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

Abstract

Bone is one of the most dynamic tissues in the human body that can heal following injury without leaving a scar. However, in instances of extensive bone loss, this intrinsic capacity of bone to heal may not be sufficient and external intervention becomes necessary. Several techniques are available to address this problem, including autogenous bone grafts and allografts. However, all these techniques have their own limitations. An alternative method is the technique of distraction osteogenesis, where gradual and controlled distraction of two bony segments after osteotomy leads to induction of new bone formation. Although distraction osteogenesis usually gives satisfactory results, its major limitation is the prolonged duration of time required before the external fixator is removed, which may lead to numerous complications. Numerous methods to accelerate bone formation in the context of distraction osteogenesis have been reported. A viable alternative to autogenous bone grafts for a source of osteogenic cells is mesenchymal stem cells from bone marrow. However, there are certain problems with bone marrow aspirate. Hence, scientists have investigated other sources for mesenchymal stem cells, specifically adipose tissue, which has been shown to be an excellent source of mesenchymal stem cells. In this paper, the potential use of adipose stem cells to stimulate bone formation is discussed.

Figure 1

Schematic representation of distraction osteogenesis technique. (a) The tibial bone that needs lengthening. (b) Application of circular external fixator. (c) Tibial and fibular osteotomy. (d) Distraction phase and new bone formation. (e) Consolidation phase.

Figure 2

Lengthening of short tibia showing various phases of the distraction process. (a) Application of the fixator and osteotomy of the tibia. (b) Start of distraction. (c) End of distraction. (d and e) Consolidation phase, without any distraction until bone in the distracted gap consolidates. (f) Removal of the fixator (bar scale = 5 cm).

Figure 3

Histological changes using trichrome staining, in a rabbit DO model during distraction osteogenesis of the tibia. (a) to (c) represent the cellular change that happen during the distraction phase while (d) to (f) represent the cellular change that happen during the consolidation phase. Co: cortex; LZ: lengthened zone; Ca: callus; FIZ: fibrous interzone (bar scale = 2 mm).

Figure 4

Schematic representation of BMP's effect on the differentiation of adipose stem cells into osteoblast.

Figure 5

Schematic representation of stem cell isolation sites. This schematic shows that adult stem cells can be found in both bone marrow and adipose tissue. Both BM-MSC and ASC are capable of differentiating into the same three lineages' osteoblast, chondrocyte, and adipocyte.

Figure 6

Schematic representation of different stimulating factors that can affect the differentiation of adipose stem cells into osteoblast.

Figure 7

Representation of callus classification. Illustration and radiographs demonstrate the modified Li classification of callus shape in distraction osteogenesis. (a) New bone formation in the distraction gap extends beyond the outer borders of the cortical bone. (b) New bone formation toward one side of the distraction gap with extension beyond the outer borders of the adjacent cortical bone. (c) New bone formation within the distraction gap with margins parallel to the adjacent cortical bone. (d) Biconcave-shaped new bone formation within the distraction gap. (e) New bone formation limited to one side of the bone without extension beyond the outer borders of the cortical bone. (f) New bone formation in the center with limited new bone regeneration in the lateral portion of the distraction gap. (g) Only speckled bone formation is present (bar scale = 5 cm).