PMID- 24405888
OWN - NLM
STAT- MEDLINE
DCOM- 20140911
LR  - 20220321
IS  - 1757-6512 (Electronic)
IS  - 1757-6512 (Linking)
VI  - 4
IP  - 5
DP  - 2013 Oct 2
TI  - Human umbilical cord mesenchymal stromal cells exhibit immature nucleus pulposus 
      cell phenotype in a laminin-rich pseudo-three-dimensional culture system.
PG  - 120
LID - 10.1186/scrt331 [doi]
AB  - INTRODUCTION: Cell supplementation to the herniated or degenerated intervertebral 
      disc (IVD) is a potential strategy to promote tissue regeneration and slow disc 
      pathology. Human umbilical cord mesenchymal stromal cells (HUCMSCs) - originating 
      from the Wharton's jelly - remain an attractive candidate for such endeavors with 
      their ability to differentiate into multiple lineages. Previously, mesenchymal 
      stem cells (MSCs) have been studied as a potential source for disc tissue 
      regeneration. However, no studies have demonstrated that MSCs can regenerate 
      matrix with unique characteristics matching that of immature nucleus pulposus 
      (NP) tissues of the IVD. In our prior work, immature NP cells were found to 
      express specific laminin isoforms and laminin-binding receptors that may serve as 
      phenotypic markers for evaluating MSC differentiation to NP-like cells. The goal 
      of this study is to evaluate these markers and matrix synthesis for HUCMSCs 
      cultured in a laminin-rich pseudo-three-dimensional culture system. METHODS: 
      HUCMSCs were seeded on top of Transwell inserts pre-coated with Matrigel, which 
      contained mainly laminin-111. Cells were cultured under hypoxia environment with 
      three differentiation conditions: NP differentiation media (containing 2.5% 
      Matrigel solution to provide for a pseudo-three-dimensional laminin culture 
      system) with no serum, or the same media supplemented with either insulin-like 
      growth factor-1 (IGF-1) or transforming growth factor-beta1 (TGF-beta1). Cell 
      clustering behavior, matrix production and the expression of NP-specific laminin 
      and laminin-receptors were evaluated at days 1, 7, 13 and 21 of culture. RESULTS: 
      Data show that a pseudo-three-dimensional culture condition (laminin-1 rich) 
      promoted HUCMSC differentiation under no serum conditions. Starting at day 1, 
      HUCMSCs demonstrated a cell clustering morphology similar to that of immature NP 
      cells in situ and that observed for primary immature NP cells within the similar 
      laminin-rich culture system (prior study). Differentiated HUCMSCs under all 
      conditions were found to contain glycosaminoglycan, expressed extracellular 
      matrix proteins of collagen II and laminin alpha5, and laminin receptors (integrin alpha3 
      and beta4 subunits). However, neither growth factor treatment generated distinct 
      differences in NP-like phenotype for HUCMSC as compared with no-serum conditions. 
      CONCLUSIONS: HUCMSCs have the potential to differentiate into cells sharing 
      features with immature NP cells in a laminin-rich culture environment and may be 
      useful for IVD cellular therapy.
FAU - Chon, Brian H
AU  - Chon BH
FAU - Lee, Esther J
AU  - Lee EJ
FAU - Jing, Liufang
AU  - Jing L
FAU - Setton, Lori A
AU  - Setton LA
FAU - Chen, Jun
AU  - Chen J
LA  - eng
GR  - R01AR057410/AR/NIAMS NIH HHS/United States
GR  - R01AR047442/AR/NIAMS NIH HHS/United States
GR  - R01 AR057410/AR/NIAMS NIH HHS/United States
GR  - R01 EB002263/EB/NIBIB NIH HHS/United States
GR  - R01EB002263/EB/NIBIB NIH HHS/United States
GR  - R01 AR047442/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20131002
PL  - England
TA  - Stem Cell Res Ther
JT  - Stem cell research & therapy
JID - 101527581
RN  - 0 (Collagen Type II)
RN  - 0 (Glycosaminoglycans)
RN  - 0 (Integrin alpha3)
RN  - 0 (Integrin beta4)
RN  - 0 (Laminin)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (laminin alpha5)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
SB  - IM
CIN - Stem Cell Res Ther. 2013;4(6):142. PMID: 24456755
MH  - Cell Culture Techniques
MH  - Cell Differentiation/drug effects
MH  - Cell Hypoxia
MH  - Cells, Cultured
MH  - Cluster Analysis
MH  - Collagen Type II/metabolism
MH  - Extracellular Matrix/metabolism
MH  - Gene Expression/drug effects
MH  - Glycosaminoglycans/metabolism
MH  - Humans
MH  - Insulin-Like Growth Factor I/pharmacology
MH  - Integrin alpha3/genetics/metabolism
MH  - Integrin beta4/genetics/metabolism
MH  - Intervertebral Disc/cytology/metabolism
MH  - Laminin/genetics/metabolism
MH  - Mesenchymal Stem Cells/*cytology
MH  - Phenotype
MH  - Time Factors
MH  - Transforming Growth Factor beta1/pharmacology
MH  - Umbilical Cord/*cytology
PMC - PMC3854685
EDAT- 2014/01/11 06:00
MHDA- 2014/09/12 06:00
PMCR- 2013/10/02
CRDT- 2014/01/11 06:00
PHST- 2013/03/28 00:00 [received]
PHST- 2013/09/25 00:00 [accepted]
PHST- 2014/01/11 06:00 [entrez]
PHST- 2014/01/11 06:00 [pubmed]
PHST- 2014/09/12 06:00 [medline]
PHST- 2013/10/02 00:00 [pmc-release]
AID - scrt331 [pii]
AID - 10.1186/scrt331 [doi]
PST - epublish
SO  - Stem Cell Res Ther. 2013 Oct 2;4(5):120. doi: 10.1186/scrt331.