scholarly journals Effect of Compression Loading on Human Nucleus Pulposus-Derived Mesenchymal Stem Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Hang Liang ◽  
Sheng Chen ◽  
Donghua Huang ◽  
Xiangyu Deng ◽  
Kaige Ma ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Nucleus Pulposus ◽  
Colony Formation ◽  
Cellular Therapy ◽  
Biological Behavior ◽  
Compression Loading ◽  
Ivd Degeneration ◽  
Related Proteins

Purpose. Mechanical loading plays a vital role in the progression of intervertebral disc (IVD) degeneration, but little is known about the effect of compression loading on human nucleus pulposus-derived mesenchymal stem cells (NP-MSCs). Thus, this study is aimed at investigating the effect of compression on the biological behavior of NP-MSCs in vitro. Methods. Human NP-MSCs were isolated from patients undergoing lumbar discectomy for IVD degeneration and were identified by immunophenotypes and multilineage differentiation. Then, cells were cultured in the compression apparatus at 1.0 MPa for different times (0 h, 24 h, 36 h, and 48 h). The viability-, differentiation-, and differentiation-related genes (Runx2, APP, and Col2) and colony formation-, migration-, and stem cell-related proteins (Sox2 and Oct4) were evaluated. Results. The results showed that the isolated cells fulfilled the criteria of MSC stated by the International Society for Cellular Therapy (ISCT). And our results also indicated that compression loading significantly inhibited cell viability, differentiation, colony formation, and migration. Furthermore, gene expression suggested that compression loading could downregulate the expression of stem cell-related proteins and lead to NP-MSC stemness losses. Conclusions. Our results suggested that the biological behavior of NP-MSCs could be inhibited by compression loading and therefore enhanced our understanding on the compression-induced endogenous repair failure of NP-MSCs during IVDD.

scholarly journals Pioglitazone Protects Compression-Mediated Apoptosis in Nucleus Pulposus Mesenchymal Stem Cells by Suppressing Oxidative Stress

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Yiqiang Hu ◽  
Liang Huang ◽  
Min Shen ◽  
Yunlu Liu ◽  
Guohui Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Cellular Therapy ◽  
Adverse Outcomes ◽  
Protective Effects ◽  
Apoptosis Pathway ◽  
Ivd Degeneration

Excessive compression, the main cause of intervertebral disc (IVD) degeneration, affected endogenous repair of the intervertebral disc. Pioglitazone (PGZ) is the agonist of peroxisome proliferator-activated receptor γ, which has been widely used in the treatment of diabetes mellitus. The present study aim at investigating whether pioglitazone has protective effects on compression-mediated cell apoptosis in nucleus pulposus mesenchymal stem cells (NP-MSCs) and further exploring the possible underlying mechanism. Our results indicated that the isolated cells satisfied the criteria of MSC stated by the International Society for Cellular Therapy. Besides, our research revealed that pioglitazone could protect cell viability, cell proliferation of NP-MSCs and alleviated the toxic effects caused by compression. The actin stress fibers was suppressed obviously under compression, and pioglitazone alleviated the adverse outcomes. Pioglitazone exerted protective effects on compression-induced NP-MSCs apoptosis according to annexin V/PI double-staining and TUNEL assays. Pioglitazone suppressed compression-induced NP-MSCs oxidative stress, including decreasing compression-induced overproduction of reactive oxygen species (ROS) and malondialdehyde (MDA), and alleviated compression-induced mitochondrial membrane potential (MMP) decrease. Ultrastructure collapse of the mitochondria exhibited a notable improvement by pioglitazone in compression-induced NP-MSCs according to transmission electron microscopy (TEM). Furthermore, the molecular results showed that pioglitazone significantly decreased the expression of apoptosis-associated proteins, including cyto.cytochrome c, Bax, cleaved caspase-9, and cleaved caspase-3, and promoted Bcl-2 expression. These results indicated that pioglitazone alleviated compression-induced NP-MSCs apoptosis by suppressing oxidative stress and the mitochondrial apoptosis pathway, which may be a valuable candidate for the treatment of IVD degeneration.

scholarly journals Exosomes Derived from Bone Mesenchymal Stem Cells Alleviate Compression-Induced Nucleus Pulposus Cell Apoptosis by Inhibiting Oxidative Stress

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yiqiang Hu ◽  
Ranyang Tao ◽  
Linfang Wang ◽  
Lang Chen ◽  
Ze Lin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Nucleus Pulposus ◽  
Cell Apoptosis ◽  
Nucleus Pulposus Cell ◽  
Inhibitory Effect ◽  
Bone Mesenchymal Stem Cells ◽  
Induced Apoptosis ◽  
Ivd Degeneration

Oxidative stress is relevant in compression-induced nucleus pulposus (NP) cell apoptosis and intervertebral disc (IVD) degeneration. Exosomes derived from bone mesenchymal stem cells (BMSCs-Exos) are key secretory products of MSCs, with important roles in tissue regeneration. This research is aimed at studying the protective impact of BMSCs-Exos on NP cell apoptosis caused by compression and investigating the underlying mechanisms. Our results indicated that we isolated BMSCs successfully. Exosomes were isolated from the BMSCs and found to alleviate the inhibitory effect that compression has on proliferation and viability in NP cells, decreasing the toxic effects of compression-induced NP cells. AnnexinV/PI double staining and TUNEL assays indicated that the BMSCs-Exos reduced compression-induced apoptosis. In addition, our research found that BMSCs-Exos suppressed compression-mediated NP oxidative stress by detecting the ROS and malondialdehyde level. Furthermore, BMSCs-Exos increased the mitochondrial membrane potential and alleviated compression-induced mitochondrial damage. These results indicate that BMSCs-Exos alleviate compression-mediated NP apoptosis by suppressing oxidative stress, which may provide a promising cell-free therapy for treating IVD degeneration.

scholarly journals Injectable Hydrogel Combined with Nucleus Pulposus-Derived Mesenchymal Stem Cells for the Treatment of Degenerative Intervertebral Disc in Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Feng Wang ◽  
Li-ping Nan ◽  
Shi-feng Zhou ◽  
Yang Liu ◽  
Ze-yu Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Rat Model ◽  
Injectable Hydrogel ◽  
Cell Scaffold ◽  
Ivd Degeneration

Stem cell-based tissue engineering in treating intervertebral disc (IVD) degeneration is promising. An appropriate cell scaffold can maintain the viability and function of transplanted cells. Injectable hydrogel has the potential to be an appropriate cell scaffold as it can mimic the condition of the natural extracellular matrix (ECM) of nucleus pulposus (NP) and provide binding sites for cells. This study was aimed at investigating the effect of injectable hydrogel-loaded NP-derived mesenchymal stem cells (NPMSC) for the treatment of IVD degeneration (IDD) in rats. In this study, we selected injectable 3D-RGD peptide-modified polysaccharide hydrogel as a cell transplantation scaffold. In vitro, the biocompatibility, microstructure, and induced differentiation effect on NPMSC of the hydrogel were studied. In vivo, the regenerative effect of hydrogel-loaded NPMSC on degenerated NP in a rat model was evaluated. The results showed that NPMSC was biocompatible and able to induce differentiation in hydrogel in vivo. The disc height index (almost 87%) and MRI index (3313.83±227.79) of the hydrogel-loaded NPMSC group were significantly higher than those of other groups at 8 weeks after injection. Histological staining and immunofluorescence showed that the hydrogel-loaded NPMSC also partly restored the structure and ECM content of degenerated NP after 8 weeks. Moreover, the hydrogel could support long-term NPMSC survival and decrease cell apoptosis rate of the rat IVD. In conclusion, injectable hydrogel-loaded NPMSC transplantation can delay the level of IDD and promote the regeneration of the degenerative IVD in the rat model.

scholarly journals High BMPR2 expression leads to enhanced SMAD1/5/8 signalling and GDF6 responsiveness in human adipose-derived stem cells: implications for stem cell therapies for intervertebral disc degeneration

2020 ◽  
Vol 11 ◽  
pp. 204173142091933 ◽  
Author(s):  
Tom Hodgkinson ◽  
Francis Wignall ◽  
Judith A Hoyland ◽  
Stephen M Richardson
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Multipotent Stem Cells ◽  
Protein Receptor ◽  
Morphogenetic Protein

Stem cell–based regenerative strategies are promising for intervertebral disc degeneration. Stimulation of bone-marrow- and adipose-derived multipotent stem cells with recombinant human growth differentiation factor 6 (rhGDF6) promotes anabolic nucleus pulposus like phenotypes. In comparison to mesenchymal stem cells, adipose-derived multipotent stem cells exhibit greater NP-marker gene expression and proteoglycan-rich matrix production. To understand these response differences, we investigated bone morphogenetic protein receptor profiles in donor-matched human mesenchymal stem cells and adipose-derived multipotent stem cells, determined differences in rhGDF6 signalling and their importance in NP-like differentiation between cell populations. Bone morphogenetic protein receptor expression in mesenchymal stem cells and adipose-derived multipotent stem cells revealed elevated and less variable expression of BMPR2 in adipose-derived multipotent stem cells, which corresponded with increased downstream pathway activation (SMAD1/5/8, ERK1/2). Inhibitor studies demonstrated SMAD1/5/8 signalling was required for rhGDF6-induced nucleus-pulposus-like adipose-derived multipotent stem cell differentiation, while ERK1/2 contributed significantly to critical nucleus pulposus gene expression, aggrecan and type II collagen production. These data inform cell regenerative therapeutic choices for intervertebral disc degeneration regeneration and identify further potential optimisation targets.

scholarly journals The effect of doxycycline and collagenase A on the differentiation of mesenchymal stem cells towards a nucleus pulposus phenotype

2021 ◽  
Author(s):  
Olena Bojchuk
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Nucleus Pulposus ◽  
Symptom Relief ◽  
Negative Effects ◽  
Chondrogenic Medium ◽  
Collagen Formation ◽  
Doxycycline Treatment ◽  
Gene Expression Studies ◽  
Ivd Degeneration

Intervertebral disc (IVD) degeneration costs the healthcare system billions of dollars annually and leads to reduced quality of life. Current treatments are invasive and primarily focus on symptom relief rather than repair. This study aimed to facilitate the development of an injectable therapy using chondrogenically differentiated mesenchymal stem cells (MSCs) in the absence of collagen II deposition. Briefly, pelleted MSCs were cultivated in chondrogenic medium and were supplemented with collagenase A or doxycycline in order to inhibit collagen assembly. Results indicated that collagenase A and doxycycline treatment had no negative effects on DNA or proteoglycan content. Collagenase A at all concentrations affected collagen content, as did doxycycline at low concentrations. Furthermore, preliminary gene expression studies for nucleus pulposus markers showed that collagenase A and doxycycline may have some effect on terminal differentiation of MSCs in chondrogenic medium. Overall, the findings suggest that collagenase A and doxycycline supplementation can be used to inhibit collagen formation, thereby facilitating the further development of an injectable therapy for IVD repair.

scholarly journals The effect of doxycycline and collagenase A on the differentiation of mesenchymal stem cells towards a nucleus pulposus phenotype

2021 ◽  
Author(s):  
Olena Bojchuk
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Nucleus Pulposus ◽  
Symptom Relief ◽  
Negative Effects ◽  
Chondrogenic Medium ◽  
Collagen Formation ◽  
Doxycycline Treatment ◽  
Gene Expression Studies ◽  
Ivd Degeneration

Intervertebral disc (IVD) degeneration costs the healthcare system billions of dollars annually and leads to reduced quality of life. Current treatments are invasive and primarily focus on symptom relief rather than repair. This study aimed to facilitate the development of an injectable therapy using chondrogenically differentiated mesenchymal stem cells (MSCs) in the absence of collagen II deposition. Briefly, pelleted MSCs were cultivated in chondrogenic medium and were supplemented with collagenase A or doxycycline in order to inhibit collagen assembly. Results indicated that collagenase A and doxycycline treatment had no negative effects on DNA or proteoglycan content. Collagenase A at all concentrations affected collagen content, as did doxycycline at low concentrations. Furthermore, preliminary gene expression studies for nucleus pulposus markers showed that collagenase A and doxycycline may have some effect on terminal differentiation of MSCs in chondrogenic medium. Overall, the findings suggest that collagenase A and doxycycline supplementation can be used to inhibit collagen formation, thereby facilitating the further development of an injectable therapy for IVD repair.

scholarly journals Dental Mesenchymal Stem Cell: Its role in tooth development, types, surface antigens and differentiation potential

2017 ◽  
Vol 1 (2) ◽  
pp. 50 ◽  
Author(s):  
Yohanna Feter ◽  
Nadhia Sari Afiana ◽  
Jessica Nathalia Chandra ◽  
Kharima Abdullah ◽  
Jasmine Shafira ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cellular Therapy ◽  
Tooth Development ◽  
Surface Antigens ◽  
Deciduous Teeth ◽  
Dental Tissue ◽  
Differentiation Potential ◽  
Periodontal Ligament Stem Cell

Reciprocal interaction between oral ectodermal epithelial cells and mesenchymal stem cells (MSCs)-derived from the cranial neural crest starts the teeth development. The role of dental MSCs continues throughout life. The dental MSCs do not only play a role in tooth development but also in tooth homeostasis and repair. There are many kinds of dental MSCs, such as dental pulp stem cell (DPSC), stem cell from apical papilla (SCAP), stem cell from exfoliated deciduous teeth (SHED), periodontal ligament stem cell (PDLSC) and stem cell from dental follicle (DFSC). Aligned with the proposed criteria by the International Society for Cellular Therapy (ISCT), dental MSCs are adherent cells and like other MSCs, dental tissue MSCs are capable of giving rise to cell lineages such as osteo/odontogenic, adipogenic, and neurogenic. Various surface antigens of dental MSCs were reported, however, mostly typical antigens suggested by ISCT were fulfilled. Surface antigens from each dental MSCs (DPSC, SCAP, SHED, PDLSC and DFSC) are being described in the current report.Keywords: dental stem cells, mesenchymal stem cells, tissue regeneration, DPSC, SCAP, SHED, PDLSC, DFSC

scholarly journals Mesenchymal Stem Cells Protect Nucleus Pulposus Cells from Compression-Induced Apoptosis by Inhibiting the Mitochondrial Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Sheng Chen ◽  
Lei Zhao ◽  
Xiangyu Deng ◽  
Deyao Shi ◽  
Fashuai Wu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Viability ◽  
Nucleus Pulposus ◽  
Mitochondrial Pathway ◽  
Nucleus Pulposus Cells ◽  
Caspase 9 ◽  
Induced Apoptosis ◽  
Related Proteins ◽  
Cytosolic Cytochrome

Objective. Excessive apoptosis of nucleus pulposus cells (NPCs) induced by various stresses, including compression, contributes to the development of intervertebral disc degeneration (IVDD). Mesenchymal stem cells (MSCs) can benefit the regeneration of NPCs and delay IVDD, but the underlying molecular mechanism is poorly understood. This study aimed to evaluate the antiapoptosis effects of bone marrow-derived MSC (BMSC) on rat NPCs exposed to compression and investigate whether the mitochondrial pathway was involved. Methods. BMSCs and NPCs were cocultured in the compression apparatus at 1.0 MPa for 36 h. Cell viability, apoptosis, mitochondrial function, and the expression of apoptosis-related proteins were evaluated. Results. The results showed that coculturing with BMSCs increased the cell viability and reduced apoptosis of NPCs exposed to compression. Meanwhile, BMSCs could relieve the compression-induced mitochondrial damage of NPCs by decreasing reactive oxygen species level and maintaining mitochondrial membrane potential as well as mitochondrial integrity. Furthermore, coculturing with BMSCs suppressed the activated caspase-3 and activated caspase-9, decreased the expressions of cytosolic cytochrome c and Bax, and increased the expression of Bcl-2. Conclusions. Our results suggest that BMSCs can protect against compression-induced apoptosis of NPCs by inhibiting the mitochondrial pathway and thus enhance our understanding on the MSC-based therapy for IVDD.

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