An Adipoinductive Role of Inflammation in Adipose Tissue Engineering: Key Factors in the Early Development of Engineered Soft Tissues

Abstract

Tissue engineering and cell implantation therapies are gaining popularity because of their potential to repair and regenerate tissues and organs. To investigate the role of inflammatory cytokines in new tissue development in engineered tissues, we have characterized the nature and timing of cell populations forming new adipose tissue in a mouse tissue engineering chamber (TEC) and characterized the gene and protein expression of cytokines in the newly developing tissues. EGFP-labeled bone marrow transplant mice and MacGreen mice were implanted with TEC for periods ranging from 0.5 days to 6 weeks. Tissues were collected at various time points and assessed for cytokine expression through ELISA and mRNA analysis or labeled for specific cell populations in the TEC. Macrophage-derived factors, such as monocyte chemotactic protein-1 (MCP-1), appear to induce adipogenesis by recruiting macrophages and bone marrow-derived precursor cells to the TEC at early time points, with a second wave of nonbone marrow-derived progenitors. Gene expression analysis suggests that TNFa, LCN-2, and Interleukin 1b are important in early stages of neo-adipogenesis. Increasing platelet-derived growth factor and vascular endothelial cell growth factor expression at early time points correlates with preadipocyte proliferation and induction of angiogenesis. This study provides new information about key elements that are involved in early development of new adipose tissue.

The Angiogenic and Adipogenic Modes of Adipose Tissue after Free Fat Grafting

“…13 Also, Lilja et al found that bone marrow-derived precursor cells infiltrate into adipose tissue under inflammation and become mature adipocytes; this further suggests that most of the regeneration cells that take part in adipogenesis come from recipient circulation. 20 Adipose-derived stromal cells have adipogenic ability, [21][22][23][24] and CD34 + adipose precursor cells may play an important role during adipose tissue regeneration. 25 In the threezone theory reported by Yoshimura et al, they point out that the survival of fat graft was largely determined by adipose tissue regeneration after transplantation and the CD34 + cells were very likely to be the seed cells of the adipogenic progress.…”

Polycaprolactone nanofibrous mesh reduces foreign body reaction and induces adipose flap expansion in tissue engineering chamber

“…Inflammation and angiogenesis are closely interrelated, [55][56][57] and adipose angiogenesis is a key mediator in recruiting adipose precursor cells as well as the subsequent adipogenesis. 58,59 However, there was a reduced inflammatory level and larger final volume of adipose tissue in the PCL group compared with the control group in our study.…”

Generating an Engineered Adipose Tissue Flap Using an External Suspension Device

“…Surgery plays a key role in the angiogenesis and adipogenesis of the tissue-engineering chamber-generated adipose flap by providing necessary trauma/inflammatory conditions. 10,11,15,16 In addition, the flap is subject to changing mechanical forces, leading to the generation of new mitogenic stimuli that promote angiogenesis and adipogenesis. 17 These mechanisms together may explain the growth observed at the early stage in both groups.…”

“…Recent evidence indicates that not only the space provided by the tissue-engineering chamber but also surgical trauma trigger novel tissue formation. 10,11 Therefore, we speculate that providing rigid support from the body surface to create an in vivo space around the pedicled flap would provide similar tissue regeneration and avoid the foreign-body reaction.…”