title: An abundant perivascular source of stem cells for bone tissue engineering.
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.
authors.affiliation: Dental and Craniofacial Research Institute, UCLA, Los Angeles, CA, USA.
authors.forename: Aaron W
authors.initials: AW
authors.lastname: James
authors.forename: Janette N
authors.initials: JN
authors.lastname: Zara
authors.forename: Mirko
authors.initials: M
authors.lastname: Corselli
authors.forename: Asal
authors.initials: A
authors.lastname: Askarinam
authors.forename: Ann M
authors.initials: AM
authors.lastname: Zhou
authors.forename: Alireza
authors.initials: A
authors.lastname: Hourfar
authors.forename: Alan
authors.initials: A
authors.lastname: Nguyen
authors.forename: Silva
authors.initials: S
authors.lastname: Megerdichian
authors.forename: Greg
authors.initials: G
authors.lastname: Asatrian
authors.forename: Shen
authors.initials: S
authors.lastname: Pang
authors.forename: David
authors.initials: D
authors.lastname: Stoker
authors.forename: Xinli
authors.initials: X
authors.lastname: Zhang
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wu
authors.forename: Kang
authors.initials: K
authors.lastname: Ting
authors.forename: Bruno
authors.initials: B
authors.lastname: Péault
authors.forename: Chia
authors.initials: C
authors.lastname: Soo
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D063194:Adventitia; D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D001861:Bone Regeneration; D001842:Bone and Bones; D051929:CD146 Antigen / Q000032:analysis; D002469:Cell Separation; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D020286:Pericytes; D023822:Tissue Engineering; D054457:Tissue Scaffolds; D014945:Wound Healing; D014947:Wounds and Injuries / Q000628:therapy
chemical_list: D018952:Antigens, CD34; D051929:CD146 Antigen; D017493:Leukocyte Common Antigens