Advancing Spinal Cord Regeneration - Recent Breakthroughs and Future Directions
Explore recent therapeutic successes and the latest insights into spinal cord biology that are bridging the gap in regenerative medicine. Discover how innovative treatments, from cell therapies to molecular interventions, offer hope for restoring movement in paralyzed individuals.
InBrief
Although made a cliché by TV medical dramas, “you’ll never walk again” remains a harsh reality for victims of spinal-cord injury (SCI). In a split second, victims can go from moving normally to being permanently paralyzed and often requiring aid just to breathe. Our resilient bodies routinely mend broken bones and seal wounds, yet the ability of the body to recover from so devastating an injury has long been beyond our reach. Regenerating damaged tissue of the central nervous system and restoring function in SCI patients is a goal that has captivated medical science for over 100 years. Now, recent therapeutic successes and insights into the underlying biology of the spinal cord have closed the gap between the field of regenerative medicine and restoring movement in paralyzed people.
In 2014, Derek Fidyka, a Polish man rendered paralyzed from the chest down in a 2010 knife attack, miraculously regained the partial use of his legs. His remarkable recovery resulted from a groundbreaking treatment that transplanted specialized cells called olfactory ensheathing cells (OECs) from the patient’s olfactory bulb, a small structure found in the front of the brain. These cells normally guide bundles of nerve fibers to form new synaptic connections between nerve cells.[1] Nerve fibers were taken from Mr. Fidyka’s ankle and implanted into the injured area of the spinal cord; a culture of OECs was injected above and below the area. Eventually, the two cut ends of the spinal cord fused, and Mr. Fidyka regained some movement and feeling in his legs, allowing him to walk, drive, and resume a few functions we normally take for granted.
Although Mr. Fidyka’s recovery is historic, OEC transfer itself does not represent a cure for SCI. Many experts still disagree about the long-term effectiveness of the OEC transplant. The results of most studies show that OEC transfer can improve motor function, but the degree of improvement and long-term outcomes vary greatly and can sometimes worsen SCI-associated pain.[2] Despite early success, the uncertainty of OEC transfer highlights the challenges inherent to treating SCI- the spinal cord is a dauntingly complex structure composed of many different types of cells, and its injuries vary greatly from patient to patient. The mechanisms that allow regeneration differ from one part of the spinal cord to the next. Thus, the location, severity, and time since the injury are all important considerations in finding new ways to repair the damage.[3]
Luckily, these insights are now being applied to a new generation of promising treatments that can be divided roughly into the broad categories of “cell therapies” and “molecular therapies.” Cell therapies use types of stem cells alone or with growth factors to induce the growth of new functional connections between nerve cells.4 Stem cells can be cultured from fetal tissue or taken directly from the patient’s body, as is done in OEC transfer. Molecular therapies, on the other hand, seek to encourage regeneration by directly altering the biologic environment of the injury site, which often has scar tissue, growth inhibitors, and other factors that can prevent regeneration and return to normal function.3 Molecular therapies include compounds that degrade scar tissue and soak up growth inhibitors with sponge-like artificial receptors.4 Specially designed biomaterials with unique physical and electrical properties can act as scaffolds to help guide regrowth of tissue, facilitate the delivery of stem cells, and even directly stimulate the growth of new nerves.[4,5]
The road to advancing treatments for SCI remains long, but anyone paying attention to the field has plenty of reasons to feel hopeful. A growing understanding of the spinal cord’s biology presents opportunities for innovation and enhancement of current therapies. The story of Mr. Fidyka is a rare one, but few successes are infinitely better than none. Mr. Fidyka’s story and the tireless efforts of countless research teams provide much needed hope for both SCI patients and the medical professionals and researchers who strive to help them walk again.
References
Tabakow P, Raisman G, Fortuna W, et al. Functional regeneration of supraspinal connections in a patient with transected spinal cord following transplantation of bulbar olfactory ensheathing cells with peripheral nerve bridging. Cell Transplant. 2014;23: 1631–1655.
Nakhjavan-Shahraki B, Yousefifard M, Rahimi-Movaghar V, et al. Transplantation of olfactory ensheathing cells on functional recovery and neuropathic pain after spinal cord injury; systematic review and meta-analysis. Sci Rep. 2018;8:325.
Sofroniew MV. Dissecting spinal cord regeneration. Nature. 2018;557:343–350.
Dalamagkas K, Tsintou M, Seifalian A, Seifalian AM. Translational regenerative therapies for chronic spinal cord injury. Int J Mol Sci. 2018;19(6). pii: E1776.
Theodore N, Hlubek R, Danielson J, Neff K, Vaickus L, Ulich TR, Ropper AE. First human implantation of a bioresorbable polymer scaffold for acute traumatic spinal cord injury: a clinical pilot study for safety and feasibility. Neurosurgery. 2016;79:E305-E312.
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