PDF(Pubmed)
Abstract：
Thermal traumas impose a huge burden on healthcare systems. This merits the need for advanced but cost-effective remedies with clinical prospects. In this context, we prepared a regenerative 3D-construct comprising of Cassia angustifolia extract (SM) primed adipose-derived stem cells (ASCs) laden amniotic membrane for faster burn wound repair.
ASCs were preconditioned with SM (30 µg/ml for 24 h), and subsequently exposed to in-vitro thermal injury (51 °C,10 min). In-vivo thermal injury was induced by placing pre-heated copper-disc (2 cm diameter) on dorsum of the Wistar rats. ASCs (2.0 × 105) pre-treated with SM (SM-ASCs), cultured on stromal side of amniotic membrane (AM) were transplanted in rat heat-injury model. Non-transplanted heat-injured rats and non-heat-injured rats were kept as controls.
The significantly upregulated expression of IGF1, SDF1A, TGFβ1, VEGF, GSS, GSR, IL4, BCL2 genes and downregulation of BAX, IL6, TNFα, and NFkB1 in SM-ASCs in in-vitro and in-vivo settings confirmed its potential in promoting cell-proliferation, migration, angiogenesis, antioxidant, cell-survival, anti-inflammatory, and wound healing activity. Moreover, SM-ASCs induced early wound closure, better architecture, normal epidermal thickness, orderly-arranged collagen fibers, and well-developed skin appendages in healed rat-skin transplanted with AM+SM-ASCs, additionally confirmed by increased expression of structural genes (Krt1, Krt8, Krt19, Desmin, Vimentin, α-Sma) in comparison to untreated-ASCs laden-AM transplanted in heat injured rats.
SM priming effectively enabled ASCs to counter thermal injury by significantly enhancing cell survival and reducing inflammation upon transplantation. This study provides bases for development of effective combinational therapies (natural scaffold, medicine, and stem cells) with clinical prospects for treating burn wounds.
ASCs were preconditioned with SM (30 µg/ml for 24 h), and subsequently exposed to in-vitro thermal injury (51 °C,10 min). In-vivo thermal injury was induced by placing pre-heated copper-disc (2 cm diameter) on dorsum of the Wistar rats. ASCs (2.0 × 105) pre-treated with SM (SM-ASCs), cultured on stromal side of amniotic membrane (AM) were transplanted in rat heat-injury model. Non-transplanted heat-injured rats and non-heat-injured rats were kept as controls.
The significantly upregulated expression of IGF1, SDF1A, TGFβ1, VEGF, GSS, GSR, IL4, BCL2 genes and downregulation of BAX, IL6, TNFα, and NFkB1 in SM-ASCs in in-vitro and in-vivo settings confirmed its potential in promoting cell-proliferation, migration, angiogenesis, antioxidant, cell-survival, anti-inflammatory, and wound healing activity. Moreover, SM-ASCs induced early wound closure, better architecture, normal epidermal thickness, orderly-arranged collagen fibers, and well-developed skin appendages in healed rat-skin transplanted with AM+SM-ASCs, additionally confirmed by increased expression of structural genes (Krt1, Krt8, Krt19, Desmin, Vimentin, α-Sma) in comparison to untreated-ASCs laden-AM transplanted in heat injured rats.
SM priming effectively enabled ASCs to counter thermal injury by significantly enhancing cell survival and reducing inflammation upon transplantation. This study provides bases for development of effective combinational therapies (natural scaffold, medicine, and stem cells) with clinical prospects for treating burn wounds.
摘要：
背景：热创伤给医疗保健系统带来了巨大的负担。这值得需要具有临床前景的先进但具有成本效益的补救措施。在这种情况下，我们制备了一种再生的3D构建体，该构建体包含决明提取物（SM）引发的脂肪干细胞（ASCs）负载羊膜，用于更快的烧伤伤口修复。
方法：用SM（30µg/ml，24小时）预处理ASCs，并随后暴露于体外热损伤(51°C，10分钟)。通过在Wistar大鼠的背部放置预热的铜盘（直径2cm）来诱导体内热损伤。用SM预处理的ASCs（2.0×105）（SM-ASCs），在大鼠热损伤模型中，在羊膜（AM）的基质侧培养。将非移植热损伤大鼠和非热损伤大鼠作为对照。
结果：IGF1、SDF1A、TGFβ1,VEGF,GSS,GSR,IL4，BCL2基因与BAX的下调，IL6,TNFα,和NFkB1在SM-ASC在体外和体内设置证实了其促进细胞增殖的潜力，迁移,血管生成,抗氧化剂，细胞存活，抗炎,和伤口愈合活动。此外，SM-ASCs诱导早期伤口闭合，更好的建筑，正常表皮厚度，有序排列的胶原纤维，移植了AM+SM-ASC的愈合大鼠皮肤和发育良好的皮肤附件，结构基因表达增加(Krt1，Krt8，Krt19，Desmin，Vimentin,α-Sma）与在热损伤大鼠中移植的未处理的ASC负载AM相比。
结论：SM引发通过显著增强细胞存活和减少移植后的炎症，有效地使ASCs对抗热损伤。本研究为开发有效的组合疗法(天然支架，医学,和干细胞）具有治疗烧伤伤口的临床前景。
方法：用SM（30µg/ml，24小时）预处理ASCs，并随后暴露于体外热损伤(51°C，10分钟)。通过在Wistar大鼠的背部放置预热的铜盘（直径2cm）来诱导体内热损伤。用SM预处理的ASCs（2.0×105）（SM-ASCs），在大鼠热损伤模型中，在羊膜（AM）的基质侧培养。将非移植热损伤大鼠和非热损伤大鼠作为对照。
结果：IGF1、SDF1A、TGFβ1,VEGF,GSS,GSR,IL4，BCL2基因与BAX的下调，IL6,TNFα,和NFkB1在SM-ASC在体外和体内设置证实了其促进细胞增殖的潜力，迁移,血管生成,抗氧化剂，细胞存活，抗炎,和伤口愈合活动。此外，SM-ASCs诱导早期伤口闭合，更好的建筑，正常表皮厚度，有序排列的胶原纤维，移植了AM+SM-ASC的愈合大鼠皮肤和发育良好的皮肤附件，结构基因表达增加(Krt1，Krt8，Krt19，Desmin，Vimentin,α-Sma）与在热损伤大鼠中移植的未处理的ASC负载AM相比。
结论：SM引发通过显著增强细胞存活和减少移植后的炎症，有效地使ASCs对抗热损伤。本研究为开发有效的组合疗法(天然支架，医学,和干细胞）具有治疗烧伤伤口的临床前景。
