, results from a single-arm, phase I trial demonstrated. Unlike autologous mesenchymal stem cells, mononuclear cells (MNCs) do not require passage in culture, which allows for testing in the early poststroke time therapy window.
Bone marrow MNCs are attractive in regenerative medicine studies because they can be rapidly isolated; are enriched with hematopoietic, mesenchymal, and endothelial progenitor cells; and permit autologous applications. “The regenerative potential of bone marrow–derived MNCs is attributed to various mechanisms that impact stroke recovery,” researchers led by, wrote in a study published online Sept. 17 in . “These cells migrate to the site of injury, release cytokines and other trophic factors, decrease proinflammatory and upregulate anti-inflammatory pathways, and enhance angiogenesis, neurogenesis, and synaptogenesis.”
For the trial, Dr. Savitz, MD, director of the Institute for Stroke and Cerebrovascular Disease at UTHealth, Houston, and colleagues recruited 25 patients to receive an IV dose of their own bone marrow mononuclear cells within 72 hours after stroke onset, a time frame supported by previous preclinical studies. They followed the patients for 1 year and compared the results with a control group of 185 patients who received conventional poststroke treatment. Primary outcomes were study-related serious adverse events and the proportion of patients successfully completing study intervention.
The researchers reported results from 25 patients who received bone marrow MNCs. The mean age of patients in the MNC and control groups were 61 and 63 years, respectively, 53% were female, and 69% were white. No study-related adverse events were observed in the MNC group, but three (12%) had infarct expansion between enrollment and harvest and underwent elective hemicraniectomy after cell infusion.
Advanced magnetic resonance imaging revealed that the average mean fractional anisotropy (FA), a measure of structural integrity and directional coherence of axonal fibers, within the ipsilesional pons was decreased between 1 and 3 months after stroke, “which translated to a relative FA [rFA] comparable with prior reports at this time point,” the researchers wrote. “However, by 6 months, mean rFA began to increase and by 2 years it was significantly higher than at 1 month. This increasing trend in rFA may imply an increase in axonal and fiber coherence as well as thickness in myelin sheets, suggesting microstructural repair. However, without a comparable group of stroke patients not treated with MNCs, we cannot directly ascribe the white matter changes to MNC treatment.”
In light of the findings, the researchers concluded that MNCs “pose no additional harm in ischemic stroke patients when given during the acute phase, doses up to 10 million cells per kilogram are tolerated, and it is feasible to perform a bone marrow harvest and reinfusion of MNCs for a wide range of stroke patients. Well-designed RCTs are needed to further assess safety and efficacy of this novel investigational approach to enhance stroke recovery.”
The study was supported by grants from the National Institutes of Health. Dr. Savitz and many of his coauthors disclosed having numerous financial ties to the pharmaceutical and biotechnology industries.