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Biomaterials-Induced Stem Cells Specific Differentiation Into Intervertebral Disc Lineage Cells.

ABSTRACT: Stem cell therapy, which promotes stem cells differentiation toward specialized cell types, increases the resident population and production of extracellular matrix, and can be used to achieve intervertebral disc (IVD) repair, has drawn great attention for the development of IVD-regenerating materials. Many materials that have been reported in IVD repair have the ability to promote stem cells differentiation. However, due to the limitations of mechanical properties, immunogenicity and uncontrollable deviations in the induction of stem cells differentiation, there are few materials that can currently be translated into clinical applications. In addition to the favorable mechanical properties and biocompatibility of IVD materials, maintaining stem cells activity in the local niche and increasing the ability of stem cells to differentiate into nucleus pulposus (NP) and annulus fibrosus (AF) cells are the basis for promoting the application of IVD-regenerating materials in clinical practice. The purpose of this review is to summarize IVD-regenerating materials that focus on stem cells strategies, analyze the properties of these materials that affect the differentiation of stem cells into IVD-like cells, and then present the limitations of currently used disc materials in the field of stem cell therapy and future research perspectives.

SUBMITTER: Peng Y

PROVIDER: S-EPMC7019859 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Biomaterials-Induced Stem Cells Specific Differentiation Into Intervertebral Disc Lineage Cells.

Peng Yizhong Y Huang Donghua D Liu Sheng S Li Jinye J Qing Xiangcheng X Shao Zengwu Z

Frontiers in bioengineering and biotechnology 20200207

Stem cell therapy, which promotes stem cells differentiation toward specialized cell types, increases the resident population and production of extracellular matrix, and can be used to achieve intervertebral disc (IVD) repair, has drawn great attention for the development of IVD-regenerating materials. Many materials that have been reported in IVD repair have the ability to promote stem cells differentiation. However, due to the limitations of mechanical properties, immunogenicity and uncontroll ...[more]

PMID: 32117935

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Project description:IntroductionAbnormal biomechanics plays a role in intervertebral disc degeneration. Adipose-derived stromal cells (ADSCs) have been implicated in disc integrity; however, their role in the setting of mechanical stimuli upon the disc's nucleus pulposus (NP) remains unknown. As such, the present study aimed to evaluate the influence of ADSCs upon NP cells in compressive load culture.MethodsHuman NP cells were cultured in compressive load at 3.0MPa for 48 hours with or without ADSCs co-culture (the ratio was 50:50). We used flow cytometry, live/dead staining and scanning electron microscopy (SEM) to evaluate cell death, and determined the expression of specific apoptotic pathways by characterizing the expression of activated caspases-3, -8 and -9. We further used real-time (RT-) PCR and immunostaining to determine the expression of the extracellular matrix (ECM), mediators of matrix degradation (e.g. MMPs, TIMPs and ADAMTSs), pro-inflammatory factors and NP cell phenotype markers.ResultsADSCs inhibited human NP cell apoptosis via suppression of activated caspase-9 and caspase-3. Furthermore, ADSCs protected NP cells from the degradative effects of compressive load by significantly up-regulating the expression of ECM genes (SOX9, COL2A1 and ACAN), tissue inhibitors of metalloproteinases (TIMPs) genes (TIMP-1 and TIMP-2) and cytokeratin 8 (CK8) protein expression. Alternatively, ADSCs showed protective effect by inhibiting compressive load mediated increase of matrix metalloproteinases (MMPs; MMP-3 and MMP-13), disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs; ADAMTS-1 and 5), and pro-inflammatory factors (IL-1beta, IL-6, TGF-beta1 and TNF-alpha).ConclusionsOur study is the first in vitro study assessing the impact of ADSCs on NP cells in an un-physiological mechanical stimulation culture environment. Our study noted that ADSCs protect compressive load induced NP cell death and degradation by inhibition of activated caspase-9 and -3 activity; regulating ECM and modulator genes, suppressing pro-inflammatory factors and preserving CK8. Consequently, the protective impact of ADSCs found in this study provides an essential understanding and expands our knowledge as to the utility of ADSCs therapy for intervertebral disc regeneration.

Dataset Information

Biomaterials-Induced Stem Cells Specific Differentiation Into Intervertebral Disc Lineage Cells.

Publications

Biomaterials-Induced Stem Cells Specific Differentiation Into Intervertebral Disc Lineage Cells.

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