Stem cell treatment protects against harmful immune response after spinal cord injury in pre-clinical trials

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According to research from Case Western Reserve University (CWRU) School of Medicine, a group of therapeutic cells called multipotent adult progenitor cells (MAPC) can mediate the consequences of the immune system’s harmful second wave response. This can also preserve function which might otherwise be lost. To appear in Scientific Reports, the findings resulted in significant improvements in the motor and urinary functions of animals.

 

MAPCs were shown to have the ability to modulate the behaviour of microphages; allowing them still to clear debris from initial injury, but seemingly avoiding some of the damage to healthy tissue. 

“These were kinder, gentler macrophages,” says Jerry Silver, lead investigator and professor of neurosciences at CWRU. “They do the job, but they pick and choose what they consume. The end result is spared tissue. We don’t know what makes these nicer macrophages more subdued, but this is a subject we are researching in the lab.” 

Biodistribution analysis shows how MAPCs (gold) home to the spleen. The MAPCs were intravenously administered approximately one day after the spinal cord injury. Credit: Scientific Reports.

Research in the Silver lab, conducted by lead author Marc A DePaul, also demonstrated that time is a factor in promoting a positive immune response with MAPCs. MAPCs injected into lab animals one day post-injury travelled primarily into their spleens—a reservoir for immature macrophages—resulting in a beneficial macrophage immune response that spared more spinal cord tissue. Consequently, animals that received treatment demonstrated markedly improved hind-paw motor control and urinary function. It takes approximately a day for the immune system to recognise and then begin to respond to a threat caused by injury or illness. When MAPCs were administered too soon (immediately after injury) or not at all (the control group), the lab animals received no benefit.

“There was this remarkable neuroprotection with the friendlier macrophages,” says Silver. “The spinal cord was just bigger, healthier, with much less tissue damage.”

 

This most recent research complements a discovery from the Silver lab in 2014 where investigators found that a compound they developed, intracellular sigma peptide (ISP), enhances nerve plasticity and regeneration following spinal cord injury. ISP restored considerable function to lab animals in which the compound was tested.

 

“Our dream for the future is to combine the neuroprotection of MAPCs with the neurogenerative capacity of ISP,” says Silver. “Both can be delivered systemically, so there is no need to touch the spinal cord. It is already damaged enough.”

 

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