Review Article

Comprehensive Review of Adipose Stem Cells and Their Implication in Distraction Osteogenesis and Bone Regeneration

Table 3

Overview of the studies performed on bone regeneration and distraction osteogenesis using ASC.

AuthorCell typeScaffoldModelObservation

ASC’s application with scaffolds, without the use of growth factors

Yoon et al. [200]ASC &
d-ASC
PLGACalvarial CSD in ratsd-ASCs with PGLA have better bone regeneration capability in CSD than constructs with ASC alone

Cui et al. [201]ASCCoralCalvarial CSD in dogsBone was almost completely restored in the CSD, when ASCs were applied. Minimal bone formation with fibroid tissues was observed in the control group

Carvalho et al. [202]ASCSPCLCalvarial CSD in miceNondifferentiated human ASCs enhance ossification of nonhealing mice CSD

Schubert et al. [203]d- ASC3D osteogenic ASC(1) Four-level spinal fusion in pigs
(2) Femur CSD in pigs
In a spine fusion model, applying 3D d-ASC demonstrated a significant increase in bone formation
In the femoral CSD model, the 3D d-ASC achieved new bone formation and fusion in a poorly vascularized fibrotic environment

Liu et al. [204]Al- ASCs,
Au-ASC
CoralCranial CSD in dogsAllo-ASC transplantation did not induce a systemic immune response and was able to repair the cranial CSDs in an analogous way to that of the autologous cells

Cowan et al. [205]ASCPGLACalvarial CSD in miceASC showed a significant intramembranous bone formation by 2 weeks and complete bridging by 12 weeks without any additives

Di Bella et al. [206]ASC,
d-ASC
PLA
& FPLA
Skull CSD in rabbits(1) FPLA as a fibronectin-coated scaffold promotes bone formation more than using PLA alone
(2) d-ASCs combined with FPLA enhance bone formation significantly when compared with ASC alone

Lendeckel et al. [207]ASCFibrin glue & bone graftCranial CSD in a 7-year-old girlComplete calvarial healing after 3 months

Nomura et al. [208]ASCCollagen gelDO femur in ratsASC promoted bone formation in the distracted callus and shortening the consolidation phase

Sunay et al. [209]ASC,
d-ASC
DO tibia in rabbitsd-ASC showed increase in the callus density and the ossification rate compared to the undifferentiated ASC. The quality of bone formed within the callus was significantly enhanced. Use of d-ASC can shorten the consolidation period of distraction osteogenesis

Arrigoni et al. [210]ASCHATibia CSD in rabbitsASCs-HA constructs improved bone healing significantly, when compared to using scaffold alone

Cheng et al.
[211]
ASCDBMCalvarial CSD in rabbitsNew bone formation was documented in bone defects transplanted with DBM-ASCs composites

ASC’s application with scaffolds, with the use of growth factors like BMP2 and TGF (β3)

Lin et al. [212]BMP2 expressing ASC and TGF (β3)PLGA or gelatin spongeCalvarial CSD in rabbitsGelatin sponges and apatite coated PLGA were compared as scaffolds. Gelatin scaffold stimulated the bone healing more than apatite coated PLGA, regardless of BMP2 or TGF-β3 expression. The ASCs/gelatin expressing BMP2 triggered better bone healing than ASCs/gelatin expressing TGF-β3

Peterson et al. [213]HPLA, with BMP-2 carrying adenovirusCCCFemur CSD in ratsHPLA cells genetically modified by adenoviruses, overexpressing BMP-2, can induce bone formation in vivo and heal CSD in rat femurs

Levi et al. [214]Human ASC,
with BMP-2
PGLACalvarial CSD in mice(1) Human ASCs ossify CSD without the need for predifferentiation
(2) rBMP-2 was observed to increase human ASC osteogenesis in vitro and osseous healing in vivo

GF:growth factor, PLGA: polylactide-co-glycolic acid, d-ASC: differentiated ASC, PLA: polylactic acid, SPCL: wet-spun starch polycaprolactone, Allo-ASC: allogeneic ASC, Au-ASC: autologous ASC, FPLA: fibronectin-treated PLA, HPLA: human processed lipoaspirate, CCC: collagen-ceramic carrier, HA: hydroxyapatite, and DBM: demineralized bone matrix.