Pre-Existing Inflammatory Diseases Reduce Therapeutic Potential of Stem Cells for MS Treatment, Study Shows

Pre-existing inflammatory diseases affecting the central nervous system make mesenchymal stem cells (MSCs) less effective in treating multiple sclerosis (MS), concludes a study by researchers at Cleveland’s Case Western Reserve University School of Medicine.

The study, “CNS disease diminishes the therapeutic functionality of bone marrow mesenchymal stem cells,” notes that MSCs potentially produce several signaling proteins that can regulate immune system responses as well as help tissue regenerate. Preclinical studies have shown that this can reduce brain inflammation while improving neural repair in animal models of experimental autoimmune encephalomyelitis (EAE). This model resembles the inflammation and neuronal damage seen in MS patients.

Given the need for effective new MS therapies, the results will help MSCs to advance to human clinical trials. So far, results have reported good safety data, though such therapies have failed to demonstrate therapeutic efficacy. Most such trials so far have used stem cells collected from the patient, a process known as autologous transplantation — yet this may explain why MSCs have not been effective. It’s possible that pre-existing neurological conditions may alter stem cells’ responsiveness as well as their therapeutic activity.

To see whether that is in fact the case, team members collected stem cells from the bone marrow of EAE mice. But these stem cells were unable to improve EAE symptoms, whereas stem cells collected from healthy mice retained all their therapeutic potential and improved EAE symptoms.

A more detailed analysis showed that the MSCs derived from EAE animals had different features than their healthy counterparts.

In addition, the team confirmed that MSCs collected from MS patients were also less effective in treating EAE animals, compared to MSCs from healthy controls. Indeed, these MSCs from patients produced pro-inflammatory signals instead of the protective anti-inflammatory ones.

“Diseases like EAE and MS diminish the therapeutic functionality of bone marrow MSCs, prompting re- evaluation about the ongoing use of autologous MSCs as a treatment for MS,” the team wrote, adding that its study supports the advancement of MSC therapy from donors rather than autologous MSC therapy to treat MS while raising “important concerns over the efficacy of using autologous bone marrow MSCs in clinical trials.”