Open AccessPerivascular Stem Cells: A Prospectively Purified Mesenchymal Stem Cell Population for Bone Tissue Engineering
Author(s) -
James Aaron W.,
Zara Janette N.,
Zhang Xinli,
Askarinam Asal,
Goyal Raghav,
Chiang Michael,
Yuan Wei,
Chang Le,
Corselli Mirko,
Shen Jia,
Pang Shen,
Stoker David,
Wu Ben,
Ting Kang,
Péault Bruno,
Soo Chia
Publication year - 2012
Publication title -
stem cells translational medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.781
H-Index - 71
eISSN - 2157-6580
pISSN - 2157-6564
DOI - 10.5966/sctm.2012-0002
Subject(s) - mesenchymal stem cell , stem cell , microbiology and biotechnology , adipose tissue , stromal vascular fraction , population , bone morphogenetic protein 2 , cd146 , cd34 , stem cell transplantation for articular cartilage repair , tissue engineering , adult stem cell , chemistry , endothelial stem cell , biology , biomedical engineering , medicine , in vitro , biochemistry , environmental health
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.