Perivascular stem cells: A prospectively purified mesenchymal stem cell population for bone tissue engineering

Aaron W. James, Janette N. Zara, Xinli Zhang, Asal Askarinam, Raghav Goyal, Michael Chiang, Wei Yuan, Le Chang, Mirko Corselli, Jia Shen, Shen Pang, David Stoker, Ben Wu, Kang Ting, Bruno Péault, Chia Soo

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)510-519
Number of pages10
JournalStem Cells Translational Medicine
Volume1
Issue number6
DOIs
StatePublished - 2012
Externally publishedYes

Keywords

  • Adult stem cells
  • Mesenchymal stem cells
  • Osteoblast
  • Pericytes

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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