Adipose tissue engineering based on human preadipocytes combined with gelatin microspheres containing basic fibroblast growth factor

Kimura, Yu; Ozeki, Makoto; Inamoto, Takashi; Tabata, Yasuhiko

doi:10.1016/s0142-9612(03)00049-8

Cited by 236 publications

(161 citation statements)

References 33 publications

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“…We used gelatin hydrogel microspheres for controlled release of FGF-2 over an extended period of time as in previous studies. 22,23,43 Sequential administration of FGF-2 may be another way to achieve therapeutic effectiveness. The concentration is also important because a high dose of FGF-2 may cause an excessive inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic potential of fibroblast growth factor-2 for hypertrophic scars: upregulation of MMP-1 and HGF expression

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Aoi

et al. 2012

Laboratory Investigation

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Although hypertrophic scars (HTSs) and keloids are challenging problems, their pathogenesis is not well understood, making therapy difficult. We showed that matrix metalloproteinase (MMP)-1 expression was downregulated in HTS compared with normal skin from the same patients, whereas type 1 and 3 collagen and transforming growth factor-b (TGF-b) were upregulated. These differences, however, were not seen in cultured fibroblasts, suggesting the involvement of microenvironmental factors in the pathogenesis of HTS. Fibroblast growth factor-2 (FGF-2) highly upregulated the expression of MMP-1 and hepatocyte growth factor (HGF) in both HTS-derived and control fibroblasts; the upregulation was reversed by extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) inhibitors. An animal study using human HTS tissue implanted into nude mice indicated that controlled-release FGF-2 resulted in significantly less weight and decreased hydroxyproline content in HTS. Degradation of collagen fibers in FGF-2-treated HTS was also confirmed histologically. Western blotting showed that FGF-2-treated HTS expressed significantly higher MMP-1 protein than control. Decreased MMP-1 expression may be an important transcriptional change in HTS, and its reversal as well as upregulation of HGF by FGF-2 could be a new therapeutic approach for HTS.

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Section: Discussionmentioning

confidence: 99%

Therapeutic potential of fibroblast growth factor-2 for hypertrophic scars: upregulation of MMP-1 and HGF expression

Eto

Suga

Aoi

et al. 2012

Laboratory Investigation

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“…In addition, the secretion of vascular endothelial growth factor (a bioactive molecule secreted from the vascular system) around the transplanted graft in recipients is also important for long-term cell survival (Yamaguchi et al, 2005). Particularly, recent studies have highlighted the importance of various cytokines for the regulation of cell function and the surrounding matrix conditions (Kimura et al, 2003;Cho et al, 2006;Torio-Padron et al, 2007b;Kuramochi et al, 2008;Ning et al, 2009). Together with the consideration of cytokine delivery for the transplanted cells, the development of scaffolds for transplantation contributes to the early construction of the surrounding matrix around the transplanted site.…”

Section: Introductionmentioning

confidence: 99%

Fibrin glue increases the cell survival and the transduced gene product secretion of the ceiling culture-derived adipocytes transplanted in mice

et al. 2011

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The development of clinically applicable scaffolds is important for the application of cell transplantation in various human diseases. The aims of this study are to evaluate fibrin glue in a novel protein replacement therapy using proliferative adipocytes and to develop a mouse model system to monitor the delivery of the transgene product into the blood and the fate of the transduced cells after transplantation. Proliferative adipocytes from mouse adipose tissue were transduced by a retroviral vector harboring the human lecithin-cholesterol acyltransferase (lcat) gene, and were subcutaneously transplanted into mice combined with fibrin glue. The lcat gene transduction efficiency and the subsequent secretion of the product in mouse adipocytes were enhanced using a protamine concentration of 500 μ g/ml. Adipogenesis induction did not significantly affect the lcat gene-transduced cell survival after transplantation. Immunohistochemistry showed the ectopic enzyme production to persist for 28 days in the subcutaneously transplanted genetransduced adipocytes. The increased viability of transplanted cells with fibrin glue was accompanied with the decrease in apoptotic cell death. The immunodetectable serum LCAT levels in mice implanted with the fibrin glue were comparable with those observed in mice implanted with Matrigel, indicating that the transplanted lcat gene-transduced adipocytes survived and functioned in the transplanted spaces with fibrin glue as well as with Matrigel for 28 days. Thus, this in vivo system using fibrin is expected to serve as a good model to further improve the transplanted cell/scaffold conditions for the stable and durable cell-based replacement of defective proteins in patients with LCAT deficiency.

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“…duction can enhance preadipocyte implantation-mediated adipose tissue formation. Subcutaneous preadipoHuman Preadipocyte Isolation and Culture cyte implantation using a collagen sponge combined with bFGF-laden gelatin microspheres promoted adipose Human subcutaneous adipose tissues were obtained by elective liposuction from informed and consenting tissue formation (27). Preadipocytes coimplanted with fragmented omentum (an EC source) also enhanced in patients.…”

Section: Introductionmentioning

confidence: 99%

Engineered Adipose Tissue Formation Enhanced by Basic Fibroblast Growth Factor and a Mechanically Stable Environment

et al. 2007

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Engineered adipose tissue can be used in plastic and reconstructive surgery to augment soft tissue lost due to mastectomy or lumpectomy. The three-dimensional space provided by a scaffold capable of withstanding in vivo compressive forces and neovascularization may promote engineered adipose tissue formation. The objective of this study was to determine whether voluminous adipose tissue can be engineered by combining a mechanically stable environment with basic fibroblast growth factor (bFGF). Mechanical support structures, fabricated from biodegradable synthetic polymers, were placed into subcutaneous pockets of athymic mice. Human preadipocytes, containing fibrin matrix, with (group 1) or without (group 2) bFGF were injected into the space created by the support structures. Additionally, human preadipocytes containing fibrin matrix, with (group 3) or without (group 4) bFGF, were injected into subcutaneous spaces without support structures. Six weeks after implantation, the original implant volume was approximately maintained in groups 1 and 2, whereas groups 3 and 4 showed significant implant shrinkage. Adipogenesis and angiogenesis were more extensive in the group 1 than any other group. The fraction of human nuclear antigen-positive adipocytes in the implant was highest in group 1. Mouse adipocyte-specific genes were also expressed in the implants, again at the highest levels in group 1. Implanted preadipocyte apoptosis was significantly reduced in the groups treated with bFGF (groups 1 and 3) as opposed to those without (groups 2 and 4). This study demonstrates that combining a mechanically stable environment with bFGF can promote voluminous adipose tissue regeneration. This adipogenesis was likely promoted by the mechanically stable three-dimensional space, enhanced neovascularization, implanted cell survival, and host adipogenic cell migration. The method described in this study could be useful to augment adipose tissue used in plastic and reconstructive surgery.

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Adipose tissue engineering based on human preadipocytes combined with gelatin microspheres containing basic fibroblast growth factor

Cited by 236 publications

References 33 publications

Therapeutic potential of fibroblast growth factor-2 for hypertrophic scars: upregulation of MMP-1 and HGF expression

Therapeutic potential of fibroblast growth factor-2 for hypertrophic scars: upregulation of MMP-1 and HGF expression

Fibrin glue increases the cell survival and the transduced gene product secretion of the ceiling culture-derived adipocytes transplanted in mice

Engineered Adipose Tissue Formation Enhanced by Basic Fibroblast Growth Factor and a Mechanically Stable Environment

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