In Vitro Study on Interaction Between Human Nucleus Pulposus Cells and Mesenchymal Stem Cells Through Paracrine Stimulation

Yang, Shuai; Wu, Chang; Shih, Tiffany Ting-Fang; Sun, Yuan-Hui; Lin, Feng-Huei

doi:10.1097/brs.0b013e31817e6974

Cited by 85 publications

(72 citation statements)

References 51 publications

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“…Other researchers have also reported on the stimulatory effect of human NP cells with co-culture with MSCs. Yang et al (2008) showed an increase in cell proliferation, while Le Visage et al (2006) reported an increase in GAG production in a pellet co-culture system. Furthermore, Vadalà et al (2008) showed increased NP cell gene expression of collagen II after cell-matrix-cell co-culture with MSCs.…”

Section: Discussionmentioning

confidence: 99%

Intervertebral disc repair with activated nucleus pulposus cell transplantation: a three-year, prospective clinical study of its safety

Mochida

Sakai²,

Nakamura³

et al. 2015

eCM

111

118

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Degeneration of the lumbar intervertebral discs is irreversible, with no treatment currently available.Building upon experimental studies that demonstrated the importance of the nucleus pulposus (NP) in preserving disc structure, we demonstrated that reinsertion of NP cells slowed further disc degeneration and that direct cell-tocell contact co-culture with mesenchymal stromal cells (MSCs) significantly upregulated the viability of NP cells in basic and pre-clinical studies in vitro and in vivo using animal models and human cells. Here, we report a 3-year result of a prospective clinical study, aimed to assess the safety and efficacy of activated NP cell transplantation in the degenerate lumbar intervertebral disc. Candidates were 9 patients aged 20-29 years who had Pfirrmann's grade III disc degeneration at the level adjacent to the level scheduled for posterior lumbar intervertebral fusion. Viable NP cells from the fused disc were co-cultured in direct contact with autologous bone marrow-derived MSCs. One million activated NP cells were transplanted into the degenerated disc adjacent to the fused level at 7 d after the first fusion surgery. No adverse effects were observed during the 3-year follow-up period. Magnetic resonance imaging did not show any detrimental effects to the transplanted discs and revealed a mild improvement in 1 case. No cases reported any low back pain. Our clinical study confirmed the safety of activated NP cell transplantation, and the findings suggest the minimal efficacy of this treatment to slow the further degeneration of human intervertebral discs.

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Section: Discussionmentioning

confidence: 99%

Intervertebral disc repair with activated nucleus pulposus cell transplantation: a three-year, prospective clinical study of its safety

Mochida

Sakai²,

Nakamura³

et al. 2015

eCM

111

118

View full text Add to dashboard Cite

show abstract

“…The increase of mRNA of the NP marker genes COL2A1, COL6A2, ACAN and SOX9 has been reported as the main result of direct co-culture of human NPCs and MSCs (6). Indirect co-culturing of NPCs and MSCs in the insert system promoted COL2A1 expression in the MSCs and the proliferation of NPCs as well as the expression of ACAN (7). A study of human MSCs that were co-cultured with NP revealed higher expression of COL2A1 and ACAN (8).…”

Section: Introductionmentioning

confidence: 99%

Co-culture of human nucleus pulposus cells with multipotent mesenchymal stromal cells from human bone marrow reveals formation of tunnelling nanotubes

Lehmann

Filipiak

Juzwa

et al. 2013

Molecular Medicine Reports

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Abstract. Degeneration of the intervertebral disc (IVD) is the main cause of age-related damage of spinal tissues. Using multipotent mesenchymal stromal cells (MSCs) regenerative medicine intends to restore the IVD components of annulus fibrosus (AF) and nucleus pulposus (NP). In the present study NP cells (NPCs) and MSCs obtained from adolescent patients suffering from scoliosis were used. IVDs and vertebrae were obtained during surgery and subsequently processed in order to establish cultures of NPCs and MSCs. The two cell types were co-cultured in 1-µm pore size insert system (indirect co-culture) or on one surface (direct co-culture). Prior to co-culture in these systems one of the cell types was stained by lipophilic fluorescent dye DiD (red). The results demonstrated that regardless of the cell type, the flow of DiD from stained to non-stained cells was more efficient in the direct co-culture in comparison with the insert system. Moreover, in the direct system the DiD flow was more efficient from MSCs towards NPCs compared with that in the opposite direction. These data indicated that the membrane interchange between the two cell types was asymmetric. To discriminate the subpopulation of cells that underwent membrane interchange, cells were double stained with DiD and DiO (green). In the first part of the experiment NPCs were stained by DiO and MSCs by DiD. In the second, NPCs were stained by DiD and MSCs by DiO. The cells were co-cultured in the direct system for 8 days and subsequently analyzed by flow cytometry and confocal microscopy.This analysis revealed that >50% of cells were stained by the DiO and DiD dyes. NPCs and MSCs formed structures similar to tunnelling nanotubes (TnT). In conclusion, the formation of TnT-like structures is able to promote, phenotypic changes during the direct co-culture of NPCs with MSCs.

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“…Co-culture of MSC with NP cells stimulates both NP cells proliferation and MSC differentiation toward the chondrogenic lineage. (200)(201)(202)(203) Increased production of cytokines, particularly TGF-b favors these transformations. (203)(204)(205) The NP contains MSC that are similar to the MSC recovered from bone marrow (206), and studies in animal models of DD have shown that MSC injected in the NP area not only survive for months but also proliferate in canine (207,208), porcine (209), and rabbit models (210).…”

Section: Lbp Pathophysiologymentioning

confidence: 99%

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

2018

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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 Abstract R E V I E W A R T I C L Einhibiting 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.

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In Vitro Study on Interaction Between Human Nucleus Pulposus Cells and Mesenchymal Stem Cells Through Paracrine Stimulation

Cited by 85 publications

References 51 publications

Intervertebral disc repair with activated nucleus pulposus cell transplantation: a three-year, prospective clinical study of its safety

Intervertebral disc repair with activated nucleus pulposus cell transplantation: a three-year, prospective clinical study of its safety

Co-culture of human nucleus pulposus cells with multipotent mesenchymal stromal cells from human bone marrow reveals formation of tunnelling nanotubes

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

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