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Future Aspect

  • Sukhada Bhave
  • Ryo HottaEmail author
Chapter

Abstract

Overall outcome of Hirschsprung disease (HSCR) remain inadequate, and the treatment options for severe forms are limited to palliative interventions. Advances in molecular biology and genetics have led to development of cellular therapy for a potential curative treatment for HSCR. The field of cell therapies for HSCR has seen tremendous progress in recent years. A variety of sources for neural progenitor cells have been identified ranging from adult tissue-derived cells (endogenous enteric nervous system (ENS)-derived enteric neural progenitors (ENPCs)) to pluripotent stem cells (embryonic stem (ES) cells and induced pluripotent stem (iPS) cells). Key recent advances include reports of the efficient derivation and cultivation of ENPCs from either endogenous ENS or pluripotent stem cells and their further differentiation into functional enteric neurons in vitro. Following successful transplantation of these ENPCs into colon of mice with enteric neuropathies, including HSCR in vivo, functional integration into host enteric circuitry and rescued mortality of recipient mice have been achieved. A number of key challenges remain, however, before effective clinical application. These include the need to better understand the condition of aganglionic colon to accept transplanted cells, to optimize/manipulate cellular potential to maximize the success of cellular treatment, and to determine the long-term safety and efficacy of cell therapy. Nonetheless, the impressive recent progress raises further hope for the imminent use of cell transplantation as an effective therapy for HSCR.

Keywords

Hirschsprung disease Cell therapy Enteric neural progenitor cells Pluripotent stem cells Cell transplantation 

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© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Department of Pediatric Surgery, Massachusetts General HospitalHarvard Medical SchoolBostonUSA

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