Recent developments in cell-based ENS regeneration – a short review

Obermayr, Florian; Seitz, Guido

doi:10.1515/iss-2018-0005

Cited by 6 publications

(6 citation statements)

References 50 publications

(72 reference statements)

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“…In mammalian HSCR models a lot of progress has been made in optimizing transplantation therapy. However, there are still several limitations to overcome such as, limited migration of transplanted cells along the gut, requirement of very high numbers of cells and the integration in the endogenous ENS network [reviewed in: Obermayr and Seitz ( 2018 )]. Combining transplantation with the addition of chemical compounds that stimulate ENS development or make the ENS environment more favorable, could significantly improve transplantation outcomes (Lui et al, 2018 ; Zhao et al, 2020 ).…”

Section: Identification Of Drugs That Stimulate Ens Developmentmentioning

confidence: 99%

Zebrafish: A Model Organism for Studying Enteric Nervous System Development and Disease

Kuil¹,

Chauhan²,

Cheng³

et al. 2021

Front. Cell Dev. Biol.

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The Enteric Nervous System (ENS) is a large network of enteric neurons and glia that regulates various processes in the gastrointestinal tract including motility, local blood flow, mucosal transport and secretion. The ENS is derived from stem cells coming from the neural crest that migrate into and along the primitive gut. Defects in ENS establishment cause enteric neuropathies, including Hirschsprung disease (HSCR), which is characterized by an absence of enteric neural crest cells in the distal part of the colon. In this review, we discuss the use of zebrafish as a model organism to study the development of the ENS. The accessibility of the rapidly developing gut in zebrafish embryos and larvae, enables in vivo visualization of ENS development, peristalsis and gut transit. These properties make the zebrafish a highly suitable model to bring new insights into ENS development, as well as in HSCR pathogenesis. Zebrafish have already proven fruitful in studying ENS functionality and in the validation of novel HSCR risk genes. With the rapid advancements in gene editing techniques and their unique properties, research using zebrafish as a disease model, will further increase our understanding on the genetics underlying HSCR, as well as possible treatment options for this disease.

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Section: Identification Of Drugs That Stimulate Ens Developmentmentioning

confidence: 99%

Zebrafish: A Model Organism for Studying Enteric Nervous System Development and Disease

Kuil¹,

Chauhan²,

Cheng³

et al. 2021

Front. Cell Dev. Biol.

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“…However, this raises a question; what is the best source of these ENCCs? Depending on the source of ENCCs, they may be iPSC, ESCs, or native ENCCs [29]. To avoid use immunosuppression, the use of autologous-derived ENCCs would be the desired approach clinically.…”

Section: Discussionmentioning

confidence: 99%

Differentiation of enteric neural crest cells transplanted from SOX10-Venus mouse embryonic stem cells into the gut of the endothelin receptor B null mouse model

et al. 2022

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PurposeFailure of enteric neural crest-derived cells (ENCCs) to correctly colonize the embryonic gut results in Hirschsprung's disease (HD). Embryonic stem cells (ESCs) have the potential to differentiate into all tissue-speci c cells and lineages, including ENCCs. We investigated the cellular differentiation of ESCs from Sox10-Venus + mice into both control and endothelin receptor-B knockout (Ednrb KO) mouse gut to assess each region. MethodsWe established ESCs from Sox10-Venus + mice. These cells were cultured for two days, then selected and co-cultured with either a dissociated control or Sox10-Venus -Ednrb KO mouse gut (both small intestine and colon) on embryonic day (E) 13.5. Four days later, cells were immunolabeled for Tuj1 and visualized using confocal microscopy. ResultsConfocal microscopy revealed that transplanted Sox10-Venus + cells from ESCs migrated extensively within the host gut. Moreover, Tuj1-positive neurites were detected in the transplanted ESCs. Tuj1 expression was signi cantly decreased in aganglionic HD colon compared to controls (p<0.05) and the HD small intestine (p<0.05). ConclusionsThis study demonstrated that an appropriate host environment is crucial for normal and complete colonization of the gut. Further investigations are required to con rm whether modifying this environment can improve the results of this model.

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“…Nevertheless, before dwelling into those issues, we first must outline the therapeutic scheme that HSCR research tries to implement. The envisaged therapeutic approaches could be categorized according to the source of ENCC: induced pluripotent stem cell (iPSC), embryonic stem cell (ESC), or native ENCC [38]. In the iPSC-derived ENCC implantation method (Fig.…”

Section: Approaches and Cell Sourcementioning

confidence: 99%

“…The envisaged therapeutic approaches could be categorized according to the source of ENCC: induced pluripotent stem cell (iPSC), embryonic stem cell (ESC), or native ENCC [ 38 ]. In the iPSC-derived ENCC implantation method (Fig.…”

Section: Cell-based Therapymentioning

confidence: 99%

“…This fail-safe measure acts as a last resort in case of unexpected severe adverse reactions when utilizing ESC or iPSC-induced ENCC [ 48 , 49 ]. In addition to the tumorigenesis risk, the use of ESC-derived ENCC for allogeneic transplantation would require administering life-long immunosuppressive agents to avoid rejection and graft versus host disease [ 38 ], which might be even more harmful given the repeated bouts of enterocolitis in HSCR. This point stands in the way of attempting to recruit universal iPSC donors as well.…”

Section: Cell-based Therapymentioning

confidence: 99%

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Stem cell-based therapy for hirschsprung disease, do we have the guts to treat?

Alhawaj

2021

Gene Ther

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Hirschsprung disease (HSCR) is a congenital anomaly of the colon that results from failure of enteric nervous system formation, leading to a constricted dysfunctional segment of the colon with variable lengths, and necessitating surgical intervention. The underlying pathophysiology includes a defect in neural crest cells migration, proliferation and differentiation, which are partially explained by identified genetic and epigenetic alterations. Despite the high success rate of the curative surgeries, they are associated with significant adverse outcomes such as enterocolitis, fecal soiling, and chronic constipation. In addition, some patients suffer from extensive lethal variants of the disease, all of which justify the need for an alternative cure. During the last 5 years, there has been considerable progress in HSCR stem cell-based therapy research. However, many major issues remain unsolved. This review will provide concise background information on HSCR, outline the future approaches of stem cell-based HSCR therapy, review recent key publications, discuss technical and ethical challenges the field faces prior to clinical translation, and tackle such challenges by proposing solutions and evaluating existing approaches to progress further.

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Recent developments in cell-based ENS regeneration – a short review

Cited by 6 publications

References 50 publications

Zebrafish: A Model Organism for Studying Enteric Nervous System Development and Disease

Zebrafish: A Model Organism for Studying Enteric Nervous System Development and Disease

Differentiation of enteric neural crest cells transplanted from SOX10-Venus mouse embryonic stem cells into the gut of the endothelin receptor B null mouse model

Stem cell-based therapy for hirschsprung disease, do we have the guts to treat?

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