PMID- 24699866
OWN - NLM
STAT- MEDLINE
DCOM- 20150202
LR  - 20240326
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 4
DP  - 2014
TI  - In vivo transplantation of neurosphere-like bodies derived from the human 
      postnatal and adult enteric nervous system: a pilot study.
PG  - e93605
LID - 10.1371/journal.pone.0093605 [doi]
LID - e93605
AB  - Recent advances in the in vitro characterization of human adult enteric neural 
      progenitor cells have opened new possibilities for cell-based therapies in 
      gastrointestinal motility disorders. However, whether these cells are able to 
      integrate within an in vivo gut environment is still unclear. In this study, we 
      transplanted neural progenitor-containing neurosphere-like bodies (NLBs) in a 
      mouse model of hypoganglionosis and analyzed cellular integration of NLB-derived 
      cell types and functional improvement. NLBs were propagated from postnatal and 
      adult human gut tissues. Cells were characterized by immunohistochemistry, 
      quantitative PCR and subtelomere fluorescence in situ hybridization (FISH). For 
      in vivo evaluation, the plexus of murine colon was damaged by the application of 
      cationic surfactant benzalkonium chloride which was followed by the 
      transplantation of NLBs in a fibrin matrix. After 4 weeks, grafted human cells 
      were visualized by combined in situ hybridization (Alu) and immunohistochemistry 
      (PGP9.5, GFAP, SMA). In addition, we determined nitric oxide synthase 
      (NOS)-positive neurons and measured hypertrophic effects in the ENS and 
      musculature. Contractility of treated guts was assessed in organ bath after 
      electrical field stimulation. NLBs could be reproducibly generated without any 
      signs of chromosomal alterations using subtelomere FISH. NLB-derived cells 
      integrated within the host tissue and showed expected differentiated phenotypes 
      i.e. enteric neurons, glia and smooth muscle-like cells following in vivo 
      transplantation. Our data suggest biological effects of the transplanted NLB 
      cells on tissue contractility, although robust statistical results could not be 
      obtained due to the small sample size. Further, it is unclear, which of the NLB 
      cell types including neural progenitors have direct restoring effects or, 
      alternatively may act via 'bystander' mechanisms in vivo. Our findings provide 
      further evidence that NLB transplantation can be considered as feasible tool to 
      improve ENS function in a variety of gastrointestinal disorders.
FAU - Hetz, Susan
AU  - Hetz S
AD  - Translational Centre for Regenerative Medicine, University of Leipzig, Leipzig, 
      Germany; Fraunhofer Institute for Cell Therapy and Immunology, Clinic-oriented 
      Therapy Assessment Unit, Leipzig, Germany.
FAU - Acikgoez, Ali
AU  - Acikgoez A
AD  - Department of General and Visceral Surgery, St. George's Hospital Leipzig, 
      Leipzig, Germany.
FAU - Voss, Ulrike
AU  - Voss U
AD  - Institute of Pharmacy, Pharmacology for Natural Sciences, University of Leipzig, 
      Leipzig, Germany.
FAU - Nieber, Karen
AU  - Nieber K
AD  - Institute of Pharmacy, Pharmacology for Natural Sciences, University of Leipzig, 
      Leipzig, Germany.
FAU - Holland, Heidrun
AU  - Holland H
AD  - Translational Centre for Regenerative Medicine, University of Leipzig, Leipzig, 
      Germany.
FAU - Hegewald, Cindy
AU  - Hegewald C
AD  - Translational Centre for Regenerative Medicine, University of Leipzig, Leipzig, 
      Germany.
FAU - Till, Holger
AU  - Till H
AD  - Department of Pediatric and Adolescent Surgery, Medical University of Graz, Graz, 
      Austria.
FAU - Metzger, Roman
AU  - Metzger R
AD  - Department of Pediatrics and Adolescent Medicine, Salzburg County Hospital, 
      Salzburg, Austria.
FAU - Metzger, Marco
AU  - Metzger M
AD  - Translational Centre for Regenerative Medicine, University of Leipzig, Leipzig, 
      Germany; Tissue Engineering and Regenerative Medicine, Fraunhofer IGB Project 
      Group: Regenerative Technologies for Oncology, University Hospital Wurzburg, 
      Wurzburg, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140403
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (DNA Primers)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Animals
MH  - Base Sequence
MH  - *Cell Transplantation
MH  - Child
MH  - DNA Primers
MH  - Enteric Nervous System/*cytology
MH  - Female
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Infant
MH  - Male
MH  - Mice
MH  - Middle Aged
MH  - Pilot Projects
MH  - Polymerase Chain Reaction
MH  - Young Adult
PMC - PMC3974735
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/04/05 06:00
MHDA- 2015/02/03 06:00
PMCR- 2014/04/03
CRDT- 2014/04/05 06:00
PHST- 2013/12/31 00:00 [received]
PHST- 2014/03/06 00:00 [accepted]
PHST- 2014/04/05 06:00 [entrez]
PHST- 2014/04/05 06:00 [pubmed]
PHST- 2015/02/03 06:00 [medline]
PHST- 2014/04/03 00:00 [pmc-release]
AID - PONE-D-13-55080 [pii]
AID - 10.1371/journal.pone.0093605 [doi]
PST - epublish
SO  - PLoS One. 2014 Apr 3;9(4):e93605. doi: 10.1371/journal.pone.0093605. eCollection 
      2014.