Abstract
SummaryBackgroundLumbar intervertebral disc (IVD) herniations are associated with significant disability. Discectomy is the conventional treatment option for IVD herniations but causes a defect in the IVD, which has low self-repair ability, thereby representing a risk of further IVD degeneration. An acellular, bioresorbable, and good manufacturing practice (GMP)-compliant in situ-forming gel, which corrects discectomy-associated IVD defects and prevents further IVD degeneration had been developed. However, this acellular matrix-based strategy has certain limitations, particularly in elderly patients, whose tissues have low self-repair ability. The aim of this study was to investigate the therapeutic efficacy of using a combination of newly-developed, ultra-purified, GMP-compliant, human bone marrow mesenchymal stem cells (rapidly expanding clones; RECs) and the gel for IVD regeneration after discectomy in a sheep model of severe IVD degeneration.MethodsRECs and nucleus pulposus cells (NPCs) were co-cultured in the gel. In addition, RECs combined with the gel were implanted into IVDs following discectomy in sheep with degenerated IVDs.FindingsGene expression of NPC markers, growth factors, and extracellular matrix increased significantly in the co-culture compared to that in each mono-culture. The REC and gel combination enhanced IVD regeneration after discectomy (up to 24 weeks) in the severe IVD degeneration sheep model.InterpretationThese findings demonstrate the translational potential of the combination of RECs with an in situ-forming gel for the treatment of herniations in degenerative human IVDs.FundingMinistry of Education, Culture, Sports, Science, and Technology of Japan, Japan Agency for Medical Research and Development, and the Mochida Pharmaceutical Co., Ltd.
Highlights
Lumbar intervertebral disc (IVD) herniations, which can cause sciatica, are associated with significant disability and a decreased quality of life.[1]
The present study demonstrates that the expression levels of nucleus pulposus cell (NPC) markers, growth factors, and extracellular matrix components were significantly increased in the co-culture of human nucleus pulposus cells (NPCs) and RECs compared with those observed in the co-culture of NPCs with commercially available bone-derived mesenchymal stem cells (BMSCs)
The findings reveal that the combination of ultra-purified BMSCs in the form of RECs and in situ-forming gel enhances IVD regeneration after discectomy in a sheep model exhibiting severe IVD degeneration, without resulting in neoplastic changes, and enable the maintenance of mechanical functions after implantation
Summary
Lumbar intervertebral disc (IVD) herniations, which can cause sciatica, are associated with significant disability and a decreased quality of life.[1] Discectomy is the conventional surgical procedure involving the removal of www.thelancet.com Vol 76 Month February, 2022. Discectomy is the conventional surgical procedure involving the removal of intervertebral disc (IVD) materials compressing the nerve root. BMSCs used for clinical studies often lead to variable or even contradictory findings because these BMSCs always include nondifferentiating contaminant cells. To overcome these limitations, we developed genetically stable, ultra-purified, clonogenic BMSCs (known as rapidly expanding clones; RECs) that exhibited all the functions of BMSCs and did not show lot-related differences in clinical applications
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