Dataset Information

Stem Cells and Intervertebral Disc Regeneration Overview-What They Can and Can't Do.

ABSTRACT:

Background

Low back pain (LPB) is the main cause of disability worldwide with enormous socioeconomic burdens. A major cause of LBP is intervertebral disc degeneration (IDD): a chronic, progressive process associated with exhaustion of the resident cell population, tissue inflammation, degradation of the extracellular matrix and dehydration of the nucleus pulposus. Eventually, IDD may lead to serious sequelae including chronic LBP, disc herniation, segmental instability, and spinal stenosis, which may require invasive surgical interventions. However, no treatment is actually able to directly tackle IDD and hamper the degenerative process. In the last decade, the intradiscal injection of stem cells is raising as a promising approach to regenerate the intervertebral disc. This review aims to describe the rationale behind a regenerative stem cell therapy for IDD as well as the effect of stem cells following their implantation in the disc environment according to preclinical studies. Furthermore, actual clinical evidence and ongoing trials will be discussed, taking into account the future perspective and current limitations of this cutting-edge therapy.

Methods

A literature analysis was performed for this narrative review. A database search of PubMed, Scopus and ClinicalTrials.gov was conducted using "stem cells" combined with "intervertebral disc", "degeneration" and "regeneration" without exclusion based on publication date. Articles were firstly screened on a title-abstract basis and, subsequently, full-text were reviewed. Both preclinical and clinical studies have been included.

Results

The database search yielded recent publications from which the narrative review was completed.

Conclusions

Based on available evidence, intradiscal stem cell therapy has provided encouraging results in terms of regenerative effects and reduction of LBP. However, multicenter, prospective randomized trials are needed in order confirm the safety, efficacy and applicability of such a promising treatment.

SUBMITTER: Vadala G

PROVIDER: S-EPMC8092931 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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.