Wound healing requires abundant nutrition and blood supply, thus angiogenesis is a vital stage in this process. Angiogenesis involves diverse kinds of immune cells, growth factors, cytokines and inhibitors. ADSCs, esp...Wound healing requires abundant nutrition and blood supply, thus angiogenesis is a vital stage in this process. Angiogenesis involves diverse kinds of immune cells, growth factors, cytokines and inhibitors. ADSCs, especially ADSCs cultured in hypoxic condition, are reported to be able to facilitate angiogenesis and promote wound healing process. Significant efforts have been made on the development of ADSCs-based therapies with wound-healing applications. Here the results showed that expression of Angiopoietin-2 (ANGPT2) in ADSCs was up-regulated in the hypoxic condition.展开更多
Extracellular vesicles(EVs)such as microvesicles(MIVs)play an important role in intercellular communications.MIVs are small membrane vesicles sized 100e1000 nm in diameter that are released by many types of cells,such...Extracellular vesicles(EVs)such as microvesicles(MIVs)play an important role in intercellular communications.MIVs are small membrane vesicles sized 100e1000 nm in diameter that are released by many types of cells,such as mesenchymal stem cells(MSCs),tumor cells and adipose-derived stem cells(ADSC).As EVs can carry out autocrine and paracrine functions by controlling multiple cell processes,it is conceivable that EVs can be used as delivery vehicles for treating several clinical conditions,such as to improve cardiac angiogenesis after myocardial infarction(MI).Here,we seek to investigate whether ADSC-derived MIVs contain microRNAs that regulate angiogenesis and affect cell migration of endothelial cells.We first characterized the ADSC-derived MIVs and found that the MIVs had a size range of 100 e300 nm,and expressed the MIV marker protein Alix.We then analyzed the microRNAs in ADSCs and ADSC-derived MIVs and demonstrated that ADSC-derived MIVs selectively released a panel of microRNAs,several of which were related to angiogenesis,including two members of the let-7 family.Furthermore,we demonstrated that ADSC-derived MIVs promoted the cell migration and invasion of the HUVEC endothelial cells.The PKH26-labeled ADSC-derived MIVs were effectively uptaken into the cytoplasm of HUVEC cells.Collectively,our results demonstrate that the ADSC-derived MIVs can promote migration and invasion abilities of endothelial cells,suggesting pro-angiogenetic potential.Future studies should focus on investigating the roles and mechanisms through which ADSC-derived MIVs regulate angiogenesis.展开更多
Severe burns are challenging to heal and result in significant death throughout the world.Adiposederived mesenchymal stem cells(ADSCs)have emerged as a promising treatment for fullthickness burn healing but are impede...Severe burns are challenging to heal and result in significant death throughout the world.Adiposederived mesenchymal stem cells(ADSCs)have emerged as a promising treatment for fullthickness burn healing but are impeded by their low viability and efficiency after grafting in vivo.Nitric oxide(NO)is beneficial in promoting stem cell bioactivity,but whether it can function effectively in vivo is still largely unknown.In this study,we bioprinted an efficient biological scaffold loaded with ADSCs and NO(3D-ADSCs/NO)to evaluate its biological efficacy in promoting severe burn wound healing.The integral 3D-ADSCs/NO hydrogel scaffolds were constructed via 3D bioprinting.Our results shown that 3D-ADSCs/NO can enhance the migration and angiogenesis of Human Umbilical Vein Endothelial Cells(HUVECs).Burn wound healing experiments in mice revealed that 3D-ADSCs/NO accelerated the wound healing by promoting faster epithelialization and collagen deposition.Notably,immunohistochemistry of CD31 suggested an increase in neovascularization,supported by the upregulation of vascular endothelial growth factor(VEGF)mRNA in ADSCs in the 3D biosystem.These findings indicated that 3D-ADSC/NO hydrogel scaffold can promote severe burn wound healing through increased neovascularization via the VEGF signalling pathway.This scaffold may be considered a promising strategy for healing severe burns.展开更多
The functional recovery of peripheral nerve injury(PNI)is unsatisfactory,whereas diabetes mellitus(DM)and its related complications further attenuate the restoration of diabetic PNI(DPNI).Adipose-derived stem cells(AD...The functional recovery of peripheral nerve injury(PNI)is unsatisfactory,whereas diabetes mellitus(DM)and its related complications further attenuate the restoration of diabetic PNI(DPNI).Adipose-derived stem cells(ADSCs)are promising candidates for treatment of DPNI due to their abundant source,excellent differentiation and paracrine ability.Our results showed that ADSCs remarkably enhanced the proliferation and migration of Schwann cells and endothelial cells,and tube formation.Mechanistically,ADSCs could regulate Nrf2/HO-1,NF-κB and PI3K/AKT/mTOR signaling pathways,showing multiple functions in reducing oxidative stress and inflammation,and regulating cell metabolism,growth,survival,proliferation,angiogenesis,differentiation of Schwann cell and myelin formation.In current study,novel graphene foam(GF)/hydrogel-based scaffold was developed to deliver ADSCs for treatment of DPNI.GF/hydrogel scaffold exhibited excellent mechanical strength,suitable porous network,superior electrical conductivity,and good biocompatibility.In vitro results revealed that GF/hydrogel scaffold could obviously accelerate proliferation of Schwann cells.Moreover,in vivo experiments demonstrated that ADSCs-loaded GF/hydrogel scaffold significantly promoted the recovery of DPNI and inhibited the atrophy of targeted muscles,thus providing a novel and attractive therapeutic approach for DPNI patients.展开更多
文摘Wound healing requires abundant nutrition and blood supply, thus angiogenesis is a vital stage in this process. Angiogenesis involves diverse kinds of immune cells, growth factors, cytokines and inhibitors. ADSCs, especially ADSCs cultured in hypoxic condition, are reported to be able to facilitate angiogenesis and promote wound healing process. Significant efforts have been made on the development of ADSCs-based therapies with wound-healing applications. Here the results showed that expression of Angiopoietin-2 (ANGPT2) in ADSCs was up-regulated in the hypoxic condition.
基金The reported work was supported in part by research grants from the Natural Science Foundation of Jiangxi Province China(#20151BAB215005)the Natural Science Foundation of China(#81660029,81360083)+2 种基金TCH was also supported by the Mabel Green Myers Research Endowment Fund,USA and The University of Chicago Orthopaedics Alumni Fund,USA.Funding sources were not involved in the study designin the collection,analysis and interpretation of data,in the writing of the reportand in the decision to submit the paper for publication.
文摘Extracellular vesicles(EVs)such as microvesicles(MIVs)play an important role in intercellular communications.MIVs are small membrane vesicles sized 100e1000 nm in diameter that are released by many types of cells,such as mesenchymal stem cells(MSCs),tumor cells and adipose-derived stem cells(ADSC).As EVs can carry out autocrine and paracrine functions by controlling multiple cell processes,it is conceivable that EVs can be used as delivery vehicles for treating several clinical conditions,such as to improve cardiac angiogenesis after myocardial infarction(MI).Here,we seek to investigate whether ADSC-derived MIVs contain microRNAs that regulate angiogenesis and affect cell migration of endothelial cells.We first characterized the ADSC-derived MIVs and found that the MIVs had a size range of 100 e300 nm,and expressed the MIV marker protein Alix.We then analyzed the microRNAs in ADSCs and ADSC-derived MIVs and demonstrated that ADSC-derived MIVs selectively released a panel of microRNAs,several of which were related to angiogenesis,including two members of the let-7 family.Furthermore,we demonstrated that ADSC-derived MIVs promoted the cell migration and invasion of the HUVEC endothelial cells.The PKH26-labeled ADSC-derived MIVs were effectively uptaken into the cytoplasm of HUVEC cells.Collectively,our results demonstrate that the ADSC-derived MIVs can promote migration and invasion abilities of endothelial cells,suggesting pro-angiogenetic potential.Future studies should focus on investigating the roles and mechanisms through which ADSC-derived MIVs regulate angiogenesis.
基金This work was supported by the Natural Science Foundation of Guangdong Province,China(No.2017A030313889)This work was partly supported by National Natural Science Foundation of China(No.81772368)the Science and Technology Planning Project of Guangdong Province(No.2017B090912007).
文摘Severe burns are challenging to heal and result in significant death throughout the world.Adiposederived mesenchymal stem cells(ADSCs)have emerged as a promising treatment for fullthickness burn healing but are impeded by their low viability and efficiency after grafting in vivo.Nitric oxide(NO)is beneficial in promoting stem cell bioactivity,but whether it can function effectively in vivo is still largely unknown.In this study,we bioprinted an efficient biological scaffold loaded with ADSCs and NO(3D-ADSCs/NO)to evaluate its biological efficacy in promoting severe burn wound healing.The integral 3D-ADSCs/NO hydrogel scaffolds were constructed via 3D bioprinting.Our results shown that 3D-ADSCs/NO can enhance the migration and angiogenesis of Human Umbilical Vein Endothelial Cells(HUVECs).Burn wound healing experiments in mice revealed that 3D-ADSCs/NO accelerated the wound healing by promoting faster epithelialization and collagen deposition.Notably,immunohistochemistry of CD31 suggested an increase in neovascularization,supported by the upregulation of vascular endothelial growth factor(VEGF)mRNA in ADSCs in the 3D biosystem.These findings indicated that 3D-ADSC/NO hydrogel scaffold can promote severe burn wound healing through increased neovascularization via the VEGF signalling pathway.This scaffold may be considered a promising strategy for healing severe burns.
基金This study is financially supported by the National Natural Science Foundation of China(Nos.81971758,51890892,81971712,81870346,and 81700432)the Natural Science Foundation of Shanghai Science and Technology Committee(No.20ZR1431600)+7 种基金This research is also supported by the National Natural Science Foundation of China(No.11761161004)Z.L.acknowledge supports by the National Natural Science Foundation of China-Research Grants Council Joint Research Scheme(Nos.11761161004 and N_HKUST607/17)the IER foundation(No.HT-JD-CXY-201907)“International science and technology cooperation projects”of Science and Technological Bureau of Guangzhou Huangpu District(No.2019GH06)Guangdong Science and Technology Department(No.2020A0505090003)Research Fund of Guangdong-Hong Kong-Macao Joint Laboratory for Intelligent Micro-Nano Optoelectronic Technology(No.2020B1212030010)Technical assistance from the Materials Characterization and Preparation Facilities of The Hong Kong University Of Science And Technology is greatly appreciatedWe also acknowledge the support of Guangdong Provincial Key Laboratory Program(No.2021B1212040001)from the Department of Science and Technology of Guangdong Province.
文摘The functional recovery of peripheral nerve injury(PNI)is unsatisfactory,whereas diabetes mellitus(DM)and its related complications further attenuate the restoration of diabetic PNI(DPNI).Adipose-derived stem cells(ADSCs)are promising candidates for treatment of DPNI due to their abundant source,excellent differentiation and paracrine ability.Our results showed that ADSCs remarkably enhanced the proliferation and migration of Schwann cells and endothelial cells,and tube formation.Mechanistically,ADSCs could regulate Nrf2/HO-1,NF-κB and PI3K/AKT/mTOR signaling pathways,showing multiple functions in reducing oxidative stress and inflammation,and regulating cell metabolism,growth,survival,proliferation,angiogenesis,differentiation of Schwann cell and myelin formation.In current study,novel graphene foam(GF)/hydrogel-based scaffold was developed to deliver ADSCs for treatment of DPNI.GF/hydrogel scaffold exhibited excellent mechanical strength,suitable porous network,superior electrical conductivity,and good biocompatibility.In vitro results revealed that GF/hydrogel scaffold could obviously accelerate proliferation of Schwann cells.Moreover,in vivo experiments demonstrated that ADSCs-loaded GF/hydrogel scaffold significantly promoted the recovery of DPNI and inhibited the atrophy of targeted muscles,thus providing a novel and attractive therapeutic approach for DPNI patients.
