Combination of ultra-purified stem cells with an in situ-forming bioresorbable gel enhances intervertebral disc regeneration
| Autor: | Daisuke Ukeba, Katsuhisa Yamada, Takashi Suyama, Darren R. Lebl, Takeru Tsujimoto, Takayuki Nonoyama, Hirokazu Sugino, Norimasa Iwasaki, Masatoki Watanabe, Yumi Matsuzaki, Hideki Sudo |
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| Rok vydání: | 2021 |
| Předmět: |
musculoskeletal diseases
Intervertebral disc regeneration Medicine (General) Sheep Stem Cells General Medicine Intervertebral Disc Degeneration musculoskeletal system General Biochemistry Genetics and Molecular Biology R5-920 Ultra-purified clonogenic bone marrow-derived mesenchymal stem cell Absorbable Implants Medicine Animals Humans In situ-forming gel Intervertebral Disc Combined lumbar canal stenosis Lumbar intervertebral disc herniation Aged Diskectomy |
| Zdroj: | EBioMedicine, Vol 76, Iss, Pp 103845-(2022) |
| ISSN: | 2352-3964 |
| Popis: | Summary: 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. |
| Databáze: | OpenAIRE |
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