Adipose Extracellular Matrix/Stromal Vascular Fraction Gel Secretes Angiogenic Factors and Enhances Skin Wound Healing in a Murine Model

Sun, Mingliang; He, Yunfan; Zhou, Tao; Zhang, Pan; Gao, Jianhua; Lu, Feng

doi:10.1155/2017/3105780

Cited by 54 publications

(39 citation statements)

References 67 publications

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“…The underlying mechanisms of these therapies were attributed to the paracrine growth factors released by various cellular components. Recently, adipose derivatives, such as Nanofat and SVF-gel, containing active SVF components, were shown to exert a therapeutic effect on wounds as reported in multiple basic studies and clinical trials [21,22,24,45]. Nevertheless, ALE therapy is different from these cell-based therapies.…”

Section: Discussionmentioning

confidence: 99%

“…After centrifugation, we found that the processed lipoaspirates were separated into four parts (from top to bottom: lipid portion, lipid-devoid adipose tissue, liquid portion, and cell/tissue debris). The lipid-devoid adipose tissue, namely, extracellular matrix/stromal vascular fraction gel (SVF-gel), was found to have therapeutic ability in inducing angiogenesis and adipogenesis in vivo [20][21][22][23][24]. Unfortunately, the study of the liquid portion acquired from these physically processed lipoaspirates has been ignored.…”

Section: Introductionmentioning

confidence: 99%

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Human adipose liquid extract induces angiogenesis and adipogenesis: a novel cell-free therapeutic agent

Xia

Chen

et al. 2019

Stem Cell Res Ther

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Background Taking advantage of cellular paracrine mechanisms, the secretome of adipose-derived stem cells (ADSCs) and adipose tissue has been demonstrated to induce tissue repair and regeneration in various ischemic and impaired conditions. However, these cell-based therapies have been hindered by issues, such as inherent safety and cost-efficiency for clinical applications. In this study, we prepared a liquid cell-free extract from human adipose tissue [adipose liquid extract (ALE)] and evaluated its potential therapeutic efficacy. Methods ALE was prepared from human subcutaneous adipose tissue using a rapid and physical approach, and the protein components in ALE were identified using mass spectrometry analysis. In vivo, the therapeutic effect of this agent was investigated on wound healing in C57BL/6 mice, and wound healing rate, vessel density, and neo-adipocyte formation in wounded skins were measured at days 3, 7, 11, and 14. In vitro, the effect of ALE on the viability of human ADSCs, tube formation of human umbilical vein endothelial cells (HUVECs), and adipogenic differentiation of ADSCs were tested. Results The results demonstrated that ALE contained a variety of growth factors and did not affect cell viability. ALE-treated wounds exhibited accelerated wound healing with increased vessel density and formation of neo-adipocytes compared to that of control wounds. Moreover, when added as a cell culture supplement, ALE effectively induced tube formation of HUVECs and lipid accumulation in ADSCs. ALE-treated ADSCs also exhibited elevated levels of adipogenic gene expression. Conclusions ALE is a novel growth-rich therapeutic agent that is cell-free and easy to produce. Besides, it is also able to induce angiogenesis and adipogenesis both in vitro and in vivo, thus indicating that it could be used for wound repair and soft tissue regeneration.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Human adipose liquid extract induces angiogenesis and adipogenesis: a novel cell-free therapeutic agent

Xia

Chen

et al. 2019

Stem Cell Res Ther

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“…With the approval of the Ethics Committee of Nanfang Hospital (Guangzhou, China), human lipoaspirate was harvested from female patients undergoing abdominal liposuction after obtaining their informed consent. According to our previous studies, 1 min of mechanical processing of adipose tissue led to the maximum removal of lipid components and minimal ECM fragmentation . Briefly, fresh lipoaspirate was centrifuged at 1,200× g for 3 min.…”

Section: Methodsmentioning

confidence: 99%

“…According to our previous studies, 1 min of mechanical processing of adipose tissue led to the maximum removal of lipid components and minimal ECM fragmentation. 10,11 Briefly, fresh lipoaspirate was centrifuged at 1,2003g for 3 min. The obtained centrifuged fat was mixed with an equal volume of PBS before being mechanically emulsified by repeated transfer between two 10-ml syringes connected by a female-to-female Luer-Lok connector with an internal diameter of 1.4 mm.…”

Section: Preparation Of Ale M-dat and Ordinary Datmentioning

confidence: 99%

Optimized adipose tissue engineering strategy based on a neo‐mechanical processing method

Lin

Wang

et al. 2018

Wound Repair Regeneration

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Decellularized adipose tissue (DAT) represents a promising scaffold for adipose tissue engineering. However, the unique and prolonged lipid removal process required for adipose tissue can damage extracellular matrix (ECM) constituents. Moreover, inadequate vascularization limits the recellularization of DAT in vivo. We proposed a neo-mechanical protocol for rapidly breaking adipocytes and removing lipid content from adipose tissue. The lipid-depleted adipose tissue was then subjected to a fast and mild decellularization to fabricate high-quality DAT (M-DAT). Adipose liquid extract (ALE) derived from this mechanical process was collected and incorporated into M-DAT to further optimize in vivo recellularization. Ordinary DAT was fabricated and served as a control. This developed strategy was evaluated based on decellularization efficiency, ECM quality, and recellularization efficiency. Angiogenic factor components and angiogenic potential of ALE were evaluated in vivo and in vitro. M-DAT achieved the same decellularization efficiency, but exhibited better retention of ECM components and recellularization, compared with those with ordinary DAT. Protein quantification revealed considerable levels of angiogenic factors (basic fibroblast growth factor, epidermal growth factor, transforming growth factor-β1, and vascular endothelial growth factor) in ALE. ALE promoted tube formation in vitro and induced intense angiogenesis in M-DAT in vivo; furthermore, higher expression of the adipogenic factor PPARγ and greater numbers of adipocytes were evident following ALE treatment, compared with those in the M-DAT group. Mechanical processing of adipose tissue led to the production of high-quality M-DAT and angiogenic factor-enriched ALE. The combination of ALE and M-DAT could be a promising strategy for engineered adipose tissue construction.

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“…We recently described an injectable adipose tissue‐derived product, ECM/SVF‐gel, which eliminates adipocytes while preserving the stromal vascular fraction . Furthermore, we identified that ECM/SVF‐gel exhibits greater wound healing effects on wound healing compared with SVF suspension, which is mainly attributed to the high concentration of growth factors secreted by ECM/SVF‐gel . In this regard, we hypothesized that the CM obtained from ECM/SVF‐gel culture may be an attractive source of multiple growth factors for wound repair and regeneration.…”

mentioning

confidence: 99%

Extracellular matrix/stromal vascular fraction gel conditioned medium accelerates wound healing in a murine model

Deng

Feng

et al. 2017

Wound Repair Regeneration

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Conditioned medium (CM) is a new treatment modality in regenerative medicine and has shown a successful outcome in wound healing. We recently introduced extracellular matrix/stromal vascular fraction gel (ECM/SVF-gel), an adipose-derived stem cell and adipose native extracellular matrix-enriched product for cytotherapy. This study aimed to evaluate the effect of CM from ECM/SVF-gel (Gel-CM) on wound healing compared with the conventional CM from adipose tissue (Adi-CM) and stem cell (SVF-CM). In vitro wound healing effect of three CMs on keratinocytes and fibroblasts was evaluated in terms of proliferation property, migratory property, and extracellular matrix production. In vivo, two full-thickness wounds were created on the back of each mice. The wounds were randomly divided to receive Gel-CM, Adi-CM, SVF-CM, and PBS injection. Histologic observations and collagen content of wound skin were made. Growth factors concentration in three CMs was further quantified. In vitro, Gel-CM promoted the proliferation and migration of keratinocytes and fibroblasts and enhanced collagen I synthesis in fibroblasts compared to Adi-CM and SVF-CM. In vivo, wound closure was faster, and dermal and epidermal regeneration was improved in the Gel-CM-treated mice compared to that in Adi-CM and SVF-CM-treated mice. Moreover, The growth factors concentration (i.e., vascular endothelial growth factor, basic fibroblast growth factor, hepatocyte growth factor, and transforming growth factor-β) in Gel-CM were significantly higher than those in Adi-CM and SVF-CM. Gel-CM generated under serum free conditions significantly enhanced wound healing effect compared to Adi-CM and SVF-CM by accelerating cell proliferation, migration, and production of ECM. This improved trophic effect may be attributed to the higher growth factors concentration in Gel-CM. Gel-CM shows potential as a novel and promising alternative to skin wound healing treatment. But limitations include the safety and immunogenicity studies of Gel-CM still remain to be clearly clarified and more data on mechanism study are needed.

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Adipose Extracellular Matrix/Stromal Vascular Fraction Gel Secretes Angiogenic Factors and Enhances Skin Wound Healing in a Murine Model

Cited by 54 publications

References 67 publications

Human adipose liquid extract induces angiogenesis and adipogenesis: a novel cell-free therapeutic agent

Human adipose liquid extract induces angiogenesis and adipogenesis: a novel cell-free therapeutic agent

Optimized adipose tissue engineering strategy based on a neo‐mechanical processing method

Extracellular matrix/stromal vascular fraction gel conditioned medium accelerates wound healing in a murine model

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