Can Dynamic Compression in the Absence of Growth Factors Induce Chondrogenic Differentiation of Bone Marrow Derived MSCs Encapsulated in Agarose Hydrogels?

The authors studied the influence of the combination of TGF? and IGF growth factors, as well as the differentiation time, on the induction of MSC chondrogenesis in vitro. It is proved that MSCs located in 2D and 3D systems, when exposed to TGF?/ IGF, showed the signs of early chondroblast-like cells in 7 days. The TGF?/ IGF used for the induction of MSCs is more preferred, because it results in a more pronounced hypertrophic-suppression effect. The absence of significant differences in gene expression (excepting Sox9) on the 7th and 21st days of chondrogenic differentiation allows the process to be reduced in vitro to 7 days.

Download Full-text

Effect of Activated Platelet-Rich Plasma on Chondrogenic Differentiation of Rabbit Bone Marrow-Derived Mesenchymal Stem Cells

10.21203/rs.3.rs-306482/v1 ◽

2021 ◽

Author(s):

Zhen Wang ◽

Zheng Wang ◽

Bin Zhang ◽

Qinghua Zhao ◽

Yubao Liu ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Growth Factors ◽

Chondrogenic Differentiation ◽

Platelet Rich Plasma ◽

Cell Counting ◽

Chondrogenic Medium ◽

Tissue Repair And Regeneration ◽

Rabbit Bone

Abstract Background Platelet-rich plasma (PRP) has revealed benefits in tissue repair and regeneration, however, the effect of PRP on proliferation and chondrogenesis of mesenchymal stem cells remains controversial.This study is to evaluate the effect of different concentration PRP on proliferation and chondrogenic differentiation of rabbit bone marrow-derived mesenchymal stem cells(BMSCs). Methods PRP was obtained by centrifugation and activation, in which growth factors and cytokines were detected. BMSCs were isolated from rabbit bone marrow and characterized by flow cytometry. About 5 × 103 BMSCs were cultured in high glucose Dulbecco’s modified Eagle’s medium (HG-DMEM) with 4 different compositions: 10% fetal bovine serum, 5%PRP, 10%PRP, and 15%PRP for consecutive 7 days. Cell counting assays were performed on days 1, 3, 5, and 7 to evaluate the BMSCs proliferation. In chondrogenic differentiation, high-density cell pellets composed of 5 × 105 BMSCs were induced in 4 conditions: commercial chondrogenic medium (control), 5%PRP (HG-DMEM + 5%PRP), 10%PRP (HG-DMEM + 10%PRP), and 15%PRP (HG-DMEM + 15%PRP) for 21 days. The gene expression levels of aggrecan (ACAN), collagen type Ⅱ Alpha 1 (COL2A1), and SRY-Box Transcription Factor 9 (SOX9) in pellets were detected. Histological assessments were performed by morphologically observation and pathological stain. Independent-samples t-test and one-way analysis of variance were used in statistical analyses. Results The concentrations of growth factors and cytokines were elevated in PRP. BMSCs proliferation was enhanced in all groups, and 10% PRP revealed more obvious outcome than the others from day 5. In chondrogenic differentiation, the levels of ACAN, COL2A1, and SOX9 were lower in 3 PRP groups than control, but ACAN and SOX9 was higher in 10% PRP group than 5% and 15%. Histological examinations showed 10% PRP-treated pellets showed more regular appearance, larger size, and abundant extracellular matrix than 5% and 10% groups, but still inferior to commercial chondrogenic medium. Conclusions PRP may enhance the proliferation of rabbit BMSCs, while with limited effect on chondrogenic differentiation compared with commercial chondrogenic medium in pellets culture. Whether optimizing and modifying PRP components would lead to satisfying chondrogenesis of BMSCs, it is deserved furthermore study.

Download Full-text

Cell-Matrix Interactions Modulate Mesenchymal Stem Cell Response to Dynamic Compression

ASME 2011 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2011-53334 ◽

2011 ◽

Author(s):

Stephen D. Thorpe ◽

Conor T. Buckley ◽

Andrew J. Steward ◽

Daniel J. Kelly

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Growth Factors ◽

Chondrogenic Differentiation ◽

Dynamic Compression ◽

Compressive Loading ◽

Cell Matrix ◽

Matrix Interactions ◽

Cell Matrix Interactions

Unconfined cyclic compressive loading has been shown to promote the chondrogenic differentiation of agarose encapsulated mesenchymal stem cells (MSCs) in the absence of chondrogenic growth factors [1, 2]. However, in general robust chondrogenesis has not been reported as a result of mechanical stimulation alone; with biochemical stimulation through TGF-β supplementation yielding a more potent pro-chondrogenic effect [2, 3].

Download Full-text

Faculty Opinions recommendation of Chondrogenic differentiation of human bone marrow stem cells in transwell cultures: generation of scaffold-free cartilage.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1092483.546928 ◽

2007 ◽

Author(s):

Dietmar Werner Hutmacher

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Chondrogenic Differentiation ◽

Bone Marrow Stem Cells ◽

Human Bone ◽

Human Bone Marrow

Download Full-text

Protective Effects of a Hyaluronan-Binding Peptide (P15-1) on Mesenchymal Stem Cells in an Inflammatory Environment

International Journal of Molecular Sciences ◽

10.3390/ijms22137058 ◽

2021 ◽

Vol 22 (13) ◽

pp. 7058

Author(s):

Thorsten Kirsch ◽

Fenglin Zhang ◽

Olivia Braender-Carr ◽

Mary K. Cowman

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Chondrogenic Differentiation ◽

Therapeutic Strategy ◽

Cartilage Defects ◽

Mrna Levels ◽

Protective Effects ◽

Human Bmscs ◽

Hyaluronan Binding

Mesenchymal stem cells (MSCs) obtained from various sources, including bone marrow, have been proposed as a therapeutic strategy for the improvement of tissue repair/regeneration, including the repair of cartilage defects or lesions. Often the highly inflammatory environment after injury or during diseases, however, greatly diminishes the therapeutic and reparative effectiveness of MSCs. Therefore, the identification of novel factors that can protect MSCs against an inflammatory environment may enhance the effectiveness of these cells in repairing tissues, such as articular cartilage. In this study, we investigated whether a peptide (P15-1) that binds to hyaluronan (HA), a major component of the extracellular matrix of cartilage, protects bone-marrow-derived MSCs (BMSCs) in an inflammatory environment. The results showed that P15-1 reduced the mRNA levels of catabolic and inflammatory markers in interleukin-1beta (IL-1β)-treated human BMSCs. In addition, P15-1 enhanced the attachment of BMSCs to HA-coated tissue culture dishes and stimulated the chondrogenic differentiation of the multipotential murine C3H/10T1/2 MSC line in a micromass culture. In conclusion, our findings suggest that P15-1 may increase the capacity of BMSCs to repair cartilage via the protection of these cells in an inflammatory environment and the stimulation of their attachment to an HA-containing matrix and chondrogenic differentiation.

Download Full-text

Effect of hematopoietic growth factors on MR images of bone marrow in children undergoing chemotherapy.

Radiology ◽

10.1148/radiology.189.3.7694312 ◽

1993 ◽

Vol 189 (3) ◽

pp. 745-751 ◽

Cited By ~ 75

Author(s):

B D Fletcher ◽

J E Wall ◽

S L Hanna

Keyword(s):

Bone Marrow ◽

Growth Factors ◽

Mr Images ◽

Hematopoietic Growth Factors

Download Full-text

Exosome-transported circRNA_0001236 enhances chondrogenesis and suppress cartilage degradation via the miR-3677-3p/Sox9 axis

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02431-5 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Guping Mao ◽

Yiyang Xu ◽

Dianbo Long ◽

Hong Sun ◽

Hongyi Li ◽

...

Keyword(s):

Bone Marrow ◽

Mouse Model ◽

Chondrogenic Differentiation ◽

Cartilage Degradation ◽

Human Bone ◽

Human Bone Marrow ◽

Luciferase Reporter ◽

Gene And Protein Expression

Abstract Objectives Aberrations in exosomal circular RNA (circRNA) expression have been identified in various human diseases. In this study, we investigated whether exosomal circRNAs could act as competing endogenous RNAs (ceRNAs) to regulate the pathological process of osteoarthritis (OA). This study aimed to elucidate the specific MSC-derived exosomal circRNAs responsible for MSC-mediated chondrogenic differentiation using human bone marrow-derived MSCs (hMSCs) and a destabilization of the medial meniscus (DMM) mouse model of OA. Methods Exosomal circRNA deep sequencing was performed to evaluate the expression of circRNAs in human bone marrow-derived MSCs (hMSCs) induced to undergo chondrogenesis from day 0 to day 21. The regulatory and functional roles of exosomal circRNA_0001236 were examined on day 21 after inducing chondrogenesis in hMSCs and were validated in vitro and in vivo. The downstream target of circRNA_0001236 was also explored in vitro and in vivo using bioinformatics analyses. A luciferase reporter assay was used to evaluate the interaction between circRNA_0001236 and miR-3677-3p as well as the target gene sex-determining region Y-box 9 (Sox9). The function and mechanism of exosomal circRNA_0001236 in OA were explored in the DMM mouse model. Results Upregulation of exosomal circRNA_0001236 enhanced the expression of Col2a1 and Sox9 but inhibited that of MMP13 in hMSCs induced to undergo chondrogenesis. Moreover, circRNA_0001236 acted as an miR-3677-3p sponge and functioned in human chondrocytes via targeting miR-3677-3p and Sox9. Intra-articular injection of exosomal circRNA_0001236 attenuated OA in the DMM mouse model. Conclusions Our results reveal an important role for a novel exosomal circRNA_0001236 in chondrogenic differentiation. Overexpression of exosomal circRNA_0001236 promoted cartilage-specific gene and protein expression through the miR-3677-3p/Sox9 axis. Thus, circRNA_0001236-overexpressing exosomes may alleviate cartilage degradation, suppressing OA progression and enhancing cartilage repair. Our findings provide a potentially effective therapeutic strategy for treating OA.

Download Full-text