About four years ago I suffered an accident that resulted in significant loss of nerve sensation in two fingers. I was carrying a bottle of wine by the neck to a friend’s house, slipped on a wet slimy board, fell down and smashed the bottle on the board. I suffered a slash from the broken glass that nearly caused me to lose two fingers. The surgeon was very skilled. He sewed the tendons and the severed nerves together as best he could. After several surgeries and a long period of recovery the two fingers were saved but the tendon in one finger and the nerve sensation in both fingers were left compromised, a situation that persists to this day. The fingers constantly feel like I am starting to recover from a Novocain shot in them. During my final appointment with the surgeon I asked him “How about injecting a nerve growth factor in my two fingers to restore full sensation in them?” He knew of no such thing and looked at me as if I came from Mars. He said absolutely nothing further could be done.
I look at research related to nerve regeneration in this post, still anticipating the day when the nerves in these fingers can be fully restored. First of all, I need mention that peripheral nerve regrowth can occur naturally after an accident . “Human axon growth rates can reach 2 mm/day in small nerves and 5 mm/day in large nerves(ref).” There is increasing understanding of the factors that impact on nerve growth, such as the role of Schwann cells. “Regeneration of peripheral nerve involves an essential contribution by Schwann cells (SCs) in collaboration with regrowing axons. — Reforming peripheral nerve trucks involves a very close and intimate relationship between axons and Schwann cells that must proliferate and migrate, facilitated by laminin(ref).”
“Schwann cells (also referred to as neurolemnocytes) are a variety of glial cell that keep peripheral nerve fibres (both myelinated and unmyelinated) alive. In myelinated axons, Schwann cells form the myelin sheath(ref)” “During peripheral nerve development the Schwann cell population is expanded so that adequate numbers are available for ensheathment of both nonmyelinated and myelinated nerve fibres. As ensheathment of these fibres progresses each axon–Schwann cell unit becomes surrounded by a basal lamina, providing a unique microtubular framework within the peripheral nerve trunk(ref).”
A plentiful supply of Schwann cells is therefore important to support repair of severed peripheral nerves. So adequate differentiation of stem cells into Schwann cells is required for nerve regeneration, bringing us back to the discussion of the Decline in Adult Stem Cell Differentiation theory of aging. Hair follicle stem cells can be induced to differentiate into Schwann cells and such induction might be an approach to improving nerve regeneration(ref). You might want to read the recent post if you have not already done so.
The process of nerve regrowth can be facilitated or inhibited by various glycoproteins.. For example “Myelin-associated glycoprotein (MAG), a carbohydrate-binding protein on the myelin sheaths that coat nerve cells, inhibits regeneration of damaged neurons by binding to gangliosides on axon surfaces. This interaction causes gangliosides to cluster together, generating a signal that inhibits axon regrowth(ref).” Another nerve growth-inhibiting substance can be “chondroitin sulphate proteoglycans (CSPGs). CSPGs are inhibitory to axon growth in vitro, and regenerating axons stop at CSPG-rich regions in vivo. Removing CSPG glycosaminoglycan (GAG) chains attenuates CSPG inhibitory activity.” — “To test the functional effects of degrading chondroitin sulphate (CS)-GAG after spinal cord injury, we delivered chondroitinase ABC (ChABC) to the lesioned dorsal columns of adult rats. We show that intrathecal treatment with ChABC degraded CS-GAG at the injury site, upregulated a regeneration-associated protein in injured neurons, and promoted regeneration of both ascending sensory projections and descending corticospinal tract axons(ref).”
One important thread of current research involves the use of spinal chord stem cells (ependymal stem cells) to repair spinal chord injuries, a major challenge of nerve regeneration. From a 2007 report of work: “We know that stem cells are present within the spinal cord, but it was not known why they could not function to repair the damage. Surprisingly, we discovered that they actually migrate away from the lesion and the question became why – what signal is telling the stem cells to move.” “The researchers then tested numerous proteins and identified netrin-1 as the key molecule responsible for this migratory pattern of stem cells following injury. In the developing nervous system, netrin-1 acts as a repulsive or attractive signal, guiding nerve cells to their proper targets. In the adult spinal cord, the researchers found that netrin-1 specifically repels stem cells away from the injury site, thereby preventing stem cells from replenishing nerve cells. “When we block netrin-1 function, the adult stem cells remain at the injury site(ref).”
A December 2007 report indicates “A study carried out by researchers at the Kyoto University School of Medicine has shown that when transplanted bone marrow cells (BMCs) containing adult stem cells are protected by a 15mm silicon tube and nourished with bio-engineered materials, they successfully help regenerate damaged nerves(ref).” Another experiment with laboratory animals reported in January of 2009 “found that transplantation of stem cells from the lining of the spinal cord, called ependymal stem cells, reverses paralysis associated with spinal cord injuries(ref).” Finally, I mention that in January 2009, the Geron company got FDA approval for a clinical trial of its embryonic stem cell product GRNOPC1 in patients with acute spinal cord injury(ref).
There are reports also of non stem-cell approaches for dealing with spinal chord injuries, ones that might come under a broad heading of “tissue engineering.” For example, “Northwestern University researchers have shown that a new nano-engineered gel inhibits the formation of scar tissue at the injury site and enables the severed spinal cord fibers to regenerate and grow. The gel is injected as a liquid into the spinal cord and self -assembles into a scaffold that supports the new nerve fibers as they grow up and down the spinal cord, penetrating the site of the injury. When the gel was injected into mice with a spinal cord injury, after six weeks the animals had a greatly enhanced ability to use their hind legs and walk(ref).” Another approach to nerve regeneration reported in March of this year involves engineered transplantable living nerve tissue. ““We have created a three-dimensional neural network, a living conduit in culture, which can be transplanted en masse to an injury site,” explains senior author Douglas H. Smith, MD, Professor, Department of Neurosurgery and Director of the Center for Brain Injury and Repair at Penn. Smith and colleagues have successfully grown, transplanted, and integrated axon bundles that act as ‘jumper cables’ to the host tissue in order to bridge a damaged section of nerve(ref).”
My fantasy is still going back to visit my hand surgeon who will this time give me an injection in each of my semi-numb fingers and assure me that in a couple of months the nerves will have completely grown back. I don’t know when that day will be but I think we are getting closer to it.