title: Enhancement of bone regeneration using osteogenic-induced adipose-derived stem cells combined with demineralized bone matrix in a rat critically-sized calvarial defect model.
abstract: BACKGROUND
  Human adipose tissue contains pluripotent stem cells that are similar to bone marrow-derived stem cells. The present study examined whether osteogenic induced adipose-derived stem cells (ASCs) could enhance the osteogenic capacity of demineralized bone matrix and accelerate bone formation in a rat critically-sized calvarial defect model.
  
  
  METHODS
  Forty Sprague-Dawley rats were divided randomly into four groups containing 10 rats per each group (Control, 0.05 cc fibrin glue (25 mg/ml) and 0.05 cc thrombin (130 U/ml); DBX, control + 0.2 g DBX�; ASC, DBX + 1 x 105 ASCs/g; iASC, DBX + 1 x 105 osteogenic-induced ASCs/g). After osteogenic differentiation of ASCs, alkaline phosphatase and von Kossa staining were performed each week to determine the extent of differentiation and mineralization. An 8-mm critical size circular defect was made in the calvarial bone of each rat. The specimens were harvested 8 weeks after implantation, and radiographic and histological evaluations were carried out. New bone formation was quantified by radiodensitometric analysis of the calvarial sections. Statistical analysis was accomplished using a Mann-Whitney test and Kruskal-Wallis test at a significance level of P < 0.05.
  
  
  RESULTS
  Alkaline phosphatase and von Kossa staining showed that the osteogenic-induced ASCs yielded higher osteogenic differentiation at 3 weeks. The calvarial defect was filled more in the iASC group compared to the other groups, as demonstrated by the gross appearance of the specimen and radiologic evaluation. The mean radiodensity of the control, DBX, ASC, and iASC group was 16.78%, 39.94%, 25.58%, and 51.31%, respectively, and these were significantly different (P=0.034). Histomorphological evaluation confirmed that new bone formation was accelerated and enhanced by the osteogenic-induced ASCs.
  
  
  CONCLUSIONS
  ASCs produced greater osteogenic differentiation at 3 weeks. Osteogenic regeneration was accelerated and enhanced in vivo with the osteogenic-induced ASCs, compared to undifferentiated ASCs. Osteogenic-induced ASCs are an excellent and promising candidate for regenerative medicine and tissue engineering application.
authors.affiliation: BOB Aesthetic Surgery Clinic, Seoul, Republic of Korea.
authors.forename: Hyun Peel
authors.initials: HP
authors.lastname: Kim
authors.forename: Yi-Hwa
authors.initials: YH
authors.lastname: Ji
authors.forename: Seung Chul
authors.initials: SC
authors.lastname: Rhee
authors.forename: Eun Sang
authors.initials: ES
authors.lastname: Dhong
authors.forename: Seung Ha
authors.initials: SH
authors.lastname: Park
authors.forename: Eul-Sik
authors.initials: ES
authors.lastname: Yoon
mesh_terms: D015502:Absorptiometry, Photon; D000273:Adipose Tissue / Q000166:cytology*; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001857:Bone Matrix / Q000737:chemistry; D001861:Bone Regeneration; D002113:Calcification, Physiologic; D002454:Cell Differentiation; D002478:Cells, Cultured; D015718:Fibrin Tissue Adhesive; D006801:Humans; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000637:transplantation*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012886:Skull / Q000187:drug effects* / Q000293:injuries / Q000503:physiopathology; D013917:Thrombin / Q000008:administration & dosage
chemical_list: D015718:Fibrin Tissue Adhesive; D000469:Alkaline Phosphatase; D013917:Thrombin