PMID- 27992567
OWN - NLM
STAT- MEDLINE
DCOM- 20170710
LR  - 20181202
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 11
IP  - 12
DP  - 2016
TI  - Impact of Hyperglycemia and Low Oxygen Tension on Adipose-Derived Stem Cells 
      Compared with Dermal Fibroblasts and Keratinocytes: Importance for Wound Healing 
      in Type 2 Diabetes.
PG  - e0168058
LID - 10.1371/journal.pone.0168058 [doi]
LID - e0168058
AB  - AIM: Adipose-derived stem cells (ASC) are currently proposed for wound healing in 
      those with type 2 diabetes mellitus (T2DM). Therefore, this study investigated 
      the impact of diabetes on adipose tissue in relation to ASC isolation, 
      proliferation, and growth factor release and the impact of hyperglycemia and low 
      oxygen tension (found in diabetic wounds) on dermal fibroblasts, keratinocytes, 
      and ASC in vitro. METHODS: Different sequences of hypoxia and hyperglycemia were 
      applied in vitro to ASC from nondiabetic (n = 8) or T2DM patients (n = 4) to 
      study cell survival, proliferation, and growth factor release. Comparisons of 
      dermal fibroblasts (n = 8) and keratinocytes (primary lineage) were made. 
      RESULTS: No significant difference of isolation and proliferation capacities was 
      found in ASC from nondiabetic and diabetic humans. Hypoxia and hyperglycemia did 
      not impact cell viability and proliferation. Keratinocyte Growth Factor release 
      was significantly lower in diabetic ASC than in nondiabetic ASC group in each 
      condition, while Vascular Endothelial Growth Factor release was not affected by 
      the diabetic origin. Nondiabetic ASC exposition to hypoxia (0.1% oxygen) combined 
      with hyperglycemia (25mM glucose), resulted in a significant increase in VEGF 
      secretion (+64%, p<0.05) with no deleterious impact on KGF release in comparison 
      to physiological conditions (5% oxygen and 5 mM glucose). Stromal cell-Derived 
      Factor-1alpha (-93%, p<0.001) and KGF (-20%, p<0.05) secretion by DF decreased in 
      these conditions. CONCLUSIONS: A better profile of growth factor secretion 
      (regarding wound healing) was found in vitro for ASC in hyperglycemia coupled 
      with hypoxia in comparison to dermal fibroblasts and keratinocytes. 
      Interestingly, ASC from T2DM donors demonstrated cellular growth rates and 
      survival (in hypoxia and hyperglycemic conditions) similar to those of healthy 
      ASC (from normoglycemic donors); however, KGF secretion was significantly 
      depleted in ASC obtained from T2DM patients. This study demonstrated the impact 
      of diabetes on ASC for regenerative medicine and wound healing.
FAU - Lafosse, Aurore
AU  - Lafosse A
AD  - Universite Catholique de Louvain, Brussels, Belgium.
FAU - Dufeys, Cecile
AU  - Dufeys C
AD  - Pole de Recherche Cardiovasculaire (CARD), Institut de Recherche Experimentale et 
      Clinique, Universite Catholique de Louvain, Brussels, Belgium.
FAU - Beauloye, Christophe
AU  - Beauloye C
AD  - Pole de Recherche Cardiovasculaire (CARD), Institut de Recherche Experimentale et 
      Clinique, Universite Catholique de Louvain, Brussels, Belgium.
FAU - Horman, Sandrine
AU  - Horman S
AD  - Pole de Recherche Cardiovasculaire (CARD), Institut de Recherche Experimentale et 
      Clinique, Universite Catholique de Louvain, Brussels, Belgium.
FAU - Dufrane, Denis
AU  - Dufrane D
AD  - Novadip Biosciences, Mont-Saint-Guibert, Belgium.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20161219
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Adipose Tissue/*cytology/metabolism
MH  - Adult
MH  - Aged
MH  - Cell Hypoxia
MH  - Cell Proliferation
MH  - Cell Survival
MH  - Cells, Cultured
MH  - Diabetes Mellitus, Type 2/complications/metabolism/*pathology
MH  - Female
MH  - Fibroblasts/*cytology/metabolism
MH  - Glucose/*pharmacology
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/metabolism
MH  - Keratinocytes/*cytology/metabolism
MH  - Male
MH  - Middle Aged
MH  - Stem Cells/*cytology/metabolism
MH  - Wound Healing
MH  - Young Adult
PMC - PMC5167273
COIS- The authors have no financial interest to declare in relation to the content of 
      this article. Denis Dufrane is the cofounder of Novadip Biosciences and receives 
      a salary for the position of Chief Scientific Officer at Novadip Bioscience. This 
      does not alter our adherence to PLOS ONE policies on sharing data and materials. 
      There are no commercially relevant declarations (relating to employment, 
      consultancy, patents, products in development, or marketed products, etc.) in 
      relation this study.
EDAT- 2016/12/20 06:00
MHDA- 2017/07/14 06:00
PMCR- 2016/12/19
CRDT- 2016/12/20 06:00
PHST- 2016/09/05 00:00 [received]
PHST- 2016/11/25 00:00 [accepted]
PHST- 2016/12/20 06:00 [entrez]
PHST- 2016/12/20 06:00 [pubmed]
PHST- 2017/07/14 06:00 [medline]
PHST- 2016/12/19 00:00 [pmc-release]
AID - PONE-D-16-35663 [pii]
AID - 10.1371/journal.pone.0168058 [doi]
PST - epublish
SO  - PLoS One. 2016 Dec 19;11(12):e0168058. doi: 10.1371/journal.pone.0168058. 
      eCollection 2016.