Neural stem cell transplantation in the enteric nervous system: roadmaps and roadblocks

Abstract  The enteric nervous system (ENS) is vulnerable to a variety of genetic, metabolic or environmental threats, resulting in clinical disorders characterized by loss or malfunction of neuronal elements. These disorders have been difficult to treat and there is much enthusiasm for novel therapies such as neural stem cell (NSC) transplantation to restore ENS function in diseased segments of the gut. Recent research has indicated the potential for a variety of innovative approaches to this effect using NSC obtained from the central nervous system (CNS) as well as gut derived enteric neuronal progenitors. The main goal of this review is to summarize the current status of NSC research as it applies to the ENS, delineate a roadmap for effective therapeutic strategies using NSC transplantation and point out the numerous challenges that lie ahead.

[1]  G. Biella,et al.  Setting the conditions for efficient, robust and reproducible generation of functionally active neurons from adult subventricular zone-derived neural stem cells , 2008, Cell Death and Differentiation.

[2]  G. Locke,et al.  Endoscopic "no hole" full-thickness biopsy of the stomach to detect myenteric ganglia. , 2008, Gastrointestinal endoscopy.

[3]  M. Vannucchi,et al.  Human and mouse enteric nervous system neurosphere transplants regulate the function of aganglionic embryonic distal colon. , 2008, Gastroenterology.

[4]  N. Chaverot,et al.  Molecular Mechanism of Systemic Delivery of Neural Precursor Cells to the Brain: Assembly of Brain Endothelial Apical Cups and Control of Transmigration by CD44 , 2008, Stem cells.

[5]  G. Locke,et al.  Evaluation of endoscopic approaches for deep gastric-muscle-wall biopsies: what works? , 2008, Gastrointestinal endoscopy.

[6]  Y. Gao,et al.  Neuroepithelial stem cells differentiate into neuronal phenotypes and improve intestinal motility recovery after transplantation in the aganglionic colon of the rat , 2007, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[7]  M. Fussenegger,et al.  RETRACTED: Autologous myoblasts and fibroblasts versus collagen for treatment of stress urinary incontinence in women: a randomised controlled trial , 2007, The Lancet.

[8]  P. Pasricha.  Desperately seeking serotonin... A commentary on the withdrawal of tegaserod and the state of drug development for functional and motility disorders. , 2007, Gastroenterology.

[9]  Y. Barde,et al.  Generation of a defined and uniform population of CNS progenitors and neurons from mouse embryonic stem cells , 2007, Nature Protocols.

[10]  R. Bocciardi,et al.  Neural crest neuroblasts can colonise aganglionic and ganglionic gut in vivo. , 2007, European journal of pediatric surgery : official journal of Austrian Association of Pediatric Surgery ... [et al] = Zeitschrift fur Kinderchirurgie.

[11]  M. Micci,et al.  Neural stem cells for the treatment of disorders of the enteric nervous system: Strategies and challenges , 2007, Developmental dynamics : an official publication of the American Association of Anatomists.

[12]  D. Edgar,et al.  Characterisation and transplantation of enteric nervous system progenitor cells , 2006, Gut.

[13]  S. Holland-Cunz,et al.  Isolation and cultivation of neuronal precursor cells from the developing human enteric nervous system as a tool for cell therapy in dysganglionosis , 2006, International Journal of Colorectal Disease.

[14]  R. Heuckeroth,et al.  Getting to the guts of enteric nervous system development , 2006, Development.

[15]  G. Martino,et al.  The therapeutic potential of neural stem cells , 2006, Nature Reviews Neuroscience.

[16]  P. Pasricha,et al.  Neural stem cell transplantation in the stomach rescues gastric function in neuronal nitric oxide synthase-deficient mice. , 2005, Gastroenterology.

[17]  F. Alpy,et al.  The expression pattern of laminin isoforms in Hirschsprung disease reveals a distal peripheral nerve differentiation. , 2005, Human pathology.

[18]  R. S. Goldstein,et al.  Generation of Peripheral Sensory and Sympathetic Neurons and Neural Crest Cells from Human Embryonic Stem Cells , 2005, Stem cells.

[19]  K. Kahrig,et al.  Caspase inhibition increases survival of neural stem cells in the gastrointestinal tract , 2005, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[20]  V. Ourednik,et al.  Graft/Host Relationships in the Developing and Regenerating CNS of Mammals , 2005, Annals of the New York Academy of Sciences.

[21]  G. Martino,et al.  Neural stem cells and their use as therapeutic tool in neurological disorders , 2005, Brain Research Reviews.

[22]  J. Belkind-Gerson,et al.  Cultured Nestin–Positive Cells from Postnatal Mouse Small Bowel Differentiate Ex Vivo into Neurons, Glia, and Smooth Muscle , 2004, Stem cells.

[23]  V. Staiger,et al.  Differentiation of mouse embryonic stem cells into a defined neuronal lineage , 2004, Nature Neuroscience.

[24]  M. Ochi,et al.  Intravenously injected neural progenitor cells of transgenic rats can migrate to the injured spinal cord and differentiate into neurons, astrocytes and oligodendrocytes , 2004, Neuroscience Letters.

[25]  Lia S. Campos,et al.  β1 integrins activate a MAPK signalling pathway in neural stem cells that contributes to their maintenance , 2004, Development.

[26]  M. Hanani.  Multiple myenteric networks in the human appendix , 2004, Autonomic Neuroscience.

[27]  C. Atkins,et al.  Neuron and glia generating progenitors of the mammalian enteric nervous system isolated from foetal and postnatal gut cultures , 2003, Development.

[28]  K. Schäfer,et al.  Differentiation of neurospheres from the enteric nervous system , 2003, Pediatric Surgery International.

[29]  K. Mizuseki,et al.  Generation of neural crest-derived peripheral neurons and floor plate cells from mouse and primate embryonic stem cells , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[30]  D. Lloyd,et al.  Location of stem cells for the enteric nervous system , 2002, Pediatric Surgery International.

[31]  S. Morrison,et al.  Cell-Intrinsic Differences between Stem Cells from Different Regions of the Peripheral Nervous System Regulate the Generation of Neural Diversity , 2002, Neuron.

[32]  S. Morrison,et al.  Neural Crest Stem Cells Persist in the Adult Gut but Undergo Changes in Self-Renewal, Neuronal Subtype Potential, and Factor Responsiveness , 2002, Neuron.

[33]  S. Schiffmann,et al.  Distribution of the intermediate filament nestin in the muscularis propria of the human gastrointestinal tract , 2002, Cell and Tissue Research.

[34]  Benjamin E. Reubinoff,et al.  Neural progenitors from human embryonic stem cells , 2001, Nature Biotechnology.

[35]  Hui Li,et al.  Neural stem cells express RET, produce nitric oxide, and survive transplantation in the gastrointestinal tract. , 2001, Gastroenterology.

[36]  Perry F. Bartlett,et al.  Purification of a pluripotent neural stem cell from the adult mouse brain , 2001, Nature.

[37]  D. O’Briain,et al.  Cell-adhesion molecules and fibroblast growth factor signalling in Hirschsprung's disease , 2001, Pediatric Surgery International.

[38]  A. Trounson,et al.  Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro , 2000, Nature Biotechnology.

[39]  H. Young,et al.  Expression of Ret‐, p75NTR‐, Phox2a‐, Phox2b‐, and tyrosine hydroxylase‐immunoreactivity by undifferentiated neural crest‐derived cells and different classes of enteric neurons in the embryonic mouse gut , 1999, Developmental dynamics : an official publication of the American Association of Anatomists.

[40]  H. Kuhn,et al.  Origins, functions, and potential of adult neural stem cells. , 1999, BioEssays : news and reviews in molecular, cellular and developmental biology.

[41]  C. Svendsen,et al.  Human Neural Stem Cells: Isolation, Expansion and Transplantation , 1999, Brain pathology.

[42]  E. Clarkson,et al.  Growth factors improve immediate survival of embryonic dopamine neurons after transplantation into rats , 1998, Brain Research.

[43]  P. Mestres,et al.  Human newborn and adult myenteric plexus grows in different patterns. , 1997, Cellular and molecular biology.

[44]  M. Gershon.  Genes and lineages in the formation of the enteric nervous system , 1997, Current Opinion in Neurobiology.

[45]  E. Parati,et al.  Multipotential stem cells from the adult mouse brain proliferate and self-renew in response to basic fibroblast growth factor , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[46]  J. Rosenstein.  Why Do Neural Transplants Survive? An Examination of Some Metabolic and Pathophysiological Considerations in Neural Transplantation , 1995, Experimental Neurology.

[47]  G. Owens,et al.  Programmed Cell Death in Developing Grafts of Fetal Substantia Nigra , 1994, Experimental Neurology.

[48]  R. McKay,et al.  Independent regulatory elements in the nestin gene direct transgene expression to neural stem cells or muscle precursors , 1994, Neuron.

[49]  T. P. Rothman,et al.  From neural crest to bowel: development of the enteric nervous system. , 1993, Journal of neurobiology.

[50]  R. McKay,et al.  CNS stem cells express a new class of intermediate filament protein , 1990, Cell.

[51]  J. Dungan.  Autologous myoblasts and fibroblasts versus collagen for treatment of stress urinary incontinence in women: a randomised controlled trial , 2008 .

[52]  A. Burns.  Migration of neural crest-derived enteric nervous system precursor cells to and within the gastrointestinal tract. , 2005, The International journal of developmental biology.

[53]  G. Plataniotis,et al.  Short-term preoperative radiotherapy is a safe approach for treatment of locally advanced rectal cancer , 2005, International Journal of Colorectal Disease.

[54]  E. Ekblad,et al.  Survival of neurons and interstitial cells of Cajal after autotransplantation of myenteric ganglia from small intestine in the lethal spotted mouse , 2000, Pediatric Surgery International.

[55]  C. Atkins,et al.  Multipotential progenitors of the mammalian enteric nervous system capable of colonising aganglionic bowel in organ culture. , 1999, Development.

[56]  C. Gambini,et al.  GDNF deficit in Hirschsprung's disease. , 1998, Journal of pediatric surgery.

[57]  M. Rao,et al.  A common neural progenitor for the CNS and PNS. , 1998, Developmental biology.

[58]  M. Bronner‐Fraser.  Origin of the avian neural crestt , 1995, Stem cells.

[59]  C. Olanow,et al.  The influence of donor age on the survival of solid and suspension intraparenchymal human embryonic nigral grafts. , 1995, Cell transplantation.