of ADSC-based osteogenic microtissues, we first discovered that CEFFE significantly enhanced the osteogenic activity of ADSCs. Furthermore, we observed the formation of dense osteogenic membranes as early as day 7 of osteogenic induction. When the microtissues based on CEFFE-treated ADSCs were implanted subcutaneously in nude mice, we found a significant enhancement in their osteogenic activity. Finally, to further investigate the mechanism underlying the enhancement of ADSC osteogenic differentiation by CEFFE, we performed transcriptomic analysis of CEFFE-treated ADSCs and validated the activation of the key PI3K-Akt pathway using Western blotting.In conclusion, this study presents a novel approach for the preparation of ADSC-based osteogenic microtissues using CEFFE and provides insights into the mechanisms underlying the enhancement of osteogenic activity. These findings hold significant implications for the field of bone tissue engineering and offer potential advancements in the clinical translation of ADSC-based therapies.
2023-08-09 | GSE235305 | GEO
Project description:Bone regeneration is currently a major clinical challenge. Adult human mesenchymal stem cells (MSCs) possess a unique advantage in organ tissue repair and physiological function recovery. Human dental pulp derived MSCs (hDPSCs) have the dual advantages of proliferation and osteogenic differentiation abilities. They can be induced to secrete bone matrix proteins to form osteogenic microtissues by constructing an appropriate osteogenic three-dimensional microenvironment. The biological characteristics of hDPSCs from microtissues and two-dimensional cultured cells are compared using RNA sequencing. According to RNA sequencing and subsequent functional verification, the osteogenic activations of hDPSCs might be related to cell adhesion related signaling pathways. In this process, cells could sense the tension from the environment to activate related signaling pathways, such as the FAK/RhoA/Rock signaling pathway. Further, the downstream osteogenic transcription factors could be activited into the nucleus, thereby promoting the expression of osteogenic proteins.
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Project description:Mesenchymal stem cells (MSCs) are the multipotent stem cells of adult human tissues that have the ability to replicate with high proliferative rates and are responsible for the tissue renewal and regeneration. Effective osteogenic differentiation of adipose-derived stem cells (ADSCs) encourages clinical application of the cells in bone regeneration. Regeneration of damaged joints is highly dependent on the presence of MSC in synovia. Synovial membrane-derived MSCs (SM-MSCs) show good multi-lineage differentiation potential, low degree of invasiveness, and are considered as an alternative treatment strategy for arthritis-damaged tissues. Studies in MSCs from different sources identified several miRNAs important for osteogenesis. Less is known about the participation of particular miRNAs in osteogenic differentiation of SM-MSCs, the potential source of MSCs for authologous cell therapy in arthritis. In the present study, the changes in miRNA expression profile occurring during osteogenic differentiation were analyzed in human ADSCs and SM-MSCs by microarray-based and quantitative PCR approaches. We aimed at the identification of miRNAs involved in the maintenance of these MSCs and regulation of osteogenic differentiation of ADSCs and SM-MSCs.
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Project description:Construction of autonomous osteogenic microtissues based on human dental pulp derived mesenchymal stem cells
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Project description:Macrodactyly is a congenital malformation characterized by enlargement of bone and soft tissues in limbs, typically with excessive accumulation of adipose tissues. Although gain-of-function mutation of PIK3CA has been identified in macrodactyly, the mechanism of PIK3CA mutation in adipose accumulation is poorly understood. In this study, we found that adipocytes from macrodactyly were more hypertrophic than those observed in polydactyly. PIK3CA (H1047R) activating mutation and enhanced activity of PI3K/AKT pathway were detected in macrodactylous adipose-derived stem cells (Mac-ADSCs). To identify the key downstream effectors of PIK3CA activation-mediated adipogenesis in Mac-ADSCs, we examined the transcriptome of Mac-ADSCs, BYL-719 treated Mac-ADSCs and Pol-ADSCs by RNA-Seq analysis.
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Project description:Adipose-derived stem cells are angiogenic and attractive for therapeutic angiogenesis. However, ADSCs contain several subsets according to expression pattern of surface markers. We identified CD271 (LNGFR) can isolate ADSCs with superior capacity for angiogenesis. Therefore, we aimed to compare gene expression profile between CD271+ and CD271- ADSCs.
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Project description:Adipose tissue harbours a significant number of multipotent adult stem cells of mesenchymal origin known as adipose-derived stem cells (ADSCs). Broad differentiation potential and convenient accessibility of ADSCs make them an attractive source of adult mesenchymal stem cell for regenerative medicine and cell developmental plasticity research. Genome-wide microarray expression profiling was performed to identify genes deregulated during osteogenic differentiation of ADSCs to evaluate developmental plasticity of these cells. Dynamics of epigenetic modifications were analyzed in parallel and associated with the gene expression profile. Gene expression profile was analyzed in adipose-derived stem cells (ADSCs) differentiated into osteogenic lineage from 3 donors and compared to undifferentiated cells from the same donors.
2015-01-11 | E-GEOD-63754 | biostudies-arrayexpress
Project description:[1] Microarray analysis in the rat myocardial tissue: 124I-HIB transplanted MI model Vs. phosphate buffered saline (PBS) injected myocardial infarction (MI) model Vs. Sham operated model [2] Microarray analysis in the rat adipose derived stem cells: 124I-HIB-labeled ADSCs Vs. Unlabeled ADSCs [1] We investigated the change of gene expression profile in sham operated-, PBS injected- and 124I-HIB-labeled ADSCs transplanted myocardium in rat myocaridial infarction (MI) model. [2] We compared gene expression profile with 124I-HIB labeled ADSCs and unlabeled ADSCs in vitro.
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Project description:Expression data of genes and noncoding genes from the ADSCs and adipogenic-induced ADSCs
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