PMID- 26398705
OWN - NLM
STAT- MEDLINE
DCOM- 20160614
LR  - 20220330
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 9
DP  - 2015
TI  - The Role of Genetically Modified Mesenchymal Stem Cells in Urinary Bladder 
      Regeneration.
PG  - e0138643
LID - 10.1371/journal.pone.0138643 [doi]
LID - e0138643
AB  - Recent studies have demonstrated that mesenchymal stem cells (MSCs) combined with 
      CD34+ hematopoietic/stem progenitor cells (HSPCs) can function as surrogate 
      urinary bladder cells to synergistically promote multi-faceted bladder tissue 
      regeneration. However, the molecular pathways governing these events are unknown. 
      The pleiotropic effects of Wnt5a and Cyr61 are known to affect aspects of 
      hematopoiesis, angiogenesis, and muscle and nerve regeneration. Within this 
      study, the effects of Cyr61 and Wnt5a on bladder tissue regeneration were 
      evaluated by grafting scaffolds containing modified human bone marrow derived 
      MSCs. These cell lines were engineered to independently over-express Wnt5a or 
      Cyr61, or to exhibit reduced expression of Cyr61 within the context of a nude rat 
      bladder augmentation model. At 4 weeks post-surgery, data demonstrated increased 
      vessel number (~250 vs ~109 vessels/mm2) and bladder smooth muscle content (~42% 
      vs ~36%) in Cyr61OX (over-expressing) vs Cyr61KD (knock-down) groups. Muscle 
      content decreased to ~25% at 10 weeks in Cyr61KD groups. Wnt5aOX resulted in high 
      numbers of vessels and muscle content (~206 vessels/mm2 and ~51%, respectively) 
      at 4 weeks. Over-expressing cell constructs resulted in peripheral nerve 
      regeneration while Cyr61KD animals were devoid of peripheral nerve regeneration 
      at 4 weeks. At 10 weeks post-grafting, peripheral nerve regeneration was at a 
      minimal level for both Cyr61OX and Wnt5aOX cell lines. Blood vessel and bladder 
      functionality were evident at both time-points in all animals. Results from this 
      study indicate that MSC-based Cyr61OX and Wnt5aOX cell lines play pivotal roles 
      with regards to increasing the levels of functional vasculature, influencing 
      muscle regeneration, and the regeneration of peripheral nerves in a model of 
      bladder augmentation. Wnt5aOX constructs closely approximated the outcomes 
      previously observed with the co-transplantation of MSCs with CD34+ HSPCs and may 
      be specifically targeted as an alternate means to achieve functional bladder 
      regeneration.
FAU - Snow-Lisy, Devon C
AU  - Snow-Lisy DC
AD  - Ann & Robert H. Lurie Children's Hospital of Chicago, Division of Pediatric 
      Urology, Chicago, IL, United States of America.
FAU - Diaz, Edward C
AU  - Diaz EC
AD  - Ann & Robert H. Lurie Children's Hospital of Chicago, Division of Pediatric 
      Urology, Chicago, IL, United States of America.
FAU - Bury, Matthew I
AU  - Bury MI
AD  - Ann & Robert H. Lurie Children's Hospital of Chicago, Division of Pediatric 
      Urology, Chicago, IL, United States of America.
FAU - Fuller, Natalie J
AU  - Fuller NJ
AD  - Ann & Robert H. Lurie Children's Hospital of Chicago, Division of Pediatric 
      Urology, Chicago, IL, United States of America.
FAU - Hannick, Jessica H
AU  - Hannick JH
AD  - Department of Urology, Loyola University Health System, Maywood, IL, United 
      States of America.
FAU - Ahmad, Nida
AU  - Ahmad N
AD  - Ann & Robert H. Lurie Children's Hospital of Chicago, Division of Pediatric 
      Urology, Chicago, IL, United States of America.
FAU - Sharma, Arun K
AU  - Sharma AK
AD  - Ann & Robert H. Lurie Children's Hospital of Chicago, Division of Pediatric 
      Urology, Chicago, IL, United States of America; Northwestern University Feinberg 
      School of Medicine, Department of Urology, Chicago, IL, United States of America; 
      Northwestern University, Simpson Querrey Institute for BioNanotechnology, 
      Chicago, IL, United States of America; Northwestern University, Department of 
      Biomedical Engineering, Evanston, IL, United States of America.
LA  - eng
PT  - Journal Article
DEP - 20150923
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antigens, CD34)
RN  - 0 (CCN1 protein, human)
RN  - 0 (Cysteine-Rich Protein 61)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (WNT5A protein, human)
RN  - 0 (Wnt Proteins)
RN  - 0 (Wnt-5a Protein)
SB  - IM
MH  - Animals
MH  - Antigens, CD34/metabolism
MH  - Blood Vessels/metabolism
MH  - Bone Marrow Cells/cytology
MH  - Cell Line
MH  - Cysteine-Rich Protein 61/antagonists & inhibitors/genetics/metabolism
MH  - Disease Models, Animal
MH  - Female
MH  - Humans
MH  - Mesenchymal Stem Cell Transplantation
MH  - Mesenchymal Stem Cells/cytology/metabolism
MH  - Nerve Regeneration
MH  - Proto-Oncogene Proteins/genetics/metabolism
MH  - Rats
MH  - Rats, Nude
MH  - Regeneration/*physiology
MH  - Tissue Engineering
MH  - Urinary Bladder/*physiology
MH  - Urodynamics
MH  - Wnt Proteins/genetics/metabolism
MH  - Wnt-5a Protein
PMC - PMC4580420
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/09/24 06:00
MHDA- 2016/06/15 06:00
PMCR- 2015/09/23
CRDT- 2015/09/24 06:00
PHST- 2015/06/19 00:00 [received]
PHST- 2015/08/03 00:00 [accepted]
PHST- 2015/09/24 06:00 [entrez]
PHST- 2015/09/24 06:00 [pubmed]
PHST- 2016/06/15 06:00 [medline]
PHST- 2015/09/23 00:00 [pmc-release]
AID - PONE-D-15-26982 [pii]
AID - 10.1371/journal.pone.0138643 [doi]
PST - epublish
SO  - PLoS One. 2015 Sep 23;10(9):e0138643. doi: 10.1371/journal.pone.0138643. 
      eCollection 2015.