ArticleTissue engineering. Part A2014
Link N and mesenchymal stem cells can induce regeneration of the early degenerate intervertebral disc.
Article in Tissue engineering. Part A, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 50 citations in OpenAlex.
- Proteolytic enzyme models as tunable preclinical platforms for investigating intervertebral disc degeneration.Frontiers in cell and developmental biology · 2025Review
- Identification of Potential Targets for EGFR-Regulated Nucleus Pulposus Degeneration Using Single-Cell RNA Sequencing and Machine Learning.Journal of inflammation research · 2025Article
- Current Therapeutic Strategies of Intervertebral Disc Regenerative Medicine.Molecular diagnosis & therapy · 2024Review
- Injectable biomaterial induces regeneration of the intervertebral disc in a caprine loaded disc culture model.Biomaterials science · 2023Article
- Review
- Cell sources proposed for nucleus pulposus regeneration.JOR spine · 2021Review
- Article
- Single-Cell RNA-Seq Analysis Reveals Macrophage Involved in the Progression of Human Intervertebral Disc Degeneration.Frontiers in cell and developmental biology · 2021Article
- Intervertebral Disc Repair: Current Concepts.Global spine journal · 2020Article
- Exogenous Delivery of Link N mRNA into Chondrocytes and MSCs-The Potential Role in Increasing Anabolic Response.International journal of molecular sciences · 2019Article
- Human iPSCs can be differentiated into notochordal cells that reduce intervertebral disc degeneration in a porcine model.Theranostics · 2019Article
- Article
- Short Link N promotes disc repair in a rabbit model of disc degeneration.Arthritis research & therapy · 2018Article
- Understanding the molecular biology of intervertebral disc degeneration and potential gene therapy strategies for regeneration: a review.Gene therapy · 2018Review
- Link N as a therapeutic agent for discogenic pain.JOR spine · 2018Article
- Link protein N-terminal peptide and fullerol promote matrix production and decrease degradation enzymes in rabbit annulus cells.Connective tissue research · 2018Article
- Toll-like Receptor Activation Induces Degeneration of Human Intervertebral Discs.Scientific reports · 2017Article
- Infusion of umbilical cord mesenchymal stem cells alleviates symptoms of ankylosing spondylitis.Experimental and therapeutic medicine · 2017Article
- A Histopathological Scheme for the Quantitative Scoring of Intervertebral Disc Degeneration and the Therapeutic Utility of Adult Mesenchymal Stem Cells for Intervertebral Disc Regeneration.International journal of molecular sciences · 2017Article
- Intervertebral disc response to stem cell treatment is conditioned by disc state and cell carrier: AnJournal of orthopaedic translation · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Link N is a naturally occurring peptide that can stimulate proteoglycan synthesis in intervertebral disc (IVD) cells. IVD repair can also potentially be enhanced by mesenchymal stem cell (MSC) supplementation to maximize extracellular matrix (ECM) production. In a previous study, we have shown that Link N can inhibit osteogenesis and increase the chondrogenesis of MSCs in vitro. The aim of the present study was to determine the potential of MSCs and Link N alone or in combination with regard to tissue repair in the degenerate disc. Bovine IVDs with trypsin-induced degeneration were treated with MSCs, Link N, or a combination of MSCs and Link N. Trypsin-treated discs were also injected with phosphate-buffered saline to serve as a degeneration control. The ECM proteins and proteoglycans were extracted from the inner nucleus pulposus (NP) of the discs, and sulfated glycosaminoglycans (GAGs) were analyzed by the dimethyl methylene blue dye-binding assay. The expression of type II collagen was analyzed by western blot. To track the MSCs after injection, MSCs were labeled with PKH67 and observed under confocal microscopy after the 2 week culture period. The GAG content significantly increased compared with the degeneration control when degenerate discs were treated with MSCs, Link N, or a combination of both Link N and MSCs. Histological analysis revealed that the newly synthesized proteoglycan was able to diffuse throughout the ECM and restore tissue content even in areas remote from the cells. The quantity of extractable type II collagen was also increased when the degenerate discs were treated with MSCs and Link N, either alone or together. MSCs survived, integrated in the tissue, and were found distributed throughout the NP after the 2 week culture period. MSCs and Link N can restore GAG content in degenerate discs, when administered separately or together. Treatment with MSCs and Link N can also increase the expression of type II collagen. The results support the concept that biological repair of disc degeneration is feasible, and that the administration of either MSCs or Link N has therapeutic potential in early stages of the disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.