Bone marrow-derived stem cells delivered directly into the bloodstream can improve movement and recovery in rats with spinal cord injuries. The rat model findings prompted human trials that last year earned a ‘Sakigake’ breakthrough designation from Japanese regulators.
“We are now applying for approval from the Japanese government for this approach to be used clinically,” says lead investigator Osamu Honmou, a professor and chair of the Department of Neural Regenerative Medicine at Sapporo Medical University School of Medicine.
The research project dates back 25 years to rodent experiments by Honmou and colleagues involving mesenchymal stem cells (MSCs) from bone marrow. That work culminated in a 2010 report showing that rat MSCs, when infused into the leg vein of another rat that had a spinal cord injury, could improve the latter’s hind-limb motor function1.
This was the first evidence of benefit via intravenous delivery. Previous studies from Honmou’s team and others had reported a similar benefit, but only by injecting MSCs directly into the spinal cord — a more dangerous and complicated channel.
Jeffery Kocsis, a close collaborator of Honmou’s from the Yale School of Medicine in the United States, subsequently showed that the infused MSCs help reduce leakage from blood vessels into the damaged spinal cord, among other protective mechanisms2.
In 2016, Honmou and Sapporo Medical University’s Masanori Sasaki reported that the MSC therapy worked even months after the initial injury in the rats3. “This study helped to facilitate the clinical translation of this approach to the chronic stage of spinal cord injury,” says Sasaki, noting that there are no therapies currently approved for people with established spinal cord injuries.
There are also few effective therapies for people with recent trauma to the spine. In 2013 Honmou and orthopaedic surgeon Toshihiko Yamashita launched a trial at Sapporo Medical University to test the efficacy and safety of infusing a patient’s own MSCs for people with spinal injuries who are still in this acute or sub-acute period.
“We have a unique cell processing centre that allows us to rigorously and efficiently prepare cells for the studies,” notes Honmou. “This is important because in some studies the cell preparation between patients is not well-defined, which could lead to inconsistent results.”
The preclinical and clinical studies are “progressing very well,” says Kocsis, who has visited Sapporo often during the course of the studies. The approach’s therapeutic potential, he adds, is “quite exciting.”
- Osaka, M. et al. Intravenous administration of mesenchymal stem cells derived from bone marrow after contusive spinal cord injury improves functional outcome. Brain Research 1343, 226–235 (2010). | article
- Matsushita, T. et al. Diffuse and persistent blood-spinal cord barrier disruption after contusive spinal cord injury rapidly recovers following intravenous infusion of bone marrow mesenchymal stem cells. Experimental Neurology 267, 152–164 (2015). | article
- Morita, T. et al. Intravenous infusion of mesenchymal stem cells promotes functional recovery in a model of chronic spinal cord injury. Neuroscience 335, 221–231 (2016). | article
About the Researcher
Osamu Honmou, Chairman and Professor at the Department of Neural Regenerative Medicine, Sapporo Medical University. Lecturer in the Department of Neurology, Yale School of Medicine, Yale University
Professor Osamu Honmou is a board-certified neurosurgeon, who has led preclinical and clinical investigations testing the use of bone marrow-derived stem cells for the treatment of stroke and spinal cord injury.