Research on Allogeneic Cord Blood for Stroke
September 2019 by Frances Verter, PhD
The possibility of using cord blood stem cells to treat adult stroke patients is an area of research that holds enormous potential. Stroke affects one in every six people worldwide, and is the world’s second most common cause of death1-3. The definition of a stroke is the sudden death of brain cells due to lack of oxygen, which happens when blood flow is disrupted in a region of the brain. In about 87% of strokes, the blood flow is disrupted by a blockage, and this is called an ischemic stroke, but stroke can also be caused by bleeding in the brain, and this is called hemorrhagic stroke. Stem cell therapies emerged as a paradigm for stroke about a decade ago. Contrary to long-held beliefs, we now know that the brain can recover to some extent after injury, and stem cell therapy offers a potential for multimodal repair mechanisms. “Immediately after stroke, several events, including edema, deafferentation, and inflammation, occur around the infarct, and some early functional recovery can be attributed to the resolution of edema and inflammation. However, this is usually limited, and other processes, including immunomodulation, angiogenesis, endogenous neurogenesis, and altered gene expression, may be involved in the longer-term recovery of function”. According to the resource CellTrials.org, over the period from January 2018 through July 2019, 77 clinical trials have been registered worldwide to treat stroke with cell therapy, with 68% of the trials listed on ClinicalTrials.gov and 32% listed in 9 other trial registries. The most common source for cells used in stroke cell therapy is bone marrow, at 43% of these 77 trials. Some stroke therapies developed from bone marrow have a strong pipeline of development and are close to approval in their respective countries. The most common cell type used in stroke cell therapy is mesenchymal stem/stromal cells (MSC). The other common group is mononuclear cells (MNC) from a blood-based source comprise 35% of these trials. Stroke therapy with cord blood MNC make up 17% of the total trials. Cord blood is emerging as a serious competitor in cell therapy for stroke. The main reason is because MNC from cord blood trigger less graft-versus–host reaction than adult sources of MNC. Since 2011, every single stroke trial that sourced MNC from bone marrow or peripheral blood relied on autologous cells, where the patient had to undergo a harvest of his or her own cells. A recent trend is for stroke therapy with cord blood cells to push against the envelope of HLA matching. In March 2015, Duke University embarked on a novel phase 1 trial NCT02397018 to test the safety of treating stroke patients with an infusion of cord blood that was completely unmatched except for standard ABO blood typing. Ten patients between ages 45 and 79 that had suffered an ischemic stroke received intravenous infusions within 3 to 10 days after the stroke, and no adverse events related to the therapy were noted. The results from this trial were published in May 20 189. Currently, Duke and collaborators are running a larger phase 2 double-blind trial NCT03004976 at 6 medical centers with the target enrollment of treating 100 patients by March 2020. There are other notable examples of cord blood trials for stroke. The hybrid cord blood bank StemCyte has supported trials NCT01673932 in Hong Kong and NCT02433509 in Taiwan that treated patients with allogeneic cord blood having a minimum 4 out of 6 HLA match. In South Korea, the research center at Bundang CHA Hospital ran trial NCT01884155 in 2013, and in July 2019 they registered a phase 2 trial NCT04013646 that will treat stroke patients with allogeneic cord blood having a minimum 3 out of 6 HLA match. Also in July 2019, the for-profit clinic Blue Horizon International posted ISRCTN10678357 on the WHO trial registry, stating that they had a registry of 97 stroke patients treated in China with cord blood that only had ABO blood type match. If clinical trials of allogeneic cord blood therapy for stroke continue to meet their endpoints, this could be an exciting new application for donated cord blood. In the United States, about 795,000 people suffer a stroke each year, and 140,000 are fatal1-3. If only 1% of these patients received cell therapy, that would be comparable to the total number of allogeneic stem cell transplants per year in the United States. Ultimately, a successful cord blood therapy will find itself in competition against cell therapy products for stroke that are already near approval. The possibility to utilize cord blood cells as an “off-the-shelf” product (actually out of the cryogenic freezer) with no HLA matching would make cord blood more competitive against other cell therapies that are based on MSC and operate as universal donor products. Regardless of how the research on allogeneic cord blood for stroke evolves, it promises to be an exciting topic to follow. https://parentsguidecordblood.org/en/news/research-allogeneic-cord-blood-stroke