{
  "abstract": "Introduction This research paper presents a study protocol for an exploratory clinical trial evaluating the safety and potential efficacy of autologous peripheral blood mononuclear cell (PBMNC)-loaded injectable cell scaffold (ICS-001) for angiogenic therapy in chronic limb-threatening ischaemia (CLTI). CLTI, the advanced stage of peripheral artery disease, presents significant therapeutic challenges.Methods and analysis Angiogenic therapy using ICS-001 with PBMNCs—a novel approach designed to enhance local cell retention and promote neovascularisation—will be explored. The study will address the pathophysiology of CLTI, the limitations of current treatments and the rationale for cell-based therapies, alongside the clinical trial design for evaluating the safety and efficacy of ICS-001. We hypothesise that ICS-001 will improve ulcer healing and reduce ischaemic rest pain in patients with CLTI. This paper outlines the methodology, including patient selection, CD34 + cell mobilisation, scaffold preparation, injection protocols, clinical assessments, data collection and safety monitoring. The anticipated results, discussion and conclusion will offer insight into the clinical significance and potential impact of ICS-001 as a pioneering angiogenic therapy for CLTI.Ethics and dissemination The institutional review boards of all participating hospitals approved this study protocol (latest version V.6.0, 5 June 2025). Final data will be made publicly available. A report detailing the study results will be submitted for publication in an appropriate peer-reviewed journal.Data availability statement Data are available on reasonable request. Technical appendix, statistical code is available by contacting the corresponding author. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) licence, which permits others to distribute, remix, adapt, build on this work non-commercially, and licence their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/Trial registration number jRCT2052230115, Japan Registry of Clinical Trials.",
  "authors": [
    {
      "affiliations": [
        "Laboratory of Molecular and Cellular Therapy, Institute for Advanced Medical Sciences, Hyogo Medical University, Nishinomiya, Hyogo Prefecture, Japan"
      ],
      "name": "Kenichi Yamahara"
    },
    {
      "affiliations": [
        "Department of Cardiovascular and Renal Medicine, Hyogo Medical University, Nishinomiya, Hyogo Prefecture, Japan"
      ],
      "name": "Hirokuni Akahori"
    },
    {
      "affiliations": [
        "Department of Plastic Surgery, Hyogo Medical University, Nishinomiya, Hyogo Prefecture, Japan"
      ],
      "name": "Kenichiro Kawai"
    },
    {
      "affiliations": [
        "Department of Cardiovascular and Renal Medicine, Hyogo Medical University, Nishinomiya, Hyogo Prefecture, Japan"
      ],
      "name": "Shinichiro Suna"
    },
    {
      "affiliations": [
        "Department of Respiratory Medicine and Hematology, Hyogo Medical University, Nishinomiya, Hyogo Prefecture, Japan"
      ],
      "name": "Satoshi Yoshihara"
    },
    {
      "affiliations": [
        "Department of Cardiovascular and Renal Medicine, Hyogo Medical University, Nishinomiya, Hyogo Prefecture, Japan"
      ],
      "name": "Masaharu Ishihara"
    },
    {
      "affiliations": [
        "Department of Plastic Surgery, Hyogo Medical University, Nishinomiya, Hyogo Prefecture, Japan"
      ],
      "name": "Masao Kakibuchi"
    },
    {
      "affiliations": [
        "Department of Plastic Surgery, Oita Oka Hospital, Oita, Oita Prefecture, Japan"
      ],
      "name": "Masahide Furukawa"
    },
    {
      "affiliations": [
        "BioX Inc, Tokyo, Japan"
      ],
      "name": "Yasumichi Kogai"
    },
    {
      "affiliations": [
        "Gunze Medical Limited, Osaka, Osaka Prefecture, Japan"
      ],
      "name": "Hideki Sato"
    },
    {
      "affiliations": [
        "Department of Premier Preventive Medicine, Osaka Metropolitan University, Osaka, Osaka Prefecture, Japan"
      ],
      "name": "Shinya Fukumoto"
    },
    {
      "affiliations": [
        "Department of Biological System Engineering, Graduate School of Biology-Oriented Science and Technology, Kindai University, Kinokawa, Wakayama Prefecture, Japan"
      ],
      "name": "Tsutomu Furuzono"
    },
    {
      "affiliations": [
        "Translational Research Center for Medical Innovation, Foundation for Biomedical Research and Innovation at Kobe, Kobe, Hyogo Prefecture, Japan"
      ],
      "name": "Ayumi Tani-Yokoyama"
    },
    {
      "affiliations": [
        "Translational Research Center for Medical Innovation, Foundation for Biomedical Research and Innovation at Kobe, Kobe, Hyogo Prefecture, Japan"
      ],
      "name": "Rika Okamoto"
    },
    {
      "affiliations": [
        "Translational Research Center for Medical Innovation, Foundation for Biomedical Research and Innovation at Kobe, Kobe, Hyogo Prefecture, Japan"
      ],
      "name": "Yasuyuki Fujita"
    },
    {
      "affiliations": [
        "Translational Research Center for Medical Innovation, Foundation for Biomedical Research and Innovation at Kobe, Kobe, Hyogo Prefecture, Japan"
      ],
      "name": "Atsuhiko Kawamoto"
    }
  ],
  "title": "Autologous peripheral blood mononuclear cell-loaded injectable cell scaffold (ICS-001) for revolutionising angiogenic therapy: a study protocol for an exploratory clinical trial",
  "uid": "7bc110dc-3ba9-53ff-9f7b-2d81eec7448a"
}