Intrinsic differences among spatially distinct neural crest stem cells in terms of migratory properties, fate determination, and ability to colonize the enteric nervous system.
We have systematically examined the developmental potential of neural crest stem cells from the enteric nervous system (gut NCSCs) in vivo to evaluate their potential use in cellular therapy for Hirschsprung disease and to assess differences in the properties of postmigratory NCSCs from different regions of the developing peripheral nervous system (PNS). When transplanted into developing chicks, flow-cytometrically purified gut NCSCs and sciatic nerve NCSCs exhibited intrinsic differences in migratory potential and neurogenic capacity throughout the developing PNS. Most strikingly, gut NCSCs migrated into the developing gut and formed enteric neurons, while sciatic nerve NCSCs failed to migrate into the gut or to make enteric neurons, even when transplanted into the gut wall. Enteric potential is therefore not a general property of NCSCs. Gut NCSCs also formed cholinergic neurons in parasympathetic ganglia, but rarely formed noradrenergic sympathetic neurons or sensory neurons. Supporting the potential for autologous transplants in Hirschsprung disease, we observed that Endothelin receptor B (Ednrb)-deficient gut NCSCs engrafted and formed neurons as efficiently in the Ednrb-deficient hindgut as did wild-type NCSCs. These results demonstrate intrinsic differences in the migratory properties and developmental potentials of regionally distinct NCSCs, indicating that it is critical to match the physiological properties of neural stem cells to the goals of proposed cell therapies.
Mosher
Jack T
JT
Department of Internal Medicine, Center for Stem Cell Biology, Howard Hughes Medical Institute, 3435 Life Sciences Institute, 210 Washtenaw Avenue, Ann Arbor, MI 48109, USA.
Yeager
Kelly J
KJ
Kruger
Genevieve M
GM
Joseph
Nancy M
NM
Hutchin
Mark E
ME
Dlugosz
Andrzej A
AA
Morrison
Sean J
SJ
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002478:Cells, Cultured; D002642:Chick Embryo; D017931:DNA Primers; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology*; D017615:Enteric Nervous System / Q000166:cytology / Q000196:embryology*; D005260:Female; D041981:Gastrointestinal Tract / Q000166:cytology; D006627:Hirschsprung Disease / Q000628:therapy*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008544:Melanocytes / Q000166:cytology; D009432:Neural Crest / Q000166:cytology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D017466:Receptors, Endothelin / Q000378:metabolism; D012584:Sciatic Nerve / Q000166:cytology; D033581:Stem Cell Transplantation
D017931:DNA Primers; D017466:Receptors, Endothelin