Elsevier

Developmental Biology

Volume 417, Issue 2, 15 September 2016, Pages 229-251
Developmental Biology

White paper on guidelines concerning enteric nervous system stem cell therapy for enteric neuropathies

https://doi.org/10.1016/j.ydbio.2016.04.001Get rights and content
Under a Creative Commons license
open access

Highlights

  • New treatments are sought for diseases affecting the enteric nervous system.

  • Stem cells could be transplanted into the gut to repair the enteric nervous system.

  • Experts give views on optimal stem cell therapy approaches for enteric neuropathies.

Abstract

Over the last 20 years, there has been increasing focus on the development of novel stem cell based therapies for the treatment of disorders and diseases affecting the enteric nervous system (ENS) of the gastrointestinal tract (so-called enteric neuropathies). Here, the idea is that ENS progenitor/stem cells could be transplanted into the gut wall to replace the damaged or absent neurons and glia of the ENS. This White Paper sets out experts’ views on the commonly used methods and approaches to identify, isolate, purify, expand and optimize ENS stem cells, transplant them into the bowel, and assess transplant success, including restoration of gut function. We also highlight obstacles that must be overcome in order to progress from successful preclinical studies in animal models to ENS stem cell therapies in the clinic.

Keywords

Enteric nervous system
Enteric neuropathies
Stem cells
Cell replacement therapy
Hirschsprung disease

Cited by (0)

Authorship note. AMG, DFN, LS, KHS, MM, RH, HMY, PWA and NT are lead authors on Introduction, 1 What are the target diseases for stem cell transplantation?, 1.1 Hirschsprung disease (HSCR), 1.2 Esophageal achalasia, 1.3 Gastroparesis, 1.4 Hypertrophic pyloric stenosis, 1.5 Chronic intestinal pseudo-obstruction (CIPO), 1.6 Neurogenic constipation and age-related loss of enteric neurons, 1.7 Chagas disease, 1.8 Other enteric neuropathies, 1.9 Phenotyping and genotyping of enteric neuropathies, 1.10 Conclusion, 1.10 Conclusion, 2.1 Cell, tissue and organ culture models for ENS formation, 2.1.1 Models of cells with ENS-forming competence, 2.1.2 Models of the bowel with enteric neuropathy, 2.1.3 Cells with ENS-forming competence, and affected bowel: models that bring the two together, 2.2 Whole animal models of ENS pathologies, 2.2.1 Rodent models, 2.2.2 Avian and Fish models, 2.2.3 Porcine models, 2.2.4 Chemically-induced models, 2.3 Conclusions, 3 What is the optimal source of stem cells for enteric neuronal replacement?, 3.1 Enteric nervous system neural stem/progenitor cells, 3.2 Non-ENS neural stem/progenitor cells, 3.3 Central nervous system (CNS) neural stem cells, 3.4 Pluripotent stem cells, 3.5 Other neural crest-derived stem cells sources, 4 Identifying, selecting, harvesting and optimizing isolation of gut-derived ENS progenitors/stem cells, 4.1 Optimizing, propagating, and priming stem cells prior to transplantation, 4.2 Conclusions, 5 How are “neurospheres”, and the neural progenitors within them, best characterized?, 5.1 Characterisation of neurosphere-like bodies (NLBs) from animal models, 5.2 Characterisation of human NLBs, 5.3 What can the ENS field learn from the CNS field concerning neurosphere characterization?, 6 What is the best way to deliver stem cells to the gut?, 6.1 Injection of cell suspension into the gut wall, 6.1.1 Seromuscular approach, 6.1.2 Intraluminal approach (Endoscopic approach), 6.2 Implantation of neurospheres into the gut wall, 6.3 Serosal application, 6.4 Intraperitoneal injection, 6.5 Vascular approach, 7 How do we measure cell transplantation success?, 7.1 Animal models, 7.2 Human patients with enteric neuropathies, 8 How can cell safety be assessed?, 9 Conclusions: the prospect of human trials.