Osamu Honmou1, Toshihiko Yamashita2, Tomonori Morita3, Tsutomu Oshigiri3, Ryosuke Hirota3, Satoshi Iyama4, Junji Kato5, Yuichi Sasaki6, Sumio Ishiai7, Yoichi M Ito8, Ai Namioka9, Takahiro Namioka9, Masahito Nakazaki9, Yuko Kataoka-Sasaki10, Rie Onodera9, Shinichi Oka10, Masanori Sasaki11, Stephen G Waxman12, Jeffery D Kocsis12. 1. Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Hokkaido, Japan; Department of Advanced Regenerative Therapeutics, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Hokkaido, Japan; Department of Neurology, Yale University School of Medicine, New Haven, CT, 06510, USA. 2. Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Hokkaido, Japan. 3. Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Hokkaido, Japan; Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Hokkaido, Japan. 4. Department of Hematology, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Hokkaido, Japan. 5. Department of Medical Oncology, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Hokkaido, Japan. 6. Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Hokkaido, Japan; Department of Rehabilitation, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Hokkaido, Japan. 7. Department of Rehabilitation, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Hokkaido, Japan. 8. Biostatistics Division, Hokkaido University Hospital Clinical Research and Medical Innovation Center, Sapporo, Hokkaido, 060-8648, Japan. 9. Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Hokkaido, Japan. 10. Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Hokkaido, Japan; Department of Advanced Regenerative Therapeutics, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Hokkaido, Japan. 11. Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Hokkaido, Japan; Department of Advanced Regenerative Therapeutics, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Hokkaido, Japan; Department of Neurology, Yale University School of Medicine, New Haven, CT, 06510, USA. Electronic address: msasaki@sapmed.ac.jp. 12. Department of Neurology, Yale University School of Medicine, New Haven, CT, 06510, USA.
Abstract
BACKGROUND: Although spinal cord injury (SCI) is a major cause of disability, current therapeutic options remain limited. Recent progress in cellular therapy with mesenchymal stem cells (MSCs) has provided improved function in animal models of SCI. We investigated the safety and feasibility of intravenous infusion of MSCs for SCI patients and assessed functional status after MSC infusion. METHODS: In this phase 2 study of intravenous infusion of autologous MSCs cultured in auto-serum, a single infusion of MSCs under Good Manufacturing Practice (GMP) production was delivered in 13 SCI patients. In addition to assessing feasibility and safety, neurological function was assessed using the American Spinal Injury Association Impairment Scale (ASIA), International Standards for Neurological and Functional Classification of Spinal Cord (ISCSCI-92). Ability of daily living was assessed using Spinal Cord Independence Measure (SCIM-III). The study protocol was based on advice provided by the Pharmaceuticals and Medical Devices Agency in Japan. The trial was registered with the Japan Medical Association (JMA-IIA00154). RESULTS: No serious adverse events were associated with MSC injection. There was neurologic improvement based on ASIA grade in 12 of the 13 patients at six months post-MSC infusion. Five of six patients classified as ASIA A prior to MSC infusion improved to ASIA B (3/6) or ASIA C (2/6), two ASIA B patients improved to ASIA C (1/2) or ASIA D (1/2), five ASIA C patients improved and reached a functional status of ASIA D (5/5). Notably, improvement from ASIA C to ASIA D was observed one day following MSC infusion for all five patients. Assessment of both ISCSCI-92, SCIM-III also demonstrated functional improvements at six months after MSC infusion, compared to the scores prior to MSC infusion in all patients. CONCLUSION: While we emphasize that this study was unblinded, and does not exclude placebo effects or a contribution of endogenous recovery or observer bias, our observations provide evidence supporting the feasibility, safety and functional improvements of infused MSCs into patients with SCI.
BACKGROUND: Although spinal cord injury (SCI) is a major cause of disability, current therapeutic options remain limited. Recent progress in cellular therapy with mesenchymal stem cells (MSCs) has provided improved function in animal models of SCI. We investigated the safety and feasibility of intravenous infusion of MSCs for SCI patients and assessed functional status after MSC infusion. METHODS: In this phase 2 study of intravenous infusion of autologous MSCs cultured in auto-serum, a single infusion of MSCs under Good Manufacturing Practice (GMP) production was delivered in 13 SCI patients. In addition to assessing feasibility and safety, neurological function was assessed using the American Spinal Injury Association Impairment Scale (ASIA), International Standards for Neurological and Functional Classification of Spinal Cord (ISCSCI-92). Ability of daily living was assessed using Spinal Cord Independence Measure (SCIM-III). The study protocol was based on advice provided by the Pharmaceuticals and Medical Devices Agency in Japan. The trial was registered with the Japan Medical Association (JMA-IIA00154). RESULTS: No serious adverse events were associated with MSC injection. There was neurologic improvement based on ASIA grade in 12 of the 13 patients at six months post-MSC infusion. Five of six patients classified as ASIA A prior to MSC infusion improved to ASIA B (3/6) or ASIA C (2/6), two ASIA B patients improved to ASIA C (1/2) or ASIA D (1/2), five ASIA C patients improved and reached a functional status of ASIA D (5/5). Notably, improvement from ASIA C to ASIA D was observed one day following MSC infusion for all five patients. Assessment of both ISCSCI-92, SCIM-III also demonstrated functional improvements at six months after MSC infusion, compared to the scores prior to MSC infusion in all patients. CONCLUSION: While we emphasize that this study was unblinded, and does not exclude placebo effects or a contribution of endogenous recovery or observer bias, our observations provide evidence supporting the feasibility, safety and functional improvements of infused MSCs into patients with SCI.
Authors: Emmanouil I Damianakis; Ioannis S Benetos; Dimitrios Stergios Evangelopoulos; Aikaterini Kotroni; John Vlamis; Spyridon G Pneumaticos Journal: Cureus Date: 2022-04-28
Authors: Ria Margiana; Alexander Markov; Angelina O Zekiy; Mohammed Ubaid Hamza; Khalid A Al-Dabbagh; Sura Hasan Al-Zubaidi; Noora M Hameed; Irshad Ahmad; R Sivaraman; Hamzah H Kzar; Moaed E Al-Gazally; Yasser Fakri Mustafa; Homayoon Siahmansouri Journal: Stem Cell Res Ther Date: 2022-07-28 Impact factor: 8.079