PMID- 23406369
OWN - NLM
STAT- MEDLINE
DCOM- 20131115
LR  - 20231115
IS  - 1937-335X (Electronic)
IS  - 1937-3341 (Print)
IS  - 1937-3341 (Linking)
VI  - 19
IP  - 11-12
DP  - 2013 Jun
TI  - Human perivascular stem cells show enhanced osteogenesis and vasculogenesis with 
      Nel-like molecule I protein.
PG  - 1386-97
LID - 10.1089/ten.TEA.2012.0367 [doi]
AB  - An ideal mesenchymal stem cell (MSC) source for bone tissue engineering has yet 
      to be identified. Such an MSC population would be easily harvested in abundance, 
      with minimal morbidity and with high purity. Our laboratories have identified 
      perivascular stem cells (PSCs) as a candidate cell source. PSCs are readily 
      isolatable through fluorescent-activated cell sorting from adipose tissue and 
      have been previously shown to be indistinguishable from MSCs in the phenotype and 
      differentiation potential. PSCs consist of two distinct cell populations: (1) 
      pericytes (CD146+, CD34-, and CD45-), which surround capillaries and 
      microvessels, and (2) adventitial cells (CD146-, CD34+, and CD45-), found within 
      the tunica adventitia of large arteries and veins. We previously demonstrated the 
      osteogenic potential of pericytes by examining pericytes derived from the human 
      fetal pancreas, and illustrated their in vivo trophic and angiogenic effects. In 
      the present study, we used an intramuscular ectopic bone model to develop the 
      translational potential of our original findings using PSCs (as a combination of 
      pericytes and adventitial cells) from human white adipose tissue. We evaluated 
      human PSC (hPSC)-mediated bone formation and vascularization in vivo. We also 
      examined the effects of hPSCs when combined with the novel 
      craniosynostosis-associated protein, Nel-like molecule I (NELL-1). Implants 
      consisting of the demineralized bone matrix putty combined with NELL-1 (3 mug/muL), 
      hPSC (2.5x10(5) cells), or hPSC+NELL-1, were inserted in the bicep femoris of 
      SCID mice. Bone growth was evaluated using microcomputed tomography, histology, 
      and immunohistochemistry over 4 weeks. Results demonstrated the osteogenic 
      potential of hPSCs and the additive effect of hPSC+NELL-1 on bone formation and 
      vasculogenesis. Comparable osteogenesis was observed with NELL-1 as compared to 
      the more commonly used bone morphogenetic protein-2. Next, hPSCs induced greater 
      implant vascularization than the unsorted stromal vascular fraction from 
      patient-matched samples. Finally, we observed an additive effect on implant 
      vascularization with hPSC+NELL-1 by histomorphometry and immunohistochemistry, 
      accompanied by in vitro elaboration of vasculogenic growth factors. These 
      findings hold significant implications for the cell/protein combination therapy 
      hPSC+NELL-1 in the development of strategies for vascularized bone regeneration.
FAU - Askarinam, Asal
AU  - Askarinam A
AD  - Dental and Craniofacial Research Institute and Section of Orthodontics, School of 
      Dentistry, UCLA, Los Angeles, California, USA.
FAU - James, Aaron W
AU  - James AW
FAU - Zara, Janette N
AU  - Zara JN
FAU - Goyal, Raghav
AU  - Goyal R
FAU - Corselli, Mirko
AU  - Corselli M
FAU - Pan, Angel
AU  - Pan A
FAU - Liang, Pei
AU  - Liang P
FAU - Chang, Le
AU  - Chang L
FAU - Rackohn, Todd
AU  - Rackohn T
FAU - Stoker, David
AU  - Stoker D
FAU - Zhang, Xinli
AU  - Zhang X
FAU - Ting, Kang
AU  - Ting K
FAU - Peault, Bruno
AU  - Peault B
FAU - Soo, Chia
AU  - Soo C
LA  - eng
GR  - G1000816/MRC_/Medical Research Council/United Kingdom
GR  - R21 DE0177711/DE/NIDCR NIH HHS/United States
GR  - R01 DE01607/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130404
PL  - United States
TA  - Tissue Eng Part A
JT  - Tissue engineering. Part A
JID - 101466659
RN  - 0 (Nerve Tissue Proteins)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Blood Vessels/cytology/drug effects/*growth & development
MH  - Cell Differentiation/drug effects
MH  - Cell Proliferation/drug effects
MH  - Cell Separation
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - Implants, Experimental
MH  - Male
MH  - Mice
MH  - Mice, SCID
MH  - *Neovascularization, Physiologic
MH  - Nerve Tissue Proteins/*pharmacology
MH  - *Osteogenesis
MH  - Sheep
MH  - Stem Cells/*cytology
MH  - Stromal Cells/cytology/drug effects
PMC - PMC3638559
EDAT- 2013/02/15 06:00
MHDA- 2013/11/16 06:00
PMCR- 2014/06/01
CRDT- 2013/02/15 06:00
PHST- 2013/02/15 06:00 [entrez]
PHST- 2013/02/15 06:00 [pubmed]
PHST- 2013/11/16 06:00 [medline]
PHST- 2014/06/01 00:00 [pmc-release]
AID - 10.1089/ten.tea.2012.0367 [pii]
AID - 10.1089/ten.TEA.2012.0367 [doi]
PST - ppublish
SO  - Tissue Eng Part A. 2013 Jun;19(11-12):1386-97. doi: 10.1089/ten.TEA.2012.0367. 
      Epub 2013 Apr 4.