This study examined Schwann cell behavior during paranodal demyelination induced by beta,beta'-iminodipropionitrile (IDPN). The stimuli for Schwann cell proliferation, extensively studied in vitro, are less well understood in vivo. Most in vivo systems previously used to examine Schwann cell proliferation in disease are dominated by loss of internodal myelin sheaths. As used in this study, IDPN administration produces neurofilamentous axonal swellings and paranodal demyelination, without segmental demyelination or fiber degeneration. We asked whether Schwann cells would proliferate following the restricted paranodal demyelination that accompanies the axonal swellings, and if so what the sources and distributions of new Schwann cells might be. IDPN was given as a single large dose (2 ml/kg) to 21-d-old rats. Neurofilamentous axonal swellings formed in the proximal regions of motor axons, reaching their greatest enlargement in the root exit zone 8 d after IDPN administration. These swellings subsequently migrated distally down the nerves at rates approaching 1 mm/d. The axonal enlargement was consistently associated with displacement of the myelin sheath attachment sites into internodal regions, and consequent paranodal demyelination. This stage was associated with perikaryal changes, including nucleolar enlargement, "girdling" of the perikaryon, and formation of attenuated stalks separating the perinuclear region from the external cytoplasmic collar. Schwann cells proliferated abundantly during this stage. Daughter Schwann cells migrated within the endoneurial space (outside the nerve fiber basal laminae) to overlie the demyelinated paranodes of swollen nerve fibers. In these regions, local proliferation of Schwann cells continued, resulting in large paranodal clusters of Schwann cells. As the axonal calibers subsequently returned to normal, the outermost myelin lamellae of the original internodes returned to their paranodal attachment sites and the supernumerary Schwann cells disappeared. Formation of short internodes, segmental demyelination, and nerve fiber loss were rare phenomena. These results indicate that paranodal demyelination is a sufficient stimulus to excite abundant Schwann cell proliferation; neither internodal demyelination nor myelin breakdown is a necessary stimulus for mitosis. The 3H-thymidine incorporation studies indicated that the sources of new Schwann cells included markedly increased division of the Schwann cells of unmyelinated fibers and, as they formed, supernumerary Schwann cells. In addition, there were rare examples of 3H-thymidine incorporation by Schwann cells associated with myelinated nerve fibers.(ABSTRACT TRUNCATED AT 400 WORDS)
BACKGROUND Patients with blood, immune, or metabolic diseases may require a stem cell transplant as part of their treatment. However, 70% of patients do not have a suitable human leukocyte antigen match in their family, and need an unrelated donor. Individuals can register as potential donors at stem cell drives, where they provide consent and a tissue sample for human leukocyte antigen typing. The ideal donors are young, male, and from a diversity of ethnic backgrounds. However, in Canada, non‐Caucasian males ages 17 to 35 years represent only 8.8% of listed donors. STUDY DESIGN AND METHODS The Stem Cell Club is a non‐profit organization founded in 2011 in Canada that aims to augment recruitment of the most needed donors. The initiative published a recruitment toolkit online (http://www.stemcellclub.ca). Currently, there are 12 chapters at universities across Canada. RESULTS To date, the Stem Cell Club has recruited 6585 potential registrants, representing 1.63% of donors on Canada's donor‐database. Of the recruited registrants, 58.3% were male; 60.3% of males self‐reported as non‐Caucasian, and 78.5% were ages 17 to 25 years. From 2015 to 2016, the initiative recruited 13.7% of all ethnically diverse males ages 17 to 35 years listed in Canada's donor database. Data from this initiative demonstrate sustainability and performance on key indicators of stem cell drive quality. CONCLUSION The Stem Cell Club has developed a capacity to recruit 2600 donors annually, with the majority being males with a high degree of ethnic diversity. The initiative enhances the quality of Canada's unrelated donor‐database, improving the chances that patients in need of an unrelated donor will find a match for transplant. The Stem Cell Club is a model relevant to recruitment organizations around the world.
Dr. Dylan Bould is an anesthesiologist at CHEO (Children’s Hospital of Eastern Ontario) and Director of Education Research at the University of Ottawa’s Department of Anesthesiology. Dr. Bould began training in anesthesia in the U.K. and completed fellowships in pediatric anesthesia and medical education at SickKids and St. Michael’s Hospital in Toronto, as well as a pediatric cardiac anesthesia fellowship in London, England. Over the course of his fellowships in Toronto, Dr. Bould completed a Master of Education at the University of Toronto focusing on medical education. Dr. Bould is also involved in global health, having worked in Nepal and Kenya, and was part of the organization process of the University of Zambia Anesthesia Residency Program. Dr. Bould’s current research focuses on hierarchy in medical training, mentorship in medical education, and simulation in healthcare education. RésuméDr Dylan Bould est un anesthésiologiste au Centre hospitalier pour enfants de l’est de l’Ontario (CHEO) et le directeur de la recherche en enseignement au département d’anesthésie de l’Université d’Ottawa. Dr Bould a commencé sa formation en anesthésie au Royaume-Uni et a complété des formations complémentaires (fellowships) en anesthésie pédiatrique et en enseignement médical à SickKids et à l’Hôpital St Michael à Toronto, ainsi qu’une formation en anesthésie cardiaque pédiatrique à Londres, en Angleterre. Au cours de ses formations complémentaires à Toronto, Dr Bould a complété une maîtrise en éducation à l’Université de Toronto axée sur l’enseignement médical. Dr Bould est également impliqué dans le domaine de la santé mondiale, ayant travaillé au Népal et au Kenya, et ayant aidé à mettre sur pied le programme de résidence en anesthésie à l’Université de la Zambie. La recherche actuelle de Dr Bould se concentre sur la hiérarchie présente lors de la formation médicale, le mentorat en enseignement médical, et la simulation dans l’enseignement des soins de santé.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.