PMID- 23197855 OWN - NLM STAT- MEDLINE DCOM- 20140227 LR - 20211021 IS - 2157-6564 (Print) IS - 2157-6580 (Electronic) IS - 2157-6564 (Linking) VI - 1 IP - 6 DP - 2012 Jun TI - Perivascular stem cells: a prospectively purified mesenchymal stem cell population for bone tissue engineering. PG - 510-9 LID - 10.5966/sctm.2012-0002 [doi] AB - Adipose tissue is an ideal source of mesenchymal stem cells for bone tissue engineering: it is largely dispensable and readily accessible with minimal morbidity. However, the stromal vascular fraction (SVF) of adipose tissue is a heterogeneous cell population, which leads to unreliable bone formation. In the present study, we prospectively purified human perivascular stem cells (PSCs) from adipose tissue and compared their bone-forming capacity with that of traditionally derived SVF. PSCs are a population (sorted by fluorescence-activated cell sorting) of pericytes (CD146+CD34-CD45-) and adventitial cells (CD146-CD34+CD45-), each of which we have previously reported to have properties of mesenchymal stem cells. Here, we found that PSCs underwent osteogenic differentiation in vitro and formed bone after intramuscular implantation without the need for predifferentiation. We next sought to optimize PSCs for in vivo bone formation, adopting a demineralized bone matrix for osteoinduction and tricalcium phosphate particle formulation for protein release. Patient-matched, purified PSCs formed significantly more bone in comparison with traditionally derived SVF by all parameters. Recombinant bone morphogenetic protein 2 increased in vivo bone formation but with a massive adipogenic response. In contrast, recombinant Nel-like molecule 1 (NELL-1; a novel osteoinductive growth factor) selectively enhanced bone formation. These studies suggest that adipose-derived human PSCs are a new cell source for future efforts in skeletal regenerative medicine. Moreover, PSCs are a stem cell-based therapeutic that is readily approvable by the U.S. Food and Drug Administration, with potentially increased safety, purity, identity, potency, and efficacy. Finally, NELL-1 is a candidate growth factor able to induce human PSC osteogenesis. FAU - James, Aaron W AU - James AW AD - Dental and Craniofacial Research Institute, University of California, Los Angeles, USA. 900950-1579, USA. FAU - Zara, Janette N AU - Zara JN FAU - Zhang, Xinli AU - Zhang X FAU - Askarinam, Asal AU - Askarinam A FAU - Goyal, Raghav AU - Goyal R FAU - Chiang, Michael AU - Chiang M FAU - Yuan, Wei AU - Yuan W FAU - Chang, Le AU - Chang L FAU - Corselli, Mirko AU - Corselli M FAU - Shen, Jia AU - Shen J FAU - Pang, Shen AU - Pang S FAU - Stoker, David AU - Stoker D FAU - Wu, Ben AU - Wu B 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 - T32 DE007296/DE/NIDCR NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120611 PL - England TA - Stem Cells Transl Med JT - Stem cells translational medicine JID - 101578022 RN - 0 (Antigens, CD34) RN - 0 (BMP2 protein, human) RN - 0 (Bone Morphogenetic Protein 2) RN - 0 (CD146 Antigen) RN - 0 (Calcium Phosphates) RN - 0 (Calcium-Binding Proteins) RN - 0 (MCAM protein, human) RN - 0 (NELL1 protein, human) RN - 0 (Nerve Tissue Proteins) RN - 0 (Recombinant Proteins) RN - EC 3.1.3.48 (Leukocyte Common Antigens) RN - EC 3.1.3.48 (PTPRC protein, human) RN - K4C08XP666 (tricalcium phosphate) SB - IM MH - Adipogenesis MH - Adipose Tissue, White/cytology/metabolism MH - Animals MH - Antigens, CD34/metabolism MH - Bone Matrix/metabolism MH - Bone Morphogenetic Protein 2/metabolism/pharmacology MH - *Bone Regeneration MH - CD146 Antigen/metabolism MH - Calcium Phosphates/metabolism MH - Calcium-Binding Proteins MH - Cell Culture Techniques MH - Flow Cytometry MH - Humans MH - Immunohistochemistry MH - Leukocyte Common Antigens/metabolism MH - Lipectomy MH - Male MH - Mesenchymal Stem Cells/*cytology/drug effects/metabolism MH - Mice MH - Mice, SCID MH - Nerve Tissue Proteins/metabolism MH - *Osteogenesis MH - Pericytes/*cytology/drug effects MH - Prospective Studies MH - Recombinant Proteins/metabolism/pharmacology MH - Regenerative Medicine/methods MH - Tissue Scaffolds MH - X-Ray Microtomography PMC - PMC3659717 EDAT- 2012/12/01 06:00 MHDA- 2014/02/28 06:00 PMCR- 2013/06/01 CRDT- 2012/12/01 06:00 PHST- 2012/12/01 06:00 [entrez] PHST- 2012/12/01 06:00 [pubmed] PHST- 2014/02/28 06:00 [medline] PHST- 2013/06/01 00:00 [pmc-release] AID - sctm.2012-0002 [pii] AID - 3781956 [pii] AID - 10.5966/sctm.2012-0002 [doi] PST - ppublish SO - Stem Cells Transl Med. 2012 Jun;1(6):510-9. doi: 10.5966/sctm.2012-0002. Epub 2012 Jun 11.