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Stem Cell Therapy for Enteric Neuropathies

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Hirschsprung's Disease and Allied Disorders

Abstract

Enteric neuropathies, such as Hirschsprung disease (HSCR), comprise a number of severe diseases of the enteric nervous system (ENS) of the gastrointestinal (GI) tract with, as yet, no cures. The replacement of absent or diseased enteric neurons via stem cell transplantation directly into diseased gut represents a novel, curative therapy. This idea is supported by over two decades of preclinical research, carried out mainly in mice, demonstrating that neural crest-derived stem cells can be isolated from the gut, expanded in culture, and transplanted into gut in vivo where they migrate, proliferate, differentiate, and become functionally active. Here, we review some of the learnings from these studies, outlining the diseases potentially amenable to stem cell replacement therapy, the animals used to model disease, the different types of stem cells that could be used for therapy, the methodologies developed to prepare and deliver stem cells to the gut, and cell safety considerations. With the significant progress that has already been made by the field, the aim of developing a curative stem cell therapy for devastating diseases of the enteric nervous system is rapidly approaching reality.

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References

  1. Almond S, Lindley RM, Kenny SE, Connell MG, Edgar DH. Characterisation and transplantation of enteric nervous system progenitor cells. Gut. 2007;56:489–96.

    Article  Google Scholar 

  2. Amiel J, Sproat-Emison E, Garcia-Barcelo M, Lantieri F, Burzynski G, Borrego S, Pelet A, Arnold S, Miao X, Griseri P, Brooks AS, Antinolo G, de Pontual L, Clement-Ziza M, Munnich A, Kashuk C, West K, Wong KK, Lyonnet S, Chakravarti A, Tam PK, Ceccherini I, Hofstra RM, Fernandez R, Hirschsprung Disease C. Hirschsprung disease, associated syndromes and genetics: a review. J Med Genet. 2008;45:1–14.

    Article  CAS  Google Scholar 

  3. Anitha M, Joseph I, Ding X, Torre ER, Sawchuk MA, Mwangi S, Hochman S, Sitaraman SV, Anania F, Srinivasan S. Characterization of fetal and postnatal enteric neuronal cell lines with improvement in intestinal neural function. Gastroenterology. 2008;134:1424–35.

    Article  CAS  Google Scholar 

  4. Asai N, Fukuda T, Wu Z, Enomoto A, Pachnis V, Takahashi M, Costantini F. Targeted mutation of serine 697 in the Ret tyrosine kinase causes migration defect of enteric neural crest cells. Development. 2006;133:4507–16.

    Article  CAS  Google Scholar 

  5. Attie T, Pelet A, Edery P, Eng C, Mulligan LM, Amiel J, Boutrand L, Beldjord C, Nihoul-Fekete C, Munnich A, et al. Diversity of RET proto-oncogene mutations in familial and sporadic Hirschsprung disease. Hum Mol Genet. 1995;4:1381–6.

    Article  CAS  Google Scholar 

  6. Avery S, Hirst AJ, Baker D, Lim CY, Alagaratnam S, Skotheim RI, Lothe RA, Pera MF, Colman A, Robson P, Andrews PW, Knowles BB. BCL-XL mediates the strong selective advantage of a 20q11.21 amplification commonly found in human embryonic stem cell cultures. Stem Cell Reports. 2013;1:379–86.

    Article  CAS  Google Scholar 

  7. Baker D, Hirst AJ, Gokhale PJ, Juarez MA, Williams S, Wheeler M, Bean K, Allison TF, Moore HD, Andrews PW, Barbaric I. Detecting genetic mosaicism in cultures of human pluripotent stem cells. Stem Cell Reports. 2016;7:998–1012.

    Article  CAS  Google Scholar 

  8. Baker DE, Harrison NJ, Maltby E, Smith K, Moore HD, Shaw PJ, Heath PR, Holden H, Andrews PW. Adaptation to culture of human embryonic stem cells and oncogenesis in vivo. Nat Biotechnol. 2007;25:207–15.

    Article  CAS  Google Scholar 

  9. Barlow A, de Graaff E, Pachnis V. Enteric nervous system progenitors are coordinately controlled by the G protein-coupled receptor EDNRB and the receptor tyrosine kinase RET. Neuron. 2003;40:905–16.

    Article  CAS  Google Scholar 

  10. Binder E, Natarajan D, Cooper J, Kronfli R, Cananzi M, Delalande JM, McCann C, Burns AJ, Thapar N. Enteric neurospheres are not specific to neural crest cultures: implications for neural stem cell therapies. PLoS One. 2015;10:e0119467.

    Article  Google Scholar 

  11. Bixby S, Kruger GM, Mosher JT, Joseph NM, Morrison SJ. Cell-intrinsic differences between stem cells from different regions of the peripheral nervous system regulate the generation of neural diversity. Neuron. 2002;35:643–56.

    Article  CAS  Google Scholar 

  12. Bondurand N, Natarajan D, Thapar N, Atkins C, Pachnis V. Neuron and glia generating progenitors of the mammalian enteric nervous system isolated from foetal and postnatal gut cultures. Development. 2003;130:6387–400.

    Article  CAS  Google Scholar 

  13. Burns AJ, Goldstein AM, Newgreen DF, Stamp L, Schafer KH, Metzger M, Hotta R, Young HM, Andrews PW, Thapar N, Belkind-Gerson J, Bondurand N, Bornstein JC, Chan WY, Cheah K, Gershon MD, Heuckeroth RO, Hofstra RM, Just L, Kapur RP, King SK, McCann CJ, Nagy N, Ngan E, Obermayr F, Pachnis V, Pasricha PJ, Sham MH, Tam P, Vanden Berghe P. White paper on guidelines concerning enteric nervous system stem cell therapy for enteric neuropathies. Dev Biol. 2016;417:229–51.

    Article  CAS  Google Scholar 

  14. Burns AJ, Thapar N. Neural stem cell therapies for enteric nervous system disorders. Nat Rev Gastroenterol Hepatol. 2014;11:317–28.

    Article  Google Scholar 

  15. Burzynski G, Shepherd IT, Enomoto H. Genetic model system studies of the development of the enteric nervous system, gut motility and Hirschsprung’s disease. Neurogastroenterol Motil. 2009;21:113–27.

    Article  CAS  Google Scholar 

  16. Cheng LS, Hotta R, Graham HK, Belkind-Gerson J, Nagy N, Goldstein AM. Postnatal human enteric neuronal progenitors can migrate, differentiate, and proliferate in embryonic and postnatal aganglionic gut environments. Pediatr Res. 2017;81:838–46.

    Article  CAS  Google Scholar 

  17. Cheng LS, Hotta R, Graham HK, Nagy N, Goldstein AM, Belkind-Gerson J. Endoscopic delivery of enteric neural stem cells to treat Hirschsprung disease. Neurogastroenterol Motil. 2015;27:1509–14.

    Article  CAS  Google Scholar 

  18. Cooper JE, McCann CJ, Natarajan D, Choudhury S, Boesmans W, Delalande JM, Vanden Berghe P, Burns AJ, Thapar N. In vivo transplantation of enteric neural crest cells into mouse gut; engraftment, functional integration and long-term safety. PLoS One. 2016;11:e0147989.

    Article  Google Scholar 

  19. Cooper JE, Natarajan D, McCann CJ, Choudhury S, Godwin H, Burns AJ, Thapar N. In vivo transplantation of fetal human gut-derived enteric neural crest cells. Neurogastroenterol Motil. 2017;29(1) https://doi.org/10.1111/nmo.12900.

    Article  Google Scholar 

  20. Dang R, Torigoe D, Suzuki S, Kikkawa Y, Moritoh K, Sasaki N, Agui T. Genetic background strongly modifies the severity of symptoms of Hirschsprung disease, but not hearing loss in rats carrying Ednrb(sl) mutations. PLoS One. 2011;6:e24086.

    Article  CAS  Google Scholar 

  21. Dettmann HM, Zhang Y, Wronna N, Kraushaar U, Guenther E, Mohr R, Neckel PH, Mack A, Fuchs J, Just L, Obermayr F. Isolation, expansion and transplantation of postnatal murine progenitor cells of the enteric nervous system. PLoS One. 2014;9:e97792.

    Article  Google Scholar 

  22. Draper JS, Smith K, Gokhale P, Moore HD, Maltby E, Johnson J, Meisner L, Zwaka TP, Thomson JA, Andrews PW. Recurrent gain of chromosomes 17q and 12 in cultured human embryonic stem cells. Nat Biotechnol. 2004;22:53–4.

    Article  CAS  Google Scholar 

  23. Fattahi F, Steinbeck JA, Kriks S, Tchieu J, Zimmer B, Kishinevsky S, Zeltner N, Mica Y, El-Nachef W, Zhao H, de Stanchina E, Gershon MD, Grikscheit TC, Chen S, Studer L. Deriving human ENS lineages for cell therapy and drug discovery in Hirschsprung disease. Nature. 2016;531:105–9.

    Article  CAS  Google Scholar 

  24. Findlay Q, Yap KK, Bergner AJ, Young HM, Stamp LA. Enteric neural progenitors are more efficient than brain-derived progenitors at generating neurons in the colon. Am J Physiol Gastrointest Liver Physiol. 2014;307:G741–8.

    Article  CAS  Google Scholar 

  25. Fujimura T, Shibata S, Shimojima N, Morikawa Y, Okano H, Kuroda T. Fluorescence visualization of the enteric nervous network in a chemically induced aganglionosis model. PLoS One. 2016;11:e0150579.

    Article  Google Scholar 

  26. Fujiwara N, Miyahara K, Nakazawa-Tanaka N, Akazawa C, Yamataka A. Altered differentiation of enteric neural crest-derived cells from endothelin receptor-B null mouse model of Hirschsprung’s disease. Pediatr Surg Int. 2016;32:1095–101.

    Article  Google Scholar 

  27. Furuzawa-Carballeda J, Torres-Landa S, Valdovinos MA, Coss-Adame E, Martin Del Campo LA, Torres-Villalobos G. New insights into the pathophysiology of achalasia and implications for future treatment. World J Gastroenterol. 2016;22:7892–907.

    Article  CAS  Google Scholar 

  28. Goldring CE, Duffy PA, Benvenisty N, Andrews PW, Ben-David U, Eakins R, French N, Hanley NA, Kelly L, Kitteringham NR, Kurth J, Ladenheim D, Laverty H, McBlane J, Narayanan G, Patel S, Reinhardt J, Rossi A, Sharpe M, Park BK. Assessing the safety of stem cell therapeutics. Cell Stem Cell. 2011;8:618–28.

    Article  CAS  Google Scholar 

  29. Goldstein AM, Thapar N, Karunaratne TB, De Giorgio R. Clinical aspects of neurointestinal disease: pathophysiology, diagnosis, and treatment. Dev Biol. 2016;417:217–28.

    Article  CAS  Google Scholar 

  30. Grover M, Farrugia G, Lurken MS, Bernard CE, Faussone-Pellegrini MS, Smyrk TC, Parkman HP, Abell TL, Snape WJ, Hasler WL, Unalp-Arida A, Nguyen L, Koch KL, Calles J, Lee L, Tonascia J, Hamilton FA, Pasricha PJ, Consortium NGCR. Cellular changes in diabetic and idiopathic gastroparesis. Gastroenterology. 2011;140(1575–1585):e1578.

    Google Scholar 

  31. Hackland JOS, Frith TJR, Thompson O, Marin Navarro A, Garcia-Castro MI, Unger C, Andrews PW. Top-down inhibition of BMP signaling enables robust induction of hPSCs into neural crest in fully defined, xeno-free conditions. Stem Cell Reports. 2017;9:1043–52.

    Article  CAS  Google Scholar 

  32. Heanue TA, Pachnis V. Prospective identification and isolation of enteric nervous system progenitors using Sox2. Stem Cells. 2011;29:128–40.

    Article  CAS  Google Scholar 

  33. Hetz S, Acikgoez A, Voss U, Nieber K, Holland H, Hegewald C, Till H, Metzger R, Metzger M. In vivo transplantation of neurosphere-like bodies derived from the human postnatal and adult enteric nervous system: a pilot study. PLoS One. 2014;9:e93605.

    Article  Google Scholar 

  34. Hotta R, Cheng L, Graham HK, Nagy N, Belkind-Gerson J, Mattheolabakis G, Amiji MM, Goldstein AM. Delivery of enteric neural progenitors with 5-HT4 agonist-loaded nanoparticles and thermosensitive hydrogel enhances cell proliferation and differentiation following transplantation in vivo. Biomaterials. 2016a;88:1–11.

    Article  CAS  Google Scholar 

  35. Hotta R, Cheng LS, Graham HK, Pan W, Nagy N, Belkind-Gerson J, Goldstein AM. Isogenic enteric neural progenitor cells can replace missing neurons and glia in mice with Hirschsprung disease. Neurogastroenterol Motil. 2016b;28:498–512.

    Article  CAS  Google Scholar 

  36. Hotta R, Stamp LA, Foong JP, McConnell SN, Bergner AJ, Anderson RB, Enomoto H, Newgreen DF, Obermayr F, Furness JB, Young HM. Transplanted progenitors generate functional enteric neurons in the postnatal colon. J Clin Invest. 2013;123:1182–91.

    Article  CAS  Google Scholar 

  37. International Stem Cell Initiative, Adewumi O, Aflatoonian B, Ahrlund-Richter L, Amit M, Andrews PW, Beighton G, Bello PA, Benvenisty N, Berry LS, Bevan S, Blum B, Brooking J, Chen KG, Choo AB, Churchill GA, Corbel M, Damjanov I, Draper JS, Dvorak P, Emanuelsson K, Fleck RA, Ford A, Gertow K, Gertsenstein M, Gokhale PJ, Hamilton RS, Hampl A, Healy LE, Hovatta O, Hyllner J, Imreh MP, Itskovitz-Eldor J, Jackson J, Johnson JL, Jones M, Kee K, King BL, Knowles BB, Lako M, Lebrin F, Mallon BS, Manning D, Mayshar Y, McKay RD, Michalska AE, Mikkola M, Mileikovsky M, Minger SL, Moore HD, Mummery CL, Nagy A, Nakatsuji N, O'Brien CM, Oh SK, Olsson C, Otonkoski T, Park KY, Passier R, Patel H, Patel M, Pedersen R, Pera MF, Piekarczyk MS, Pera RA, Reubinoff BE, Robins AJ, Rossant J, Rugg-Gunn P, Schulz TC, Semb H, Sherrer ES, Siemen H, Stacey GN, Stojkovic M, Suemori H, Szatkiewicz J, Turetsky T, Tuuri T, van den Brink S, Vintersten K, Vuoristo S, Ward D, Weaver TA, Young LA, Zhang W. Characterization of human embryonic stem cell lines by the International Stem Cell Initiative. Nat Biotechnol. 2007;25:803–16.

    Article  Google Scholar 

  38. International Stem Cell Initiative, Amps K, Andrews PW, Anyfantis G, Armstrong L, Avery S, Baharvand H, Baker J, Baker D, Munoz MB, Beil S, Benvenisty N, Ben-Yosef D, Biancotti JC, Bosman A, Brena RM, Brison D, Caisander G, Camarasa MV, Chen J, Chiao E, Choi YM, Choo AB, Collins D, Colman A, Crook JM, Daley GQ, Dalton A, De Sousa PA, Denning C, Downie J, Dvorak P, Montgomery KD, Feki A, Ford A, Fox V, Fraga AM, Frumkin T, Ge L, Gokhale PJ, Golan-Lev T, Gourabi H, Gropp M, Lu G, Hampl A, Harron K, Healy L, Herath W, Holm F, Hovatta O, Hyllner J, Inamdar MS, Irwanto AK, Ishii T, Jaconi M, Jin Y, Kimber S, Kiselev S, Knowles BB, Kopper O, Kukharenko V, Kuliev A, Lagarkova MA, Laird PW, Lako M, Laslett AL, Lavon N, Lee DR, Lee JE, Li C, Lim LS, Ludwig TE, Ma Y, Maltby E, Mateizel I, Mayshar Y, Mileikovsky M, Minger SL, Miyazaki T, Moon SY, Moore H, Mummery C, Nagy A, Nakatsuji N, Narwani K, Oh SK, Oh SK, Olson C, Otonkoski T, Pan F, Park IH, Pells S, Pera MF, Pereira LV, Qi O, Raj GS, Reubinoff B, Robins A, Robson P, Rossant J, Salekdeh GH, Schulz TC, Sermon K, Sheik Mohamed J, Shen H, Sherrer E, Sidhu K, Sivarajah S, Skottman H, Spits C, Stacey GN, Strehl R, Strelchenko N, Suemori H, Sun B, Suuronen R, Takahashi K, Tuuri T, Venu P, Verlinsky Y, Ward-van Oostwaard D, Weisenberger DJ, Wu Y, Yamanaka S, Young L, Zhou Q. Screening ethnically diverse human embryonic stem cells identifies a chromosome 20 minimal amplicon conferring growth advantage. Nat Biotechnol. 2011;29:1132–44.

    Article  Google Scholar 

  39. Iwashita T, Kruger GM, Pardal R, Kiel MJ, Morrison SJ. Hirschsprung disease is linked to defects in neural crest stem cell function. Science. 2003;301:972–6.

    Article  CAS  Google Scholar 

  40. Kruger GM, Mosher JT, Bixby S, Joseph N, Iwashita T, Morrison SJ. Neural crest stem cells persist in the adult gut but undergo changes in self-renewal, neuronal subtype potential, and factor responsiveness. Neuron. 2002;35:657–69.

    Article  CAS  Google Scholar 

  41. Kulkarni S, Zou B, Hanson J, Micci MA, Tiwari G, Becker L, Kaiser M, Xie XS, Pasricha PJ. Gut-derived factors promote neurogenesis of CNS-neural stem cells and nudge their differentiation to an enteric-like neuronal phenotype. Am J Physiol Gastrointest Liver Physiol. 2011;301:G644–55.

    Article  CAS  Google Scholar 

  42. Lai FP, Lau ST, Wong JK, Gui H, Wang RX, Zhou T, Lai WH, Tse HF, Tam PK, Garcia-Barcelo MM, Ngan ES. Correction of Hirschsprung-associated mutations in human induced pluripotent stem cells via clustered regularly interspaced short palindromic repeats/Cas9, restores neural crest cell function. Gastroenterology. 2017;153(139–153):e138.

    Google Scholar 

  43. Li W, Huang L, Zeng J, Lin W, Li K, Sun J, Huang W, Chen J, Wang G, Ke Q, Duan J, Lai X, Chen R, Liu M, Liu Y, Wang T, Yang X, Chen Y, Xia H, Xiang AP. Characterization and transplantation of enteric neural crest cells from human induced pluripotent stem cells. Mol Psychiatry. 2018;23:499–508.

    Article  CAS  Google Scholar 

  44. Lindley RM, Hawcutt DB, Connell MG, Almond SL, Vannucchi MG, Faussone-Pellegrini MS, Edgar DH, Kenny SE. Human and mouse enteric nervous system neurosphere transplants regulate the function of aganglionic embryonic distal colon. Gastroenterology. 2008;135(205–216):e206.

    Google Scholar 

  45. Liu MT, Kuan YH, Wang J, Hen R, Gershon MD. 5-HT4 receptor-mediated neuroprotection and neurogenesis in the enteric nervous system of adult mice. J Neurosci. 2009;29:9683–99.

    Article  CAS  Google Scholar 

  46. Liu W, Yue W, Wu R. Overexpression of Bcl-2 promotes survival and differentiation of neuroepithelial stem cells after transplantation into rat aganglionic colon. Stem Cell Res Ther. 2013;4:7.

    Article  CAS  Google Scholar 

  47. Martucciello G, Brizzolara A, Favre A, Lombardi L, Bocciardi R, Sanguineti M, Pini Prato A, Jasonni V. Neural crest neuroblasts can colonise aganglionic and ganglionic gut in vivo. Eur J Pediatr Surg. 2007;17:34–40.

    Article  CAS  Google Scholar 

  48. McCann CJ, Cooper JE, Natarajan D, Jevans B, Burnett LE, Burns AJ, Thapar N. Transplantation of enteric nervous system stem cells rescues nitric oxide synthase deficient mouse colon. Nat Commun. 2017;8:15937.

    Article  CAS  Google Scholar 

  49. McKeown SJ, Mohsenipour M, Bergner AJ, Young HM, Stamp LA. Exposure to GDNF enhances the ability of enteric neural progenitors to generate an enteric nervous system. Stem Cell Reports. 2017;8:476–88.

    Article  CAS  Google Scholar 

  50. Metzger M, Caldwell C, Barlow AJ, Burns AJ, Thapar N. Enteric nervous system stem cells derived from human gut mucosa for the treatment of aganglionic gut disorders. Gastroenterology. 2009;136(2214–2225):e2211–3.

    Google Scholar 

  51. Micci MA, Kahrig KM, Simmons RS, Sarna SK, Espejo-Navarro MR, Pasricha PJ. Neural stem cell transplantation in the stomach rescues gastric function in neuronal nitric oxide synthase-deficient mice. Gastroenterology. 2005a;129:1817–24.

    Article  CAS  Google Scholar 

  52. Micci MA, Learish RD, Li H, Abraham BP, Pasricha PJ. Neural stem cells express RET, produce nitric oxide, and survive transplantation in the gastrointestinal tract. Gastroenterology. 2001;121:757–66.

    Article  CAS  Google Scholar 

  53. Micci MA, Pattillo MT, Kahrig KM, Pasricha PJ. Caspase inhibition increases survival of neural stem cells in the gastrointestinal tract. Neurogastroenterol Motil. 2005b;17:557–64.

    Article  Google Scholar 

  54. Mosher JT, Yeager KJ, Kruger GM, Joseph NM, Hutchin ME, Dlugosz AA, Morrison SJ. Intrinsic differences among spatially distinct neural crest stem cells in terms of migratory properties, fate determination, and ability to colonize the enteric nervous system. Dev Biol. 2007;303:1–15.

    Article  CAS  Google Scholar 

  55. Natarajan D, Cooper J, Choudhury S, Delalande JM, McCann C, Howe SJ, Thapar N, Burns AJ. Lentiviral labeling of mouse and human enteric nervous system stem cells for regenerative medicine studies. Neurogastroenterol Motil. 2014;26:1513–8.

    Article  CAS  Google Scholar 

  56. Natarajan D, Grigoriou M, Marcos-Gutierrez CV, Atkins C, Pachnis V. Multipotential progenitors of the mammalian enteric nervous system capable of colonising aganglionic bowel in organ culture. Development. 1999;126:157–68.

    CAS  PubMed  Google Scholar 

  57. Nguyen HT, Geens M, Mertzanidou A, Jacobs K, Heirman C, Breckpot K, Spits C. Gain of 20q11.21 in human embryonic stem cells improves cell survival by increased expression of Bcl-xL. Mol Hum Reprod. 2014;20:168–77.

    Article  CAS  Google Scholar 

  58. Olariu V, Harrison NJ, Coca D, Gokhale PJ, Baker D, Billings S, Kadirkamanathan V, Andrews PW. Modeling the evolution of culture-adapted human embryonic stem cells. Stem Cell Res. 2010;4:50–6.

    Article  Google Scholar 

  59. Rollo BN, Zhang D, Stamp LA, Menheniott TR, Stathopoulos L, Denham M, Dottori M, King SK, Hutson JM, Newgreen DF. Enteric neural cells from hirschsprung disease patients form ganglia in autologous aneuronal colon. Cell Mol Gastroenterol Hepatol. 2016;2:92–109.

    Article  Google Scholar 

  60. Sato Y, Heuckeroth RO. Retinoic acid regulates murine enteric nervous system precursor proliferation, enhances neuronal precursor differentiation, and reduces neurite growth in vitro. Dev Biol. 2008;320:185–98.

    Article  CAS  Google Scholar 

  61. Schafer KH, Micci MA, Pasricha PJ. Neural stem cell transplantation in the enteric nervous system: roadmaps and roadblocks. Neurogastroenterol Motil. 2009;21:103–12.

    Article  Google Scholar 

  62. Schlieve CR, Fowler KL, Thornton M, Huang S, Hajjali I, Hou X, Grubbs B, Spence JR, Grikscheit TC. Neural crest cell implantation restores enteric nervous system function and alters the gastrointestinal transcriptome in human tissue-engineered small intestine. Stem Cell Reports. 2017;9:883–96.

    Article  CAS  Google Scholar 

  63. Stamp LA. Cell therapy for GI motility disorders: comparison of cell sources and proposed steps for treating Hirschsprung disease. Am J Physiol Gastrointest Liver Physiol. 2017;312:G348–54.

    Article  Google Scholar 

  64. Stamp LA, Gwynne RM, Foong JPP, Lomax AE, Hao MM, Kaplan DI, Reid CA, Petrou S, Allen AM, Bornstein JC, Young HM. Optogenetic demonstration of functional innervation of mouse colon by neurons derived from transplanted neural cells. Gastroenterology. 2017;152:1407–18.

    Article  Google Scholar 

  65. Stamp LA, Obermayr F, Pontell L, Young HM, Xie D, Croaker DH, Song ZM, Furness JB. Surgical intervention to rescue Hirschsprung disease in a rat model. J Neurogastroenterol Motil. 2015;21:552–9.

    Article  Google Scholar 

  66. Trounson A, DeWitt ND. Pluripotent stem cells progressing to the clinic. Nat Rev Mol Cell Biol. 2016;17:194–200.

    Article  CAS  Google Scholar 

  67. Tsai YH, Murakami N, Gariepy CE. Postnatal intestinal engraftment of prospectively selected enteric neural crest stem cells in a rat model of Hirschsprung disease. Neurogastroenterol Motil. 2011;23:362–9.

    Article  Google Scholar 

  68. Uesaka T, Nagashimada M, Yonemura S, Enomoto H. Diminished Ret expression compromises neuronal survival in the colon and causes intestinal aganglionosis in mice. J Clin Invest. 2008;118:1890–8.

    Article  CAS  Google Scholar 

  69. Wester T, Granstrom AL. Hirschsprung disease-Bowel function beyond childhood. Semin Pediatr Surg. 2017;26:322–7.

    Article  Google Scholar 

  70. Workman MJ, Mahe MM, Trisno S, Poling HM, Watson CL, Sundaram N, Chang CF, Schiesser J, Aubert P, Stanley EG, Elefanty AG, Miyaoka Y, Mandegar MA, Conklin BR, Neunlist M, Brugmann SA, Helmrath MA, Wells JM. Engineered human pluripotent-stem-cell-derived intestinal tissues with a functional enteric nervous system. Nat Med. 2017;23:49–59.

    Article  CAS  Google Scholar 

  71. Zimmer J, Puri P. Knockout mouse models of Hirschsprung’s disease. Pediatr Surg Int. 2015;31:787–94.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Stem Cells and Regenerative Medicine, UCL Great Ormond Street Institute of Child Health, London, UK

    Conor J. McCann, Nikhil Thapar & Alan J. Burns

  2. Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Allan M. Goldstein & Ryo Hotta

  3. Department of Clinical Genetics, Erasmus University Medical Centre, Rotterdam, The Netherlands

    Robert M. W. Hofstra & Alan J. Burns

  4. Takeda Pharmaceuticals International, Cambridge, MA, USA

    Alan J. Burns

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  1. Conor J. McCann
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  2. Allan M. Goldstein
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  3. Ryo Hotta
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  4. Nikhil Thapar
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  5. Robert M. W. Hofstra
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  6. Alan J. Burns
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Correspondence to Alan J. Burns .

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  1. National Children’s Research Centre, Our Lady’s Childrens Hospital, University College Dublin, Dublin, Ireland

    Prem Puri

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McCann, C.J., Goldstein, A.M., Hotta, R., Thapar, N., Hofstra, R.M.W., Burns, A.J. (2019). Stem Cell Therapy for Enteric Neuropathies. In: Puri, P. (eds) Hirschsprung's Disease and Allied Disorders. Springer, Cham. https://doi.org/10.1007/978-3-030-15647-3_8

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