CHICAGO — Neurotrophic factors can be introduced using stem cells and, along with the plant alkaloid vincristine, can be used to selectively reinnervate the larynx in rat models, a researcher from Indiana University said here on April 29 at the Annual Meeting of the Triological Society, held as part of the Combined Otolaryngology Spring Meetings.
The study, which received the society’s Fowler Award, introduces a technique that could help patients with recurrent laryngeal nerve injury, according to the author.
Previous studies have shown that recurrent laryngeal nerve injury is followed by a high rate of spontaneous but abnormal reinnervation (Ann Otol Rhinol Laryngol. 2007;116(1):57-65); that vincristine, an alkaloid traditionally used to treat leukemia and some other cancers, can be used to prevent these aberrations (Laryngoscope. 2001;111(5):786-791); and that neurotrophic factor, such as IGF-1, can lead to enhanced reinnervation (Arch Otolaryngol Head Neck Surg. 1999;125:274-279). But this plasmid use is hindered by inefficient and unreliable gene transfers, said Stacey Halum, MD, assistant professor of otolaryngology-head and neck surgery at the Indiana University School of Medicine in Indianapolis. “Our concept was, if we could use stem cells as vectors to deliver neurotrophic factor, we could potentially selectively enhance reinnervation to certain muscles,” Dr. Halum said, “whereas we could use vincristine, in Paniello’s approach, to prevent antagonistic reinnervation. And this may allow us to selectively restore adductor activity.”
Stem Cell Selection
The research group chose to use muscle stem cells, Dr. Halum said, because they could obtain therapeutic quantities with just a small muscle biopsy and for their ease of transduction. Researchers used ciliary neurotrophic factor (CNTF) after finding that 90 percent of cells survived in a muscle stem cell survival assay, compared to 50 percent in a saline group. The researchers then developed a lentivirus to encode the CNTF, finding they could do so with 92 percent efficiency, Dr. Halum said. In a pilot study, they established that vincristine could be used next to stem cells with no adverse effects on the stem cells’ reinnervation effects.
Finally, rat models were divided into five groups, with six in each group: a saline control group; a group with enhanced green fluorescent protein (EGFP)-expressing stem cells injected into the thyroarytenoid (TA) muscle and saline into the posterior cricoarytenoid (PCA) muscle; CNTF-expressing stem cells into the TA and saline into the PCA; EGFP-expressing stem cells into the TA and vincristine into the PCA; and CNTF-expressing stem cells into the TA and vincristine into the PCA.