title: Fate of stem cell transplants in peripheral nerves.
abstract: While damaged peripheral nerves demonstrate some potential to regenerate, complete functional recovery remains infrequent, owing to a functional loss of supportive Schwann cells distal to the injury. An emerging solution to improve upon this intrinsic regenerative capacity is to supplement injured nerves with stem cells derived from various tissues. While many of these strategies have proven successful in animal models, few studies have examined the behavior of transplanted stem cells in vivo, including whether they survive and differentiate. In previous work, we demonstrated that cells derived from neonatal rodent dermis (skin-derived precursor cells, or SKPs) could improve regenerative parameters when transplanted distal to both acute and chronic nerve injuries in Lewis rats. The aim of this work was to track the fate of these cells in various nerve injury paradigms and determine the response of these cells to a known glial growth factor. Here, we report that SKPs survive, respond to local cues, differentiate into myelinating Schwann cells, and avoid complete clearance by the host's immune defenses for a minimum of 10weeks. Moreover, the ultimate fate of SKPs in vivo depends on the nerve environment into which they are injected and can be modified by inclusion of heregulin-1β.
authors.affiliation: Hotchkiss Brain Institute and Department of Clinical Neuroscience, Faculty of Medicine, University of Calgary, Canada. skwagg@ucalgary.ca
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Walsh
authors.forename: Ranjan
authors.initials: R
authors.lastname: Kumar
authors.forename: Joey K
authors.initials: JK
authors.lastname: Grochmal
authors.forename: Stephen W P
authors.initials: SW
authors.lastname: Kemp
authors.forename: Joanne
authors.initials: J
authors.lastname: Forden
authors.forename: Rajiv
authors.initials: R
authors.lastname: Midha
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001369:Axons / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D051379:Mice; D009186:Myelin Sheath / Q000187:drug effects / Q000378:metabolism; D020890:Neuregulin-1 / Q000494:pharmacology; D059348:Peripheral Nerve Injuries / Q000473:pathology / Q000628:therapy; D010525:Peripheral Nerves / Q000187:drug effects / Q000473:pathology*; D010641:Phenotype; D051381:Rats; D012867:Skin / Q000166:cytology / Q000187:drug effects; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects
chemical_list: D020890:Neuregulin-1