Histochemistry and Cell Biology

, Volume 143, Issue 4, pp 397–410 | Cite as

Vascular and neural stem cells in the gut: do they need each other?

  • Sandra Schrenk
  • Anne Schuster
  • Markus Klotz
  • Franziska Schleser
  • Jonathan Lake
  • Robert O. Heuckeroth
  • Yoo-Jin Kim
  • Matthias W. Laschke
  • Michael D. Menger
  • Karl-Herbert SchäferEmail author
Original Paper


Enteric neurons and blood vessels form intricate networks throughout the gastrointestinal tract. To support the hypothesis of a possible interaction of both networks, we investigated whether primary mesenteric vascular cells (MVCs) and enteric nervous system (ENS)-derived cells (ENSc) depend on each other using two- and three-dimensional in vitro assays. In a confrontation assay, both cell types migrated in a target-oriented manner towards each other. The migration of MVCs was significantly increased when cultured in ENSc-conditioned medium. Co-cultures of ENSc with MVCs resulted in an improved ENSc proliferation and differentiation. Moreover, we analysed the formation of the vascular and nervous system in developing mice guts. It was found that the patterning of newly formed microvessels and neural stem cells, as confirmed by nestin and SOX2 stainings, is highly correlated in all parts of the developing gut. In particular in the distal colon, nestin/SOX2-positive cells were found in the tissues adjacent to the capillaries and in the capillaries themselves. Finally, in order to provide evidences for a mutual interaction between endothelial and neural cells, the vascular patterns of a RET(−/−) knockout mouse model as well as human Hirschsprung’s cases were analysed. In the distal colon of postnatal RET(−/−) knockout mice, the vascular and neural networks were similarly disrupted. In aganglionic zones of Hirschsprung’s patients, the microvascular density was significantly increased compared with the ganglionic zone within the submucosa. Taken together, these findings indicate a strong interaction between the enteric nervous and vascular system.


Enteric nervous system Mesenteric vascular cells Hirschsprung’s disease RET(−/−) knockout Neurovascular interaction 



Many thanks to Tanja Schwab for her support with cell cultures, Dr. Claudia Scheuer from the Institute of Clinical and Experimental Surgery, University of Saarland, for assistance with migration assays, Dr. Yvonne Schwarz from the group of Prof. Dr. Dieter Bruns, University clinic Homburg, for the help with confocal microscopy and Dr. Cornelia Hagl for proof reading the manuscript.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Sandra Schrenk
    • 1
  • Anne Schuster
    • 1
  • Markus Klotz
    • 1
  • Franziska Schleser
    • 1
  • Jonathan Lake
    • 2
  • Robert O. Heuckeroth
    • 3
  • Yoo-Jin Kim
    • 4
  • Matthias W. Laschke
    • 5
  • Michael D. Menger
    • 5
  • Karl-Herbert Schäfer
    • 1
    • 6
    Email author
  1. 1.Department of Computer Sciences and Microsystem TechnologyUniversity of Applied Sciences KaiserslauternZweibrückenGermany
  2. 2.Department of Pediatrics and Developmental BiologyWashington University School of MedicineSt. LouisUSA
  3. 3.Abramson Research CenterThe Children’s Hospital of PhiladelphiaPhiladelphiaUSA
  4. 4.Institute for PathologyUniversity of SaarlandHomburg/SaarGermany
  5. 5.Institute for Clinical and Experimental SurgeryUniversity of SaarlandHomburg/SaarGermany
  6. 6.Clinic of Pediatric SurgeryMedical Faculty Mannheim, University of HeidelbergMannheimGermany

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