An abundant perivascular source of stem cells for bone tissue engineering

Aaron W James, Janette N Zara, Mirko Corselli, Asal Askarinam, Ann M Zhou, Alireza Hourfar, Alan Nguyen, Silva Megerdichian, Greg Asatrian, Shen Pang, David Stoker, Xinli Zhang, Benjamin Wu, Kang Ting, Bruno Péault, Chia Soo

Research output: Contribution to journalArticlepeer-review

Abstract

Adipose tissue is an ideal mesenchymal stem cell (MSC) source, as it is dispensable and accessible with minimal morbidity. However, the stromal vascular fraction (SVF) of adipose tissue is a heterogeneous cell population, which has disadvantages for tissue regeneration. In the present study, we prospectively purified human perivascular stem cells (PSCs) from n = 60 samples of human lipoaspirate and documented their frequency, viability, and variation with patient demographics. PSCs are a fluorescence-activated cell sorting-sorted population composed of pericytes (CD45-, CD146+, CD34-) and adventitial cells (CD45-, CD146-, CD34+), each of which we have previously reported to have properties of MSCs. Here, we found that PSCs make up, on average, 43.2% of SVF from human lipoaspirate (19.5% pericytes and 23.8% adventitial cells). These numbers were minimally changed by age, gender, or body mass index of the patient or by length of refrigerated storage time between liposuction and processing. In a previous publication, we observed that human PSCs (hPSCs) formed significantly more bone in vivo in comparison with unsorted human SVF (hSVF) in an intramuscular implantation model. We now extend this finding to a bone injury model, observing that purified hPSCs led to significantly greater healing of mouse critical-size calvarial defects than hSVF (60.9% healing as opposed to 15.4% healing at 2 weeks postoperative by microcomputed tomography analysis). These studies suggest that adipose-derived hPSCs are a new cell source for future efforts in skeletal regenerative medicine. Moreover, hPSCs 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.
Original languageEnglish
Pages (from-to)673-684
Number of pages12
JournalStem Cells Translational Medicine
Volume1
Issue number9
DOIs
Publication statusPublished - Sep 2012

Keywords

  • Animals
  • Tissue Engineering
  • Bone and Bones
  • Wound Healing
  • Humans
  • Wounds and Injuries
  • Tissue Scaffolds
  • Mice
  • Cell Separation
  • Adipose Tissue
  • Antigens, CD146
  • Antigens, CD34
  • Bone Regeneration
  • Antigens, CD45
  • Mesenchymal Stromal Cells
  • Pericytes
  • Adventitia

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