Investigation of the Effect of Secreted Factors from Mesenchymal Stem Cells on Disc Cells from Degenerated Discs

Low back pain is experienced by a large number of people in western countries and may be caused and influenced by many different pathologies and psychosocial factors including disc degeneration. Disc degeneration involves the increased expression of proinflammatory cytokines and matrix metalloproteinases (MMPs) in the disc environment, which leads to the loss of extracellular matrix (ECM) and the viability of the native disc cells (DCs). Treatment approaches using growth factors and cell therapy have been proposed due to the compelling results that growth factors and mesenchymal stem cells (MSCs) can influence the degenerated discs. The aim of this study was to investigate the effects of conditioned media (CM) from human MSCs (hMSCs) and connective tissue growth factor (CTGF) and TGF-β on disc cells, and hMSCs isolated from patients with degenerative discs and severe low back pain. The aim was also to examine the constituents of CM in order to study the peptides that could bring about intervertebral disc (IVD) regeneration. DCs and hMSC pellets (approx.. 200,000 cells) were cultured and stimulated with hMSC-derived CM or CTGF and TGF-β over 28 days. The effects of CM and CTGF on DCs and hMSCs were assessed via cell viability, proteoglycan production, the expression of ECM proteins, and chondrogenesis in 3D pellet culture. To identify the constituents of CM, CM was analyzed with tandem mass spectrometry. The findings indicate that CM enhanced the cellular viability and ECM production of DCs while CTGF and the control exhibited nonsignificant differences. The same was observed in the hMSC group. Mass spectrometry analysis of CM identified >700 peptides, 129 of which showed a relative abundance of ≥2 (CTGF among them). The results suggest that CM holds potential to counter the progression of disc degeneration, likely resulting from the combination of all the substances released by the hMSCs. The soluble factors released belong to different peptide families. The precise mechanism underlying the regenerative effect needs to be investigated further, prior to incorporating peptides in the development of new treatment strategies for low back pain that is potentially caused by IVD degeneration.

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Intervertebral Disc Degeneration and Low Back Pain: Molecular Mechanisms and Stem Cell Therapy

The Indonesian Biomedical Journal ◽

10.18585/inabj.v10i1.426 ◽

2018 ◽

Vol 10 (1) ◽

pp. 1 ◽

Cited By ~ 1

Author(s):

Anna Meiliana ◽

Nurrani Mustika Dewi ◽

Andi Wijaya

Keyword(s):

Stem Cells ◽

Extracellular Matrix ◽

Stem Cell ◽

Low Back Pain ◽

Back Pain ◽

Intervertebral Disc ◽

Nucleus Pulposus ◽

Disc Degeneration ◽

Intervertebral Disc Degeneration ◽

Low Back

BACKGROUND: Low back pain (LBP) mostly caused by disc degeneration, reflects to a tremendous of health care system and economy. More knowledge about these underlying pathologies will improve the opportunities that may represent critical therapeutic targets.CONTENT: Basic research is advancing the understanding of the pathogenesis and management of LBP at the molecular and genetic levels. Cytokines such as matrix metalloproteinases, phospholipase A2, nitric oxide, and tumor necrosis factor-α are thought to contribute to the development of LBP. Mesenchymal stem cells (MSCs) transplant to cartilage-like cells and secrete extracellular matrix and encourage nucleus pulposus (NP) cell activity inhibiting NP cell apoptosis, together with some chemical mediators such as cytokines and growth factors become a safe and effective new strategy for intervertebral disc degeneration (IDD) treatment and regeneration.SUMMARY: IDD occurs where there is a loss of homeostatic balance with a predominantly catabolic metabolic profile. A basic understanding of the molecular changes occurring in the degenerating disc is important for practicing clinicians to help them to inform patients to alter lifestyle choices, identify beneficial or harmful supplements, or offer new biologic, genetic, or stem cell therapies.KEYWORDS: low back pain (LBP), intervertebral disc (IVD), degeneration, nucleus pulposus (NP), annulus fibrosus (AF), extracellular matrix (ECM), genetic, stem cells

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Correction to: BMP-3 Promotes Matrix Production in Co-cultured Stem Cells and Disc Cells from Low Back Pain Patients by Hingert D, Barreto Henriksson H, Baranto A, and Brisby H. Tissue Eng Part A 2019;26(1–2):47–56. DOI: 10.1089/ten.tea.2019.0125

Tissue Engineering Part A ◽

10.1089/ten.tea.2019.0125.correx ◽

2020 ◽

Vol 26 (5-6) ◽

pp. 373-373

Keyword(s):

Stem Cells ◽

Low Back Pain ◽

Back Pain ◽

Low Back ◽

Disc Cells ◽

Matrix Production ◽

Pain Patients

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BMP-3 Promotes Matrix Production in Co-cultured Stem Cells and Disc Cells from Low Back Pain Patients

Tissue Engineering Part A ◽

10.1089/ten.tea.2019.0125 ◽

2020 ◽

Vol 26 (1-2) ◽

pp. 47-56

Author(s):

Daphne Hingert ◽

Helena Barreto Henriksson ◽

Adad Baranto ◽

Helena Brisby

Keyword(s):

Stem Cells ◽

Low Back Pain ◽

Back Pain ◽

Low Back ◽

Disc Cells ◽

Matrix Production ◽

Pain Patients

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Pathological Effects of Cortisol on Intervertebral Disc Cells and Mesenchymal Stem Cells from Lower Back Pain Patients

Cells Tissues Organs ◽

10.1159/000500772 ◽

2019 ◽

Vol 207 (1) ◽

pp. 34-45 ◽

Cited By ~ 2

Author(s):

Daphne Hingert ◽

Johanna Nilsson ◽

Helena Barreto Henriksson ◽

Adad Baranto ◽

Helena Brisby

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Back Pain ◽

Disc Degeneration ◽

Lower Back Pain ◽

Cell Types ◽

The Body ◽

Lower Back ◽

Induced Stress ◽

Disc Cells

In western countries, lower back pain (LBP) is one of the most common disorders, experienced by more than 80% of the population. Chronic LBP due to disc degeneration has been linked to ongoing inflammatory processes in the disc and endplates. Pain effects the body in different ways, inducing a general stress response in which the body responds by releasing the stress hormone cortisol. Little is known about the impact of pain-induced stress on the progression of disc degeneration. Thus, the effects of cortisol on disc cells (DCs) and human mesenchymal stem cells (hMSCs) were explored in vitro with the objective of investigating the repercussions of cortisol on these cell types involved in de- and regenerative mechanisms of the disc. DC and hMSC pellet cultures were exposed to cortisol at two concentrations (150 and 300 ng/mL) for 28 days to simulate pain-induced stress. Cell viability, histological staining, and GAG DNA, along with apoptotic assays were conducted. Detection of OCT4, SOX9, IL-1R, and CXCR2 expressions was performed by immunohistochemistry. With cortisol treatment, restricted cell proliferation and less GAG production in both DCs and hMSCs were observed. Suppression of the differentiation and immunomodulatory efficacy of hMSCs was also detected. Moreover, elevated expressions of IL-1R and CXCR2 were detected in both cell types. To conclude, constant exposure to cortisol even at a physiological level enhanced pathological cellular processes in both DCs and hMSCs, which further jeopardized chondrogenesis. This suggests that cortisol resulting from pain-induced stress is a contributing component of intervertebral disc degeneration and may negatively affect regenerative attempts of the disc.

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Human Umbilical Cord Mesenchymal Stem Cell Transplantation for the Treatment of Chronic Discogenic Low Back Pain

January 2018 - Pain Physician ◽

10.36076/ppj.2014/17/e525 ◽

2014 ◽

Vol 4;17 (4;7) ◽

pp. E525-E530 ◽

Cited By ~ 6

Author(s):

Baogan Peng

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Low Back Pain ◽

Back Pain ◽

Umbilical Cord ◽

Chronic Low Back Pain ◽

Human Umbilical Cord ◽

Low Back ◽

Surgical Fusion ◽

Discogenic Low Back Pain

Background: Chronic low back pain is one of the major causes of disability and thus has a major socioeconomic impact. Intervertebral disc degeneration is the main cause of chronic low back pain. Treatment for chronic discogenic low back pain has traditionally been limited to either conservative management or surgical fusion. If conservative treatment fails, then surgical fusion is commonly considered. Current treatments are limited to treat the symptoms and not the underlying biologic alterations of the disc. Objective: Human umbilical cord tissue-derived mesenchymal stem cells (HUC-MSCs) contain stem cells and possess the ability to regenerate degenerative discs. Based on the results of previous in vitro and animal experiments, we conducted a preliminary study to test the feasibility and safety and to obtain an early indication for the therapeutic value of HUC-MSC transplantation in patients with chronic discogenic low back pain. Study Design: This is the first study involving treatment of chronic low back pain using HUCMSC transplantation. Setting: The study was performed at a spine center in China. Methods: Two patients with chronic discogenic low back pain were treated with HUC-MSC transplantation. An 11-point visual analog scale (VAS, 0 – 10) and Oswestry Disability Index (ODI, 0 – 100) were used to assess the back pain symptoms and the lumbar function, respectively. Results: After transplantation, the pain and function improved immediately in the 2 patients. The VAS and ODI scores decreased obviously during a 2-year follow-up period. Limitations: The shortcoming of this study is that it is a preliminary study with only 2 patients. Conclusion: The clinical outcomes indicated that HUC-MSC transplantation is a favorable alternative method for the treatment of chronic discogenic low back pain. Key words: Intervertebral disc degeneration, discogenic low back pain, chronic low back pain, lumbar discography, mesenchymal stem cells, human umbilical cord mesenchymal stem cells, transplantation

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