Intravenous Infusion of Autoserum-Expanded Autologous Mesenchymal Stem Cells in Patients With Chronic Brain Injury: Protocol for a Phase 2 Trial

Shinichi Oka; Tomohiro Yamaki; Masanori Sasaki; Ryo Ukai; Mitsuhiro Takemura; Takahiro Yokoyama; Yuko Kataoka-Sasaki; Rie Onodera; Yoichi M Ito; Shigeki Kobayashi; Jeffery D Kocsis; Yasuo Iwadate; Osamu Honmou

doi:10.2196/37898

Intravenous Infusion of Autoserum-Expanded Autologous Mesenchymal Stem Cells in Patients With Chronic Brain Injury: Protocol for a Phase 2 Trial

JMIR Res Protoc. 2022 Jul 6;11(7):e37898. doi: 10.2196/37898.

Authors

Shinichi Oka^{1

2}, Tomohiro Yamaki³, Masanori Sasaki^{1

2

4}, Ryo Ukai¹, Mitsuhiro Takemura¹, Takahiro Yokoyama¹, Yuko Kataoka-Sasaki^{1

2}, Rie Onodera¹, Yoichi M Ito⁵, Shigeki Kobayashi³, Jeffery D Kocsis^{4

6}, Yasuo Iwadate⁷, Osamu Honmou^{1

2

4}

Affiliations

¹ Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
² Department of Advanced Regenerative Therapeutics, Sapporo Medical University School of Medicine, Sapporo, Japan.
³ Division of Neurosurgery, Rehabilitation Center for Traumatic Apallics Chiba, National Agency for Automotive Safety and Victims' Aid, Chiba, Japan.
⁴ Department of Neurology, Yale University School of Medicine, New Haven, CT, United States.
⁵ Data Science Center, Institute of Health Science Innovation for Medical Care, Hokkaido University Hospital, Sapporo, Japan.
⁶ Department of Neuroscience, Yale University School of Medicine, New Haven, CT, United States.
⁷ Department of Neurological Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.

PMID: 35793128
PMCID: PMC9301565
DOI: 10.2196/37898

Abstract

Background: Brain injuries resulting from motor vehicle accidents and falls, as well as hypoxic insults and other conditions, are one of the leading causes of disability and death in the world. Current treatments are limited but include continuous rehabilitation, especially for chronic brain injury. Recent studies have demonstrated that the intravenous infusion of mesenchymal stem cells (MSCs) has therapeutic efficacy for several neurological diseases, including stroke and spinal cord injury.

Objective: The objective of our investigator-initiated clinical trial is to assess the safety and potential efficacy of the intravenous infusion of autoserum-expanded autologous MSCs for patients with chronic brain injury.

Methods: The (phase 2) trial will be a single-arm, open-label trial with the primary objective of confirming the safety and efficacy of autoserum-expanded autologous MSCs (STR-01; produced under good manufacturing practices) when administered to patients with chronic brain injury. The estimated number of enrolled participants is 6 to 20 patients with a modified Rankin Scale grade of 3 to 5. The assessment of safety and the proportion of cases in which the modified Rankin Scale grade improves by 1 point or more at 180 days after the injection of STR-01 will be performed after MSC infusion.

Results: We received approval for our clinical trial from the Japanese Pharmaceuticals and Medical Devices Agency on December 12, 2017. The trial will be completed on June 11, 2023. The registration term is 5 years. The recruitment of the patients for this trial started on April 20, 2018, at Sapporo Medical University Hospital in Japan.

Conclusions: Our phase 2 study will aim to address the safety and efficacy of the intravenous infusion of MSCs for patients with chronic brain injury. The use of STR-01 has been performed for patients with cerebral infarction and spinal cord injury, providing encouraging results. The potential therapeutic efficacy of the systemic administration of autoserum-expanded autologous MSCs for chronic brain injury should be evaluated, given its safety and promising results for stroke and spinal cord injury.

Trial registration: Japan Medical Association Center for Clinical Trials JMA-IIA00333; https://tinyurl.com/nzkdfnbc.

International registered report identifier (irrid): DERR1-10.2196/37898.

Keywords: autologous mesenchymal stem cells; brain; brain injury; cell therapy; chronic brain injury; falls; hypoxia; intravenous delivery; motor vehicle accident; rehabilitation; stem cells.

©Shinichi Oka, Tomohiro Yamaki, Masanori Sasaki, Ryo Ukai, Mitsuhiro Takemura, Takahiro Yokoyama, Yuko Kataoka-Sasaki, Rie Onodera, Yoichi M Ito, Shigeki Kobayashi, Jeffery D Kocsis, Yasuo Iwadate, Osamu Honmou. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 06.07.2022.