Sapporo Medical University's 'autologous serum' stem cells — from stroke research to spinal cord injury approval

Summary — A team at Sapporo Medical University in Japan developed a method of expanding mesenchymal stem cells from the patient's own bone marrow in the patient's own serum and giving them intravenously. In a study of 12 stroke patients (2011) the technique was associated with reported changes in neurological scores and imaging, and it later led to a conditionally approved product for spinal cord injury in Japan in 2018. This article covers the technique, how it developed and the research questions around intravenous delivery.

Why the culture medium matters

To use mesenchymal stem cells as treatment, the small number obtained from bone marrow must be expanded in the laboratory to tens of millions or more. Traditionally, fetal bovine serum has been added to the culture medium to provide the nutrients and growth signals cells need. But animal-derived components carry the possibility of unknown infectious agents and of immune reactions in people, which were noted as challenges for clinical use.

To reduce these problems, the Sapporo team developed a method using serum from the patient's own blood instead of bovine serum. The team reported that cells cultured this way grow quickly, yielding enough cells in a relatively short time — an important advantage in stroke and spinal cord injury, where cells need to be given early after injury.

The 2011 stroke study

The team published in the journal Brain the results of giving a single intravenous infusion of autologous mesenchymal stem cells cultured this way to 12 stroke patients. After infusion, the rate of improvement in neurological deficit scores (NIHSS) increased, and a reduction in lesion volume on MRI was observed in the first week. No serious infusion-related adverse events were reported. However, as a small study without a control group, it could not separate these changes from spontaneous recovery after stroke or the effect of rehabilitation.

Extension to spinal cord injury and the 2018 approval

The team applied the same technology to spinal cord injury, studying intravenous administration relatively early after injury, and a product based on it received conditional, time-limited approval from Japan's Ministry of Health, Labour and Welfare in December 2018 to improve neurological symptoms and functional impairment from spinal cord injury. In 2021 the team reported improvements on the ASIA Impairment Scale and in motor and sensory scores in a case series of 13 patients. As a case of a single culture technology leading through research in two diseases to an approved product, it is often presented as a representative path in Japanese regenerative medicine.

Intravenous studies abroad

In the United States, a phase 1/2 study (2019) giving donor mesenchymal stem cells intravenously to 36 patients more than six months after stroke reported improvements in neurological scores and daily living over 12 months. By contrast, the randomised, double-blind phase 2 MASTERS study (2017), which gave adult progenitor cells (MAPC) to patients with acute stroke, showed no significant difference from placebo in functional recovery at 90 days, with an exploratory finding of a better trend in patients treated earlier. These results show that timing and cell type can affect outcomes.

The question: how do intravenously given cells act on the brain?

The brain is protected by the blood–brain barrier (BBB), which keeps substances in the blood from entering freely. Many intravenously given cells are known to lodge first in other organs such as the lungs, so a key question is whether cells reach the brain directly or act indirectly through secreted factors or whole-body immune modulation. Several hypotheses are being studied — for example, that the barrier weakens soon after brain injury, and that tiny vesicles (exosomes) secreted by cells can cross it. A review of the clinical use of mesenchymal stromal cells also lists clarifying the mechanism as an open task.

In short

Sapporo Medical University's autologous serum culture technique solved the practical problem of preparing cells safely and quickly, and led from stroke research to an approved product for spinal cord injury. Confirming its effect in stroke requires controlled studies, and research on timing and mechanism continues. See the 'Stroke' and 'Spinal Cord Injury' pages for details.

Frequently asked questions

Q. Has Sapporo Medical University's stroke treatment been approved?
The approved product is for spinal cord injury; no mesenchymal stem cell product has been approved for stroke. Confirming an effect in stroke requires controlled studies.

Q. When is the best time to give cells?
Whether the acute, subacute or chronic phase is most suitable has not been determined. MASTERS reported, as an exploratory finding, a better trend in patients treated earlier, while the US phase 1/2 study enrolled chronic-phase patients.

Q. How long does autologous serum culture take?
The culture period varies with the patient's cells, and the team reported that this method is advantageous for obtaining the required number of cells in a relatively short time. Specific periods can be checked in the product's public materials.

How to look up clinical trial information

Ongoing and completed clinical trials can be checked on public registries. ClinicalTrials.gov, run by the U.S. National Library of Medicine, and jRCT, run by Japan's Ministry of Health, Labour and Welfare, publish each study's purpose, eligibility criteria, intervention, outcomes, institutions and status. Results are later published as journal papers, and the reference links below this article lead to the original information. It is also worth knowing that interventions not publicly registered are difficult to verify from outside, in both design and results.

The above summarises results reported in published papers and public-agency materials. University and institute names are given to identify research sources, not to introduce or recommend any medical institution. The suitability of any treatment is decided by the medical team.

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