Exploratory clinical trial on the safety and capability of dMD-001 in lumbar disc herniation: Study protocol for a first-in-human pilot study

Yamada, Kei; Maeda, Keiko; Ito, Yoichi M.; Inage, Fujio; Isoe, Toshiyuki; Yokota, N; Sugita, Osamu; Sato, Norihiro; Tha, Khin Khin; Iwasaki, Norimasa; Arato, Teruyo; Sudo, Hideki

doi:10.1016/j.conctc.2021.100805

Cited by 9 publications

(35 citation statements)

References 26 publications

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“…1 We previously developed an in situforming sodium alginate gel (dMD-001), which can be filled into the defect in the IVD after discectomy in patients with lumbar IVD herniation and induces tissue repair of the defective disc, 11 12 and conducted a clinical trial. 13 This material gelates within 5 min in situ via calcium ion-mediated crosslinking without resulting in material protrusion after discectomy. 11 12 However, it is thought that there is a limit to the treatment of gel alone in middle-aged and elderly patients with reduced selftissue repair capacity; therefore, the participants in the previous clinical trials were limited to those under 50 years of age.…”

Section: Strengths and Limitations Of This Studymentioning

confidence: 99%

“…11 12 However, it is thought that there is a limit to the treatment of gel alone in middle-aged and elderly patients with reduced selftissue repair capacity; therefore, the participants in the previous clinical trials were limited to those under 50 years of age. 13 A clinical trial of local injection of allogenic bone marrow-derived mesenchymal stem cells (BMSCs) into the IVD found it safe and effective for the treatment of discogenic LBP. 14 However, conventional BMSCs are simply prepared from bone marrow mononuclear cells that adhere to a culture dish and known issues such as quality deterioration during mass culture and difficulty in ensuring quality identity.…”

Section: Strengths and Limitations Of This Studymentioning

confidence: 99%

“…Patients who have previously undergone lumbar surgery or have spine-related systemic diseases will not be considered. 13 In addition, only patients who receive single-level laminoplasty and discectomy will be considered eligible to participate in this trial. Although incidence in younger adults below the age of 50 years is uncommon and this age group will not be included in this study, the age of 20 years is simply set to provide a lower limit of age.…”

Section: Participants and Informed Consentmentioning

confidence: 99%

“…On completion of standard discectomy, the treating surgeon will assess the feasibility of AF reapproximation and make the final decision as to whether the patient will be officially enrolled in the study. 13 Eligible candidates will be treated at Hokkaido University Hospital, Eniwa Hospital or Hokkaido Orthopaedic Memorial Hospital, depending on where the referring orthopaedic surgeons have formal accreditation. The surgical procedure will be performed by the referring surgeons and not a single surgeon.…”

Section: Participants and Informed Consentmentioning

confidence: 99%

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Protocol for treating lumbar spinal canal stenosis with a combination of ultrapurified, allogenic bone marrow-derived mesenchymal stem cells and in situ-forming gel: a multicentre, prospective, double-blind randomised controlled trial

et al. 2023

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IntroductionIn patients with combined lumbar spinal canal stenosis (LSCS), a herniated intervertebral disc (IVD) that compresses the dura mater and nerve roots is surgically treated with discectomy after laminoplasty. However, defects in the IVD after discectomy may lead to inadequate tissue healing and predispose patients to the development of IVD degeneration. Ultrapurified stem cells (rapidly expanding clones (RECs)), combined with an in situ-forming bioresorbable gel (dMD-001), have been developed to fill IVD defects and prevent IVD degeneration after discectomy. We aim to investigate the safety and efficacy of a new treatment method in which a combination of REC and dMD-001 is implanted into the IVD of patients with combined LSCS.Methods and analysisThis is a multicentre, prospective, double-blind randomised controlled trial. Forty-five participants aged 20–75 years diagnosed with combined LSCS will be assessed for eligibility. After performing laminoplasty and discectomy, participants will be randomised 1:1:1 into the combination of REC and dMD-001 (REC-dMD-001) group, the dMD-001 group or the laminoplasty and discectomy alone (control) group. The primary outcomes of the trial will be the safety and effectiveness of the procedure. The effectiveness will be assessed using visual analogue scale scores of back pain and leg pain as well as MRI-based estimations of morphological and compositional quality of the IVD tissue. Secondary outcomes will include self-assessed clinical scores and other MRI-based estimations of compositional quality of the IVD tissue. All evaluations will be performed at baseline and at 1, 4, 12, 24 and 48 weeks after surgery.Ethics and disseminationThis study was approved by the ethics committees of the institutions involved. We plan to conduct dissemination of the outcome data by presenting our data at national and international conferences, as well as through formal publication in a peer-reviewed journal.Trial registration numberjRCT2013210076.

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Section: Strengths and Limitations Of This Studymentioning

confidence: 99%

Section: Strengths and Limitations Of This Studymentioning

confidence: 99%

Section: Participants and Informed Consentmentioning

confidence: 99%

Section: Participants and Informed Consentmentioning

confidence: 99%

See 2 more Smart Citations

Protocol for treating lumbar spinal canal stenosis with a combination of ultrapurified, allogenic bone marrow-derived mesenchymal stem cells and in situ-forming gel: a multicentre, prospective, double-blind randomised controlled trial

et al. 2023

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“…In addition, all the clinical trials have been performed using intradiscal injection therapy for patients with no AF defects, and there have been no clinical applications of soft biomaterials for disc repair therapy after discectomy. That noted, a first human pilot study using an acellular bioresorbable UPAL gel in patients with lumbar disc herniation has been conducted [ 246 ]. In a preclinical study using a large-animal discectomy model, the UPAL gel not only exhibited sufficient biomechanical properties without protrusion but also histologically promoted disc repair [ 7 ].…”

Section: Disc Regeneration And/or Repair Treatment For Ivd Herniationmentioning

confidence: 99%

Biomaterials and Cell-Based Regenerative Therapies for Intervertebral Disc Degeneration with a Focus on Biological and Biomechanical Functional Repair: Targeting Treatments for Disc Herniation

Yamada

Iwasaki

Sudo

2022

Cells

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Intervertebral disc (IVD) degeneration is a common cause of low back pain and most spinal disorders. As IVD degeneration is a major obstacle to the healthy life of so many individuals, it is a major issue that needs to be overcome. Currently, there is no clinical treatment for the regeneration of degenerated IVDs. However, recent advances in regenerative medicine and tissue engineering suggest the potential of cell-based and/or biomaterial-based IVD regeneration therapies. These treatments may be indicated for patients with IVDs in the intermediate degenerative stage, a point where the number of viable cells decreases, and the structural integrity of the disc begins to collapse. However, there are many biological, biomechanical, and clinical challenges that must be overcome before the clinical application of these IVD regeneration therapies can be realized. This review summarizes the basic research and clinical trials literature on cell-based and biomaterial-based IVD regenerative therapies and outlines the important role of these strategies in regenerative treatment for IVD degenerative diseases, especially disc herniation.

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Biomimetic Microstructural Materials for Intervertebral Disk Degeneration Repair

Li,

Yuan,

Cai

et al. 2024

Small Structures

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The intervertebral disks (IVD) serve as shock absorbers in the spine. As the largest avascular tissue in the human body, it has a limited capacity for regeneration. To address this issue, various innovative biomimetic materials have been explored to facilitate IVD regeneration at both microscopic and macroscopic levels. Techniques such as electrostatic spinning and fiber‐winding machines have been employed to prepare biomimetic materials. In this review, the physiological structure of the IVD is described, and advanced studies on its microstructure are summarized. The techniques used in biomimetic biomaterial development are further investigated, and biomimetic materials that facilitate IVD regeneration are systematically explored. Specifically, this article provides a detailed description and summary of the key features of biomimetic materials, including the types of loads they can withstand and their regenerative effects. Finally, a prospective outlook for the development and application of biomimetic materials in IVD regeneration is presented.

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Exploratory clinical trial on the safety and capability of dMD-001 in lumbar disc herniation: Study protocol for a first-in-human pilot study

Cited by 9 publications

References 26 publications

Protocol for treating lumbar spinal canal stenosis with a combination of ultrapurified, allogenic bone marrow-derived mesenchymal stem cells and in situ-forming gel: a multicentre, prospective, double-blind randomised controlled trial

Protocol for treating lumbar spinal canal stenosis with a combination of ultrapurified, allogenic bone marrow-derived mesenchymal stem cells and in situ-forming gel: a multicentre, prospective, double-blind randomised controlled trial

Biomaterials and Cell-Based Regenerative Therapies for Intervertebral Disc Degeneration with a Focus on Biological and Biomechanical Functional Repair: Targeting Treatments for Disc Herniation

Biomimetic Microstructural Materials for Intervertebral Disk Degeneration Repair

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