Improving Cell Transplantation After Spinal Cord Injury

A 1744 illustration by Bartolomeo Eustachi showing the central nervous system (brain and spinal cord) and some peripheral nerves branching off. Image credit: Welcome Library, London // CC BY 4.0

Most spinal cord injuries (SCIs) are the result of traumatic accidents on the road or in sports. Every year, there are 17,000 new cases of SCI in the U.S., adding to approximately 282,000 current cases [PDF]. These injuries can have devastating consequences for patients such as paralysis and loss of key functions and independence.

One research approach that has shown success in restoring function after such injuries in animal models is the transplantation of olfactory ensheathing cells (OECs) into the damaged areas. OECs, a form of glial cells, are a unique tissue found only in the back of the nasal cavity with the ability to support neurogenesis—the regrowth of neurons—and to help reform synapses with minimal chance of graft rejection or need of immunosuppressant drugs.

However, the literature gathered over more than two decades does not reveal specifics and the numbers may be overinflated due to inaccurate data, according to a new literature review published in PLOS Biology.

To get a better baseline of understanding about how, when, and where to transplant OECs, researchers Ralf Watzlawick, Jan Schwab, and colleagues at the Ohio State University Wexner Medical Center, Charite Universtaetsmedizin Berlin, and the CAMARADES consortium (Collaborative Approach to Meta Analysis and Review of Animal Data from Experimental Studies) conducted a literature review spanning more than six decades—from 1949 to 2014—which featured data on 62 experiments and 1164 animals.

The researchers began by using statistical models commonly used to detect publication bias known as Egger’s regression and funnel plotting. Publication bias is the tendency to publish some research findings over others, especially those that report significant results. Those models “helped us to be more accurate,” Schwab, a clinical neuroscientist and professor of neuroscience at the Ohio State University, who is currently working in Berlin, Germany, tells mental_floss. “If you just look at what [studies are] published, we get an impression that is way too positive, because there is missing data that is not published. We used statistics to unmask this missing data and get a complete picture of the real distribution of the data.”

This “real distribution” revealed that injured rodent models showed an overall improvement rate of 20.3 percent in the animals after transplantation of OECs and 19.2 percent improvement in locomotion. While not as high as some of the past research has shown (some studies reported as high as 50.3 percent improvement rates), Schwab says this statistically relevant number justifies the transplantation of OECs in treating spinal cord injury.

“This is not a theoretical exercise or just a literature review; it’s applying statistical tools to get closer to the true effect of an intervention for cell transplantation,” Schwab says. “I think this will be influential in shaping experimental models, how to transplant cells in the best manner, optimizing effect size.”  He feels this review may apply to cell transplantation in general, not just OECs.

While a lot of effort was spent in past research on optimizing the cells themselves for transplantation, most research ignored “where to transplant cells, and also in which concentrations you would inject those cells,” he says.

Schwab and his colleagues are currently preparing two “sister papers” to check for other promising strategies to prioritize different approaches to prepare for clinical trials. He says he's excited that now they can come up with a new baseline of data that “characterizes the best way to transplant cells into an injured spinal cord.”