scholarly journals Cartilage Endplate Stem Cells Transdifferentiate Into Nucleus Pulposus Cells via Autocrine Exosomes

2021 ◽  
Vol 9 ◽  
Author(s):  
Liwen Luo ◽  
Junfeng Gong ◽  
Hongyu Zhang ◽  
Jinghao Qin ◽  
Changqing Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wnt Signaling ◽  
Nucleus Pulposus ◽  
High Speed ◽  
Wnt Pathway ◽  
Transforming Growth Factor ◽  
Hypoxia Inducible Factor ◽  
Enrichment Analysis ◽  
Nucleus Pulposus Cells ◽  
Cartilage Endplate

Stem cells derived from cartilage endplate (CEP) cells (CESCs) repair intervertebral disc (IVD) injury; however, the mechanism remains unclear. Here, we evaluated whether CESCs could transdifferentiate into nucleus pulposus cells (NPCs) via autocrine exosomes and subsequently inhibit IVD degeneration. Exosomes derived from CESCs (CESC-Exos) were extracted and identified by ultra-high-speed centrifugation and transmission electron microscopy. The effects of exosomes on the invasion, migration, and differentiation of CESCs were assessed. The exosome-activating hypoxia-inducible factor (HIF)-1α/Wnt pathway was investigated using lenti-HIF-1α and Wnt agonists/inhibitors in cells and gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis in normal and degenerated human CEP tissue. The effects of GATA binding protein 4 (GATA4) on transforming growth factor (TGF)-β expression and on the invasion, migration, and transdifferentiation of CESCs were investigated using lenti-GATA4, TGF-β agonists, and inhibitors. Additionally, IVD repair was investigated by injecting CESCs overexpressing GATA4 into rats. The results indicated that CESC-Exos promoted the invasion, migration, and differentiation of CESCs by autocrine exosomes via the HIF-1α/Wnt pathway. Additionally, increased HIF-1α enhanced the activation of Wnt signaling and activated GATA4 expression. GATA4 effectively promoted TGF-β secretion and enhanced the invasion, migration, and transdifferentiation of CESCs into NPCs, resulting in promotion of rat IVD repair. CESCs were also converted into NPCs as endplate degeneration progressed in human samples. Overall, we found that CESC-Exos activated HIF-1α/Wnt signaling via autocrine mechanisms to increase the expression of GATA4 and TGF-β1, thereby promoting the migration of CESCs into the IVD and the transformation of CESCs into NPCs and inhibiting IVDD.

scholarly journals Bi-Directional Exchange of Membrane Components Occurs during Co-Culture of Mesenchymal Stem Cells and Nucleus Pulposus Cells

PLoS ONE ◽  
2012 ◽  
Vol 7 (3) ◽  
pp. e33739 ◽  
Author(s):  
Sandra Strassburg ◽  
Nigel W. Hodson ◽  
Patrick I. Hill ◽  
Stephen M. Richardson ◽  
Judith A. Hoyland
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Nucleus Pulposus ◽  
Nucleus Pulposus Cells ◽  
Membrane Components

Chemically Defined Medium With TGF-β3 Enhances Matrix Elaboration by Nucleus Pulposus Cells Encapsulated in Novel Photocrosslinked Carboxymethylcellulose Hydrogels

2009 ◽  
Author(s):  
Anna T. Reza ◽  
Steven B. Nicoll
Keyword(s):  
Nucleus Pulposus ◽  
Transforming Growth Factor Beta ◽  
Structural Integrity ◽  
Transforming Growth Factor ◽  
Swelling Pressure ◽  
Type Ii Collagen ◽  
Defined Medium ◽  
Nucleus Pulposus Cells ◽  
Phenotypic Properties ◽  
Medium Formulation

Back pain is a significant clinical concern often attributed to degeneration of the intervertebral disc (IVD) and the associated dehydration of the nucleus pulposus (NP) [1]. The NP is a gel-like tissue at the center of the disc, rich in proteoglycans and type II collagen that functions to resist compressive forces through the generation of a hydrostatic swelling pressure [2]. Tissue engineering strategies may provide a viable NP replacement therapy as an alternative to current surgical procedures. However, several factors including medium formulation and scaffold selection can affect construct maturation [3]. For example, transforming growth factor-beta 3 (TGF-β3) has been shown to enhance the functional properties of tissue engineered cartilage constructs, with more pronounced results observed in serum-free conditions [3]. NP cells are commonly cultured in ionically crosslinked alginate hydrogels to maintain their phenotypic properties; however, these scaffolds have been shown to lose structural integrity over time, creating a need for an alternative biomaterial [4]. Therefore, the objective of this study was to examine the effects of medium formulation on NP cells encapsulated in novel photocrosslinked carboxymethylcellulose (CMC) hydrogels.

scholarly journals Intraperitoneal administration of mesenchymal stem cells is effective at mitigating detrusor deterioration after pBOO

2020 ◽  
Vol 318 (3) ◽  
pp. F549-F556 ◽  
Author(s):  
Bridget Wiafe ◽  
Rutuja Kadam ◽  
Peter D. Metcalfe
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Intravenous Administration ◽  
Transforming Growth Factor ◽  
Mammalian Target Of Rapamycin ◽  
Hypoxia Inducible Factor ◽  
Intraperitoneal Administration ◽  
Outlet Obstruction ◽  
Systemic Exposure ◽  
Transforming Growth Factor Β

Partial bladder outlet obstruction (pBOO) results in bladder fibrosis that is initiated by an inflammatory cascade and the decompensation after smooth muscle hypertrophy. We have been using an animal model to develop the hypothesis that mesenchymal stem cells (MSCs) are able to mitigate this cytokine cascade and prevent bladder deterioration. We hypothesized that intraperitoneal administration of MSCs can produce the same effects as intravenously administered cells but may require higher dosing. Intraperitoneal treatment will provide insights into the mechanisms of action and may offer advantages over intravenous administration, as it will permit allow higher doses and potentially reduce systemic exposure. Rats underwent a surgical induction of pBOO and instillation of either 1 × 106 or 5 × 106 commercially acquired MSCs into the peritoneum. RT-PCR, immunohistochemistry, and urodynamics were used to compare treatment groups with controls. pBOO resulted in a marked, statistically significant, upregulation of inflammatory markers in the bladder, including transforming growth factor-β, hypoxia-inducible factor-1α, hypoxia-inducible factor-3α, mammalian target of rapamycin, and collagen types I and III. Moderate but inconsistent levels of downregulation were seen with 1 × 106 MSCs, but excellent and reliable downregulation was seen with 5 × 106 MSCs ( P < 0.05). Immunohistochemistry confirmed that protein levels were affected in accordance with mRNA upregulation. Urodynamics demonstrated MSC treatment resulted in whole organ physiological benefits, as they prevented elevations in detrusor pressure. In conclusion, intraperitoneal administration of MSCs resulted in a similar effect as intravenous administration; however, this required a higher dose. This has significant implications for determining the mechanism of action and potential clinical application for human therapy.

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