Combination of ultra-purified stem cells with an in situ-forming bioresorbable gel enhances intervertebral disc regeneration.

EBioMedicine

Department of Orthopedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan; Department of Advanced Medicine for Spine and Spinal Cord Disorders, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N15W7, Sapporo, Hokkaido 060-8638, Japan. Electronic address:

Published: February 2022

AI Article Synopsis

  • Lumbar intervertebral disc (IVD) herniations lead to significant disability, and traditional treatments like discectomy can worsen IVD degeneration due to low self-repair abilities.
  • A new study investigated the use of a bioresorbable gel combined with human bone marrow mesenchymal stem cells (RECs) for IVD regeneration after discectomy in a sheep model.
  • Results showed that the combination therapy significantly improved gene expression linked to IVD regeneration and suggests potential for treating degenerative IVD herniations in humans.

Article Abstract

Background: Lumbar 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.

Methods: RECs 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.

Findings: Gene 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.

Interpretation: These 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.

Funding: Ministry of Education, Culture, Sports, Science, and Technology of Japan, Japan Agency for Medical Research and Development, and the Mochida Pharmaceutical Co., Ltd.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8801983PMC
http://dx.doi.org/10.1016/j.ebiom.2022.103845DOI Listing

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