Document Detail

Human perivascular stem cells show enhanced osteogenesis and vasculogenesis with Nel-like molecule I protein.
MedLine Citation:
PMID:  23406369     Owner:  NLM     Status:  MEDLINE    
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 μg/μL), hPSC (2.5×10(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.
Asal Askarinam; Aaron W James; Janette N Zara; Raghav Goyal; Mirko Corselli; Angel Pan; Pei Liang; Le Chang; Todd Rackohn; David Stoker; Xinli Zhang; Kang Ting; Bruno Péault; Chia Soo
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-04-04
Journal Detail:
Title:  Tissue engineering. Part A     Volume:  19     ISSN:  1937-335X     ISO Abbreviation:  Tissue Eng Part A     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-04-29     Completed Date:  2013-11-15     Revised Date:  2014-06-03    
Medline Journal Info:
Nlm Unique ID:  101466659     Medline TA:  Tissue Eng Part A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1386-97     Citation Subset:  IM    
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MeSH Terms
Blood Vessels / cytology,  drug effects,  growth & development*
Cell Differentiation / drug effects
Cell Proliferation / drug effects
Cell Separation
Implants, Experimental
Mice, SCID
Neovascularization, Physiologic*
Nerve Tissue Proteins / pharmacology*
Stem Cells / cytology*
Stromal Cells / cytology,  drug effects
Grant Support
G1000816//Medical Research Council; R01 DE01607/DE/NIDCR NIH HHS; R21 DE0177711/DE/NIDCR NIH HHS
Reg. No./Substance:
0/Nerve Tissue Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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