학술논문

Nutrient supply and nucleus pulposus cell function: effects of the transport properties of the cartilage endplate and potential implications for intradiscal biologic therapy
Document Type
article
Source
Osteoarthritis and Cartilage. 27(6)
Subject
Biomedical and Clinical Sciences
Clinical Sciences
Adult
Aged
Aggrecans
Animals
Biological Transport
Cadaver
Cartilage
Articular
Cattle
Cell Survival
Cell Transplantation
Collagen Type II
Culture Techniques
Diffusion Chambers
Culture
Fluorescence Recovery After Photobleaching
Gene Expression
Genetic Therapy
Humans
Intercellular Signaling Peptides and Proteins
Intervertebral Disc Degeneration
Lumbar Vertebrae
Matrix Metalloproteinase 2
Middle Aged
Nucleus Pulposus
Nutrients
Plant Extracts
Regenerative Medicine
Spectroscopy
Fourier Transform Infrared
Cartilage endplate
Disc degeneration
Fourier transform infrared imaging
Nutrient transport
Nucleus pulposus cell
Low back pain
Biomedical Engineering
Human Movement and Sports Sciences
Arthritis & Rheumatology
Clinical sciences
Sports science and exercise
Language
Abstract
ObjectiveIntradiscal biologic therapy is a promising strategy for managing intervertebral disc degeneration. However, these therapies require a rich nutrient supply, which may be limited by the transport properties of the cartilage endplate (CEP). This study investigated how fluctuations in CEP transport properties impact nutrient diffusion and disc cell survival and function.DesignHuman CEP tissues harvested from six fresh cadaveric lumbar spines (38-66 years old) were placed at the open sides of diffusion chambers. Bovine nucleus pulposus (NP) cells cultured inside the chambers were nourished exclusively by nutrients diffusing through the CEP tissues. After 72 h in culture, depth-dependent NP cell viability and gene expression were measured, and related to CEP transport properties and biochemical composition determined using fluorescence recovery after photobleaching and Fourier transform infrared (FTIR) spectroscopy.ResultsSolute diffusivity varied nearly 4-fold amongst the CEPs studied, and chambers with the least permeable CEPs appeared to have lower aggrecan, collagen-2, and matrix metalloproteinase-2 gene expression, as well as a significantly shorter viable distance from the CEP/nutrient interface. Increasing chamber cell density shortened the viable distance; however, this effect was lost for low-diffusivity CEPs, which suggests that these CEPs may not provide enough nutrient diffusion to satisfy cell demands. Solute diffusivity in the CEP was associated with biochemical composition: low-diffusivity CEPs had greater amounts of collagen and aggrecan, more mineral, and lower cross-link maturity.ConclusionsCEP transport properties dramatically affect NP cell survival/function. Degeneration-related CEP matrix changes could hinder the success of biologic therapies that require increased nutrient supply.