IGF1 Promotes Adipogenesis by a Lineage Bias of Endogenous Adipose Stem/Progenitor Cells.

Adipogenesis is essential for soft tissue reconstruction following trauma or tumor resection. We demonstrate that CD31(-)/34(+)/146(-) cells, a subpopulation of the stromal vascular fraction (SVF) of human adipose tissue, were robustly adipogenic. Insulin growth factor-1 (IGF1) promoted a lineage bias towards CD31(-)/34(+)/146(-) cells at the expense of CD31(-)/34(+)/146(+) cells. IGF1 was microencapsulated in poly(lactic-co-glycolic acid) scaffolds and implanted in the inguinal fat pad of C57Bl6 mice. Control-released IGF1 induced remarkable adipogenesis in vivo by recruiting endogenous cells. In comparison with the CD31(-)/34(+)/146(+) cells, CD31(-)/34(+)/146(-) cells had a weaker Wnt/ß-catenin signal. IGF1 attenuated Wnt/ß-catenin signaling by activating Axin2/PPARγ pathways in SVF cells, suggesting IGF1 promotes CD31(-)/34(+)/146(-) bias through tuning Wnt signal. PPARγ response element (PPRE) in Axin2 promoter was crucial for Axin2 upregulation, suggesting that PPARγ transcriptionally activates Axin2. Together, these findings illustrate an Axin2/PPARγ axis in adipogenesis that is particularly attributable to a lineage bias towards CD31(-)/34(+)/146(-) cells, with implications in adipose regeneration.

Engineered nasal cartilage by cell homing: a model for augmentative and reconstructive rhinoplasty.

BACKGROUND: Current augmentative and reconstructive rhinoplasties use auto logous tissue grafts or synthetic bioinert materials to repair nasal trauma or attain an aesthetic shape. Autologous grafts are associated with donor-site trauma and morbidity. Synthetic materials are widely used but often yield an unnatural appearance and are prone to infection or dislocation. There is an acute clinical need for the generation of native tissues to serve as rhinoplasty grafts without the undesirable features that are associated with autologous grafts or current synthetic materials. METHODS: Bioactive scaffolds were developed that not only recruited cells in the nasal dorsum in vivo, but also induced chondrogenesis of the recruited cells. Bilayered scaffolds were fabricated with alginate-containing gelatin microspheres encapsulating cytokines atop a porous poly(lactic-co-glycolic acid) base. Microspheres were fabricated to contain recombinant human transforming growth factor-ß3 at doses of 200, 500, or 1000 ng, with phosphate-buffered saline-loaded microspheres used as a control. A rat model of augmentation rhinoplasty was created by implanting scaffolds atop the native nasal cartilage surface that was scored to induce cell migration. Tissue formation and chondrogenesis in the scaffolds were evaluated by image analysis and histologic staining with hematoxylin and eosin, toluidine blue, Verhoeff elastic-van Geison, and aggrecan immunohistochemistry. RESULTS: Sustained release of increasing doses of transforming growth factor-ß3 for up to the tested 10 weeks promoted orthotopic cartilage-like tissue formation in a dose-dependent manner. CONCLUSIONS: These findings represent the first attempt to engineer cartilage tissue by cell homing for rhinoplasty, and could potentially serve as an alternative material for augmentative and reconstructive rhinoplasty.

Adipose tissue engineering from adult human stem cells: a new concept in biosurgery.

Current autologous fat grafting technique suffers from the drawbacks of donor site morbidity and, more importantly, significant resorption of the grafted fat. Adipose tissue engineering using adult human stem cells has been found to overcome the shortcomings of autologous fat grafting in reconstructing facial defects. Mesenchymal stem cells that can self-renew and differentiate into mature adipocytes have been used to generate adipose tissue, in both in vitro and in vivo cell transplantation studies. However, long-term maintenance of the shape and dimension of the produced adipose tissue remains a challenge, even in tissue engineering with cell transplantation. The choice of appropriate scaffolds to promote stem cell adhesion, proliferation, and differentiation is essential for successful adipogenesis. Recent advances in nanotechnology allow the development of nanostructured scaffolds with a cellular environment that maximally enhances not only cell expansion but also the neovascularization that is crucial for long-term maintenance of cell volume. Cell homing is a technique that actively recruits endogenous host stem cells into a predefined anatomic location for the desired tissue generation. Bypassing ex vivo cell manipulation, the cell homing technique eliminates donor site morbidity and rejection, reducing the regulation issue in clinical translation. Mao et al. introduced the concept of biosurgery, which combined nanostructured scaffolds and growth factor biocues, with or without cell transplantation, for successful de novo adipogenesis in restoring facial defects. Important questions, such as the necessity of cell transplantation in scaling up the size of engineered adipose tissue, need to be answered with further studies. However, the era of biosurgery replacing conventional treatments such as biologically inactive filler injections and alloplastic implants appears to be in the near future.

The current trend in augmentation rhinoplasty.

Augmentation rhinoplasty is one of the most commonly performed cosmetic surgeries in Asia. Although they are traditionally considered procedures done predominantly in the Far East, these surgeries have gained increasing popularity in America with the great influx of Asian immigration. This article reviews the unique anatomical features in typical Asian noses, various augmentation options, and the most updated techniques of Asian augmentation rhinoplasty currently being used.