Bone Marrow Aspirate Concentrate Combined with Ultra-Purified Alginate Bioresorbable Gel Enhances Intervertebral Disc Repair in a Canine Model: A Preclinical Proof-of-Concept Study

Author:

Ukeba Daisuke1ORCID,Ishikawa Yoko1,Yamada Katsuhisa1ORCID,Ohnishi Takashi1ORCID,Tachi Hiroyuki1,Tha Khin Khin2ORCID,Iwasaki Norimasa1ORCID,Sudo Hideki1ORCID

Affiliation:

1. Department of Orthopedic Surgery, Hokkaido University Hospital, N14W5, Sapporo, Hokkaido 060-8638, Japan

2. Laboratory for Biomarker Imaging Science, Graduate School of Biomedical Science and Engineering, Hokkaido University, N15 W7, Kita-ku, Sapporo 060-8638, Japan

Abstract

Although discectomy is commonly performed for lumbar intervertebral disc (IVD) herniation, the capacity for tissue repair after surgery is limited, resulting in residual lower back pain, recurrence of IVD herniation, and progression of IVD degeneration. Cell-based therapies, as one-step procedures, are desirable for enhancing IVD repair. This study aimed to investigate the therapeutic efficacy of a combination of newly developed ultra-purified alginate (UPAL) gel and bone marrow aspirate concentrate (BMAC) implantation for IVD repair after discectomy. Prior to an in vivo study, the cell concentration abilities of three commercially available preparation kits for creating the BMAC were compared by measuring the number of bone marrow mesenchymal stem cells harvested from the bone marrow of rabbits. Subsequently, canine-derived BMAC was tested in a canine model using a kit which had the highest concentration rate. At 24 weeks after implantation, we evaluated the changes in the magnetic resonance imaging (MRI) signals as well as histological degeneration grade and immunohistochemical analysis results for type II and type I collagen-positive cells in the treated IVDs. In all quantitative evaluations, such as MRI and histological and immunohistochemical analyses of IVD degeneration, BMAC-UPAL implantation significantly suppressed the progression of IVD degeneration compared to discectomy and UPAL alone. This preclinical proof-of-concept study demonstrated the potential efficacy of BMAC-UPAL gel as a therapeutic strategy for implementation after discectomy, which was superior to UPAL and discectomy alone in terms of tissue repair and regenerative potential.

Funder

Ministry of Education, Culture, Sports, Science, and Technology of Japan

Publisher

MDPI AG

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