Neural stem cells(NSCs)are the source of all neurons and glial cells(astrocytes and oligodendrocytes)in the central nervous system.The adult mammalian brain retains NSCs in the subgranular zone of the dentate gyrus in...Neural stem cells(NSCs)are the source of all neurons and glial cells(astrocytes and oligodendrocytes)in the central nervous system.The adult mammalian brain retains NSCs in the subgranular zone of the dentate gyrus in the hippocampus and ventricular subventricular zone lining the lateral ventricle(Olpe and Jessberger,2022).Adult NSCs in rodents are preserved throughout life and continuously produce new neurons that integrate into the pre-existing neuronal network.展开更多
Extracellular vesicles(EVs)provide a novel mechanism of intercellular communication via the transfer of proteins,lipids,and miR NAs between cells.It is now widely accepted that cargo content of EVs depends on cell typ...Extracellular vesicles(EVs)provide a novel mechanism of intercellular communication via the transfer of proteins,lipids,and miR NAs between cells.It is now widely accepted that cargo content of EVs depends on cell type and its physiological state.Accordingly,EVs derived from healthy cells may have a comparable therapeutic potential as cells themselves.Indeed,several studies confirmed this notion展开更多
Alzheimer’s disease(AD)is a major age-related form of dementia with a number of cases exponentially growing,causing enormous social and economic impact on individuals and society.Neuropathological hallmarks of AD,evi...Alzheimer’s disease(AD)is a major age-related form of dementia with a number of cases exponentially growing,causing enormous social and economic impact on individuals and society.Neuropathological hallmarks of AD,evident in postmortem AD brains,include a massive loss of the grey matter in the neocortex,extracellular deposition of amyloid-β(Aβ)in the form of senile plaques and cerebrovascular amyloid angiopathy,and intra-neuronal accumulation of neurofibrillary tangles,formed by hyper-phosphorylated tau protein.展开更多
The cortical grey matter of mammals has a specific cyto-architecture defined by the process of "tiling" in which protoplasmic astrocytes parcellate the nervous tissue into spatially segregated territorial do...The cortical grey matter of mammals has a specific cyto-architecture defined by the process of "tiling" in which protoplasmic astrocytes parcellate the nervous tissue into spatially segregated territorial domains.展开更多
Newts have impressive regenerative capabilities,but it remains unclear about the role of epigenetic regulation in regeneration process.We herein investigated histone modifications in newt tail tissue cells following a...Newts have impressive regenerative capabilities,but it remains unclear about the role of epigenetic regulation in regeneration process.We herein investigated histone modifications in newt tail tissue cells following amputation.lberian ribbed newts(6-8 months old)were suffered to about 1.5 cm length of amputation of their tails for initiating regeneration process,and the residual stump of tail tissues were collected for immunohistochemical analysis 3 days later.Compared to the tissue cells of intact tails,c Kit positive stem cells and PCNA positive proliferating cells were significantly higher in tails suffered to amputation.Amputation also significantly induced the acetylation of H3K9,H3K14 and H3K27 in cells of the tails with amputation,but did not significantly change the methylation of H3K27.These results suggest that epigenetic regulation likely involves in newt tail regeneration following amputation.展开更多
The blood-brain barrier(BBB)(discovered and defined by Max Lewandowsky and Lina Stern,and not,as it is universally,and yet erroneously believed,by Paul Ehrlich(Verkhratsky and Pivoriunas,2023))that separates the nervo...The blood-brain barrier(BBB)(discovered and defined by Max Lewandowsky and Lina Stern,and not,as it is universally,and yet erroneously believed,by Paul Ehrlich(Verkhratsky and Pivoriunas,2023))that separates the nervous system from the circulation is evolutionarily conserved from arthropods to man.The primeval BBB of the invertebrates and some early vertebrates was made solely by glial cells and secured(in invertebrates)by septate junctions.展开更多
Exosome-based treatments are gaining traction as a viable approach to addressing the various issues faced by an ischemic stroke.These extracellular vesicles,mainly produced by mesenchymal stem cells,exhibit many prope...Exosome-based treatments are gaining traction as a viable approach to addressing the various issues faced by an ischemic stroke.These extracellular vesicles,mainly produced by mesenchymal stem cells,exhibit many properties with substantial therapeutic potential.Exosomes are particularly appealing for stroke therapy because of their low immunogenicity,effective cargo transport,and ability to cross the blood–brain barrier.Their diverse effects include neuroprotection,angiogenesis stimulation,inflammatory response modulation,and cell death pathway attenuation,synergistically promoting neuronal survival,tissue regeneration,and functional recovery.Exosomes also show potential as diagnostic indicators for early stroke identification and customized treatment options.Despite these promising qualities,current exosome-based therapeutics have some limitations.The heterogeneity of exosome release among cell types,difficulty in standardization and isolation techniques,and complications linked to dosage and targeted administration necessitates extensive investigation.It is critical to thoroughly understand exosomal processes and their complicated interactions within the cellular milieu.To improve the practicality and efficacy of exosome-based medicines,research efforts must focus on improving production processes,developing robust evaluation criteria,and developing large-scale isolation techniques.Altogether,exosomes’multifunctional properties offer a new route for transforming stroke treatment and significantly improving patient outcomes.展开更多
It is generally accepted that a severed spinal cord is associated with permanent paralysis.Recently,a spinal cord fusion protocol(GEMINI)has been proposed,whereby an acutely controlled,sharp,operative transection of t...It is generally accepted that a severed spinal cord is associated with permanent paralysis.Recently,a spinal cord fusion protocol(GEMINI)has been proposed,whereby an acutely controlled,sharp,operative transection of the spinal cord is carried out.This scenario is not comparable(even in principle)to the clinical situation of a traumatic展开更多
A sharply transected spinal cord has been shown to be fused under the accelerating influence of membrane fusogens such as polyethylene glycol(PEG)(GEMINI protocol). Previous work provided evidence that this is in fact...A sharply transected spinal cord has been shown to be fused under the accelerating influence of membrane fusogens such as polyethylene glycol(PEG)(GEMINI protocol). Previous work provided evidence that this is in fact possible. Other fusogens might improve current results. In this study, we aimed to assess the effects of PEGylated graphene nanoribons(PEG-GNR, and called "Texas PEG" when prepared as 1 wt% dispersion in PEG600) versus placebo(saline) on locomotor function recovery and cellular level in a rat model of spinal cord transection at lumbar segment 1(L_1) level. In vivo and in vitro experiments(n = 10 per experiment) were designed. In the in vivo experiment, all rats were submitted to full spinal cord transection at L_1 level. Five weeks later, behavioral assessment was performed using the Basso Beattie Bresnahan(BBB) locomotor rating scale. Immunohistochemical staining with neuron marker neurofilament 200(NF200) antibody and astrocytic scar marker glial fibrillary acidic protein(GFAP) was also performed in the injured spinal cord. In the in vitro experiment, the effects of Texas PEG application for 72 hours on the neurite outgrowth of SH-SY5 Y cells were observed under the inverted microscope. Results of both in vivo and in vitro experiments suggest that Texas PEG reduces the formation of glial scars, promotes the regeneration of neurites, and thereby contributes to the recovery of locomotor function of a rat model of spinal cord transfection.展开更多
BACKGROUND ATP-sensitive K^+(KATP)channels were originally found in cardiac myocytes by Noma in 1983.KATP channels were formed by potassium ion-passing poreforming subunits(Kir6.1,Kir6.2)and regulatory subunits SUR1,S...BACKGROUND ATP-sensitive K^+(KATP)channels were originally found in cardiac myocytes by Noma in 1983.KATP channels were formed by potassium ion-passing poreforming subunits(Kir6.1,Kir6.2)and regulatory subunits SUR1,SU2A and SUR2B.A number of cells and tissues have been revealed to contain these channels including hepatocytes,but detailed localization of these subunits in different types of liver cells was still uncertain.AIM To investigate the expression of KATP channel subunits in rat liver and their localization in different cells of the liver.METHODS Rabbit anti-rat SUR1 peptide antibody was raised and purified by antigen immunoaffinity column chromatography.Four of Sprague-Dawley rats were used for liver protein extraction for immunoblot analysis,seven of them were used for immunohistochemistry both for the ABC method and immunofluorescence staining.Four of Wistar rats were used for the isolation of hepatic stellate cells(HSCs)and Kupffer cells for both primary culture and immunocytochemistry.RESULTS Immunoblot analysis showed that the five kinds of KATP channel subunits,i.e.Kir6.1,Kir6.2,SUR1,SUR2A,and SUR2B,were detected in liver.Immunohistochemical staining showed that Kir6.1 and Kir6.2 were weakly to moderately expressed in parenchymal cells and sinusoidal lining cells,while SUR1,SUR2A,and SUR2B were mainly localized to sinusoidal lining cells,such as HSCs,Kupffer cells,and sinusoidal endothelial cells.Immunoreactivity for SUR2A and SUR2B was expressed in the hepatocyte membrane.Double immunofluorescence staining further showed that the pore-forming subunits Kir6.1 and/or Kir6.2 colocalized with GFAP in rat liver sections and primary cultured HSCs.These KATP channel subunits also colocalized with CD68 in liver sections and primary cultured Kupffer cells.The SUR subunits colocalized with GFAP in liver sections and colocalized with CD68 both in liver sections and primary cultured Kupffer cells.In addition,five KATP channel subunits colocalized with SE-1 in sinusoidal endothelial cells.CONCLUSION Observations from the present study indicated that KATP channel subunits expressed in rat liver and the diversity of KATP channel subunit composition might form different types of KATP channels.This is applicable to hepatocytes,HSCs,various types of Kupffer cells and sinusoidal endothelial cells.展开更多
The functional realization is the most important problem in vascular tissue engineering. The small-caliber blood vessel substitutes are prone to thrombi, which results in functional loss of blood vessels. However, thi...The functional realization is the most important problem in vascular tissue engineering. The small-caliber blood vessel substitutes are prone to thrombi, which results in functional loss of blood vessels. However, this is probably due to the imper- fection of endothelial layer in the substitutes. In this study, MSCs were seeded on a series of porous PLGA films with various porosity and pore size made by sodium chloride (NaCl) particulate leaching, and cell proliferation on each film was inspected. The film made of the 75% (w/w) particulate proportion and 30―50 μm pore size maximized the proliferation rate and was chosen as the scaffolds for the differentia- tion of MSCs into endothelial cells. The induced cells expressed endothelial cells specific Flk-1, Ⅷ factor and CD34, possessed endothelial cells specific Weible-palade (W-P) body, and had the abilities of ingesting low density lipoprotein and secreting prostacyclin (PGI2). The results show that MSCs not only have the ideal biological compatibility with the porous PLGA films, but also have the potency of dif- ferentiating into functional endothelial cells, whichshould facilitate the endothelialization in vascular tissue engineering.展开更多
Embryonic stem cells(ESCs) maintain their cellular identity through the systematic regulation of master transcription factors and chromatin remodeling complexes. Recent work has shown that the unusually large-scale en...Embryonic stem cells(ESCs) maintain their cellular identity through the systematic regulation of master transcription factors and chromatin remodeling complexes. Recent work has shown that the unusually large-scale enhancers—namely super-enhancers(SEs), on which BRD4, a member of the bromodomain and extraterminal domain(BET) family is highly enriched—could regulate pluripotency-related transcription factors. Moreover, inhibition of BRD4 binding on SEs has been shown to induce the differentiation of ESCs. However, the underlying mechanism of BRD4 inhibition-mediated stem cell differentiation remains elusive. Here we show that both mouse and human ESCs lose their capacity for self-renewal upon treatment with JQ1, a selective inhibitor of BET family including BRD4, with rapid suppression of pluripotency-associated genes. Notably, a high concentration of JQ1 could selectively eliminate ESCs via apoptosis, without affecting the functionality of differentiated somatic cells from ESCs, suggesting that inhibition of BET may have a beneficial effect on the development of pluripotent stem cell-based cell therapy.展开更多
Glioblastomas(GBMs)are highly lethal primary brain tumors.Despite current therapeutic advances in other solid cancers,the treatment of these malignant gliomas remains essentially palliative.GBMs are extremely resistan...Glioblastomas(GBMs)are highly lethal primary brain tumors.Despite current therapeutic advances in other solid cancers,the treatment of these malignant gliomas remains essentially palliative.GBMs are extremely resistant to conventional radiation and chemotherapies.We and others have demonstrated that a highly tumorigenic subpopulation of cancer cells called GBM stem cells(GSCs)promotes therapeutic resistance.We also found that GSCs stimulate tumor angiogenesis by expressing elevated levels of VEGF and contribute to tumor growth,which has been translated into a useful therapeutic strategy in the treatment of recurrent or progressive GBMs.Furthermore,stem cell-like cancer cells(cancer stem cells)have been shown to promote metastasis.Although GBMs rarely metastasize beyond the central nervous system,these highly infiltrative cancers often invade into normal brain tissues preventing surgical resection,and GSCs display an aggressive invasive phenotype.These studies suggest that targeting GSCs may effectively reduce tumor recurrence and significantly improve GBM treatment.Recent studies indicate that cancer stem cells share core signaling pathways with normal somatic or embryonic stem cells,but also display critical distinctions that provide important clues into useful therapeutic targets.In this review,we summarize the current understanding and advances in glioma stem cell research,and discuss potential targeting strategies for future development of anti-GSC therapies.展开更多
Extracellular vesicles(EVs)are tiny biological nanovesicles ranging from approximately 30–1000 nm in diameter that are released into the extracellular matrix of most cell types and in biofluids.The classification of ...Extracellular vesicles(EVs)are tiny biological nanovesicles ranging from approximately 30–1000 nm in diameter that are released into the extracellular matrix of most cell types and in biofluids.The classification of EVs includes exosomes,microvesicles,and apoptotic bodies,dependent on various factors such as size,markers,and biogenesis pathways.The transition of EV relevance from that of being assumed as a trash bag to be a key player in critical physiological and pathological conditions has been revolutionary in many ways.EVs have been recently revealed to play a crucial role in stem cell biology and cancer progression via intercellular communication,contributing to organ development and the progression of cancer.This review focuses on the significant research progress made so far in the role of the crosstalk between EVs and stem cells and their niche,and cellular communication among different germ layers in developmental biology.In addition,it discusses the role of EVs in cancer progression and their application as therapeutic agents or drug delivery vehicles.All such discoveries have been facilitated by tremendous technological advancements in EV-associated research,especially the microfluidics systems.Their pros and cons in the context of characterization of EVs are also extensively discussed in this review.This review also deliberates the role of EVs in normal cell processes and disease conditions,and their application as a diagnostic and therapeutic tool.Finally,we propose future perspectives for EV-related research in stem cell and cancer biology.展开更多
Once neurons are lost because of injury or degeneration,they hardly ever regenerate in most mammalian central nervous system(CNS)regions.In adult rodents,some brain regions,such as the subventricular zone of the later...Once neurons are lost because of injury or degeneration,they hardly ever regenerate in most mammalian central nervous system(CNS)regions.In adult rodents,some brain regions,such as the subventricular zone of the lateral ventricle and the subgranular zone of the dentate gyrus,retain neural stem cells(NSCs)and generate new neurons.Although a small population of new neurons derived from NSCs migrate toward lesion sites after brain injury,they are insufficient to completely restore neuronal functions.Cell transplantation using induced pluripotent stem cells(iPSCs)or embryonic stem cells(ESCs)has become an attractive therapeutic strategy for nerve injury or degeneration(Barker et al.,2015;Huang and Zhang,2019).For Parkinson’s disease,transplantation of dopaminergic neurons from human ESCs or iPSCs is emerging as a therapeutic approach(Li and Chen,2016).However,the risks of immune rejection and tumorigenesis remain substantial drawbacks of this therapeutic approach.展开更多
Uncovering the molecular pathways that drive skeletal repair has been an ongoing challenge. Initial efforts have relied on in vitro assays to identify the key signaling pathways that drive cartilage and bone different...Uncovering the molecular pathways that drive skeletal repair has been an ongoing challenge. Initial efforts have relied on in vitro assays to identify the key signaling pathways that drive cartilage and bone differentiation. While these assays can provide some clues, assessing specific pathways in animal models is critical. Furthermore, definitive proof that a pathway is required for skeletal repair is best provided using genetic tests. Stimulating the Hh(Hedgehog) pathway can promote cartilage and bone differentiation in cell culture assays. In addition, the application of HH protein or various pathway agonists in vivo has a positive influence on bone healing. Until recently, however, genetic proof that the Hh pathway is involved in bone repair has been lacking. Here, we consider both in vitro and in vivo studies that examine the role of Hh in repair and discuss some of the challenges inherent in their interpretation. We also identify needed areas of study considering a new appreciation for the role of cartilage during repair, the variety of cell types that may have differing roles in repair, and the recent availability of powerful lineage tracing techniques. We are optimistic that emerging genetic tools will make it possible to precisely define when and in which cells promoting Hh signaling can best promote skeletal repair, and thus, the clinical potential for targeting the Hh pathway can be realized.展开更多
On April 26-27, 2013, the Step by Step Foundation hosted the Second International Spinal Cord Repair Meeting at the Fira Barcelona Convention Center in Hospitalet de Llobregat, Spain, highlighting some of the exciting...On April 26-27, 2013, the Step by Step Foundation hosted the Second International Spinal Cord Repair Meeting at the Fira Barcelona Convention Center in Hospitalet de Llobregat, Spain, highlighting some of the exciting research including clinical trials which show promise for treatments for this devastating disorder. This meeting brought together clinicians, clinical scientists and molecular biologists from more than 10 countries to evaluate current knowledge on clinical, cellular, and biomolecular aspects of spinal cord injury. A major goal of the conference in advancing the translation of research data to the clinic was to promote multi-pronged approaches for therapy of this complex problem.展开更多
基金supported by a Grant-in-Aid for Scientific Research(B)JP21H02808(to TM)JST SPRING JPMJSP2136(to MI)。
文摘Neural stem cells(NSCs)are the source of all neurons and glial cells(astrocytes and oligodendrocytes)in the central nervous system.The adult mammalian brain retains NSCs in the subgranular zone of the dentate gyrus in the hippocampus and ventricular subventricular zone lining the lateral ventricle(Olpe and Jessberger,2022).Adult NSCs in rodents are preserved throughout life and continuously produce new neurons that integrate into the pre-existing neuronal network.
基金supported by National Research Programme,“Healthy ageing”(Grant No.SEN-15090)from Research Council of Lithuania
文摘Extracellular vesicles(EVs)provide a novel mechanism of intercellular communication via the transfer of proteins,lipids,and miR NAs between cells.It is now widely accepted that cargo content of EVs depends on cell type and its physiological state.Accordingly,EVs derived from healthy cells may have a comparable therapeutic potential as cells themselves.Indeed,several studies confirmed this notion
基金the following financial support grant FAR-2019 to DL from The Universita del Piemonte Orientale。
文摘Alzheimer’s disease(AD)is a major age-related form of dementia with a number of cases exponentially growing,causing enormous social and economic impact on individuals and society.Neuropathological hallmarks of AD,evident in postmortem AD brains,include a massive loss of the grey matter in the neocortex,extracellular deposition of amyloid-β(Aβ)in the form of senile plaques and cerebrovascular amyloid angiopathy,and intra-neuronal accumulation of neurofibrillary tangles,formed by hyper-phosphorylated tau protein.
基金supported by the Global Grant measure (No.09.3.3-LMTK-712-01-0082to AP and AV)。
文摘The cortical grey matter of mammals has a specific cyto-architecture defined by the process of "tiling" in which protoplasmic astrocytes parcellate the nervous tissue into spatially segregated territorial domains.
文摘Newts have impressive regenerative capabilities,but it remains unclear about the role of epigenetic regulation in regeneration process.We herein investigated histone modifications in newt tail tissue cells following amputation.lberian ribbed newts(6-8 months old)were suffered to about 1.5 cm length of amputation of their tails for initiating regeneration process,and the residual stump of tail tissues were collected for immunohistochemical analysis 3 days later.Compared to the tissue cells of intact tails,c Kit positive stem cells and PCNA positive proliferating cells were significantly higher in tails suffered to amputation.Amputation also significantly induced the acetylation of H3K9,H3K14 and H3K27 in cells of the tails with amputation,but did not significantly change the methylation of H3K27.These results suggest that epigenetic regulation likely involves in newt tail regeneration following amputation.
基金funding from European Regional Development Fund(project No 13.1.1-LMT-K-718-05-0005)under grant agreement with the Research Council of Lithuania(LMTLT)。
文摘The blood-brain barrier(BBB)(discovered and defined by Max Lewandowsky and Lina Stern,and not,as it is universally,and yet erroneously believed,by Paul Ehrlich(Verkhratsky and Pivoriunas,2023))that separates the nervous system from the circulation is evolutionarily conserved from arthropods to man.The primeval BBB of the invertebrates and some early vertebrates was made solely by glial cells and secured(in invertebrates)by septate junctions.
基金National Institutes of Health,Grant/Award Number:NIH R21NS133531。
文摘Exosome-based treatments are gaining traction as a viable approach to addressing the various issues faced by an ischemic stroke.These extracellular vesicles,mainly produced by mesenchymal stem cells,exhibit many properties with substantial therapeutic potential.Exosomes are particularly appealing for stroke therapy because of their low immunogenicity,effective cargo transport,and ability to cross the blood–brain barrier.Their diverse effects include neuroprotection,angiogenesis stimulation,inflammatory response modulation,and cell death pathway attenuation,synergistically promoting neuronal survival,tissue regeneration,and functional recovery.Exosomes also show potential as diagnostic indicators for early stroke identification and customized treatment options.Despite these promising qualities,current exosome-based therapeutics have some limitations.The heterogeneity of exosome release among cell types,difficulty in standardization and isolation techniques,and complications linked to dosage and targeted administration necessitates extensive investigation.It is critical to thoroughly understand exosomal processes and their complicated interactions within the cellular milieu.To improve the practicality and efficacy of exosome-based medicines,research efforts must focus on improving production processes,developing robust evaluation criteria,and developing large-scale isolation techniques.Altogether,exosomes’multifunctional properties offer a new route for transforming stroke treatment and significantly improving patient outcomes.
基金supported by the National Research Foundation of Korea(NRF),No.2015R1C1A1A02037047
文摘It is generally accepted that a severed spinal cord is associated with permanent paralysis.Recently,a spinal cord fusion protocol(GEMINI)has been proposed,whereby an acutely controlled,sharp,operative transection of the spinal cord is carried out.This scenario is not comparable(even in principle)to the clinical situation of a traumatic
基金supported by a grant from the National Research Foundation(NRF)funded by the Korean government(NRF-2015M3A9C7030091 and NRF-2015R1C1A1A02037047)
文摘A sharply transected spinal cord has been shown to be fused under the accelerating influence of membrane fusogens such as polyethylene glycol(PEG)(GEMINI protocol). Previous work provided evidence that this is in fact possible. Other fusogens might improve current results. In this study, we aimed to assess the effects of PEGylated graphene nanoribons(PEG-GNR, and called "Texas PEG" when prepared as 1 wt% dispersion in PEG600) versus placebo(saline) on locomotor function recovery and cellular level in a rat model of spinal cord transection at lumbar segment 1(L_1) level. In vivo and in vitro experiments(n = 10 per experiment) were designed. In the in vivo experiment, all rats were submitted to full spinal cord transection at L_1 level. Five weeks later, behavioral assessment was performed using the Basso Beattie Bresnahan(BBB) locomotor rating scale. Immunohistochemical staining with neuron marker neurofilament 200(NF200) antibody and astrocytic scar marker glial fibrillary acidic protein(GFAP) was also performed in the injured spinal cord. In the in vitro experiment, the effects of Texas PEG application for 72 hours on the neurite outgrowth of SH-SY5 Y cells were observed under the inverted microscope. Results of both in vivo and in vitro experiments suggest that Texas PEG reduces the formation of glial scars, promotes the regeneration of neurites, and thereby contributes to the recovery of locomotor function of a rat model of spinal cord transfection.
基金Supported by the Program of the network-type joint Usage/Research Center for Radiation Disaster Medical Science of Hiroshima University,Nagasaki University,and Fukushima Medical University
文摘BACKGROUND ATP-sensitive K^+(KATP)channels were originally found in cardiac myocytes by Noma in 1983.KATP channels were formed by potassium ion-passing poreforming subunits(Kir6.1,Kir6.2)and regulatory subunits SUR1,SU2A and SUR2B.A number of cells and tissues have been revealed to contain these channels including hepatocytes,but detailed localization of these subunits in different types of liver cells was still uncertain.AIM To investigate the expression of KATP channel subunits in rat liver and their localization in different cells of the liver.METHODS Rabbit anti-rat SUR1 peptide antibody was raised and purified by antigen immunoaffinity column chromatography.Four of Sprague-Dawley rats were used for liver protein extraction for immunoblot analysis,seven of them were used for immunohistochemistry both for the ABC method and immunofluorescence staining.Four of Wistar rats were used for the isolation of hepatic stellate cells(HSCs)and Kupffer cells for both primary culture and immunocytochemistry.RESULTS Immunoblot analysis showed that the five kinds of KATP channel subunits,i.e.Kir6.1,Kir6.2,SUR1,SUR2A,and SUR2B,were detected in liver.Immunohistochemical staining showed that Kir6.1 and Kir6.2 were weakly to moderately expressed in parenchymal cells and sinusoidal lining cells,while SUR1,SUR2A,and SUR2B were mainly localized to sinusoidal lining cells,such as HSCs,Kupffer cells,and sinusoidal endothelial cells.Immunoreactivity for SUR2A and SUR2B was expressed in the hepatocyte membrane.Double immunofluorescence staining further showed that the pore-forming subunits Kir6.1 and/or Kir6.2 colocalized with GFAP in rat liver sections and primary cultured HSCs.These KATP channel subunits also colocalized with CD68 in liver sections and primary cultured Kupffer cells.The SUR subunits colocalized with GFAP in liver sections and colocalized with CD68 both in liver sections and primary cultured Kupffer cells.In addition,five KATP channel subunits colocalized with SE-1 in sinusoidal endothelial cells.CONCLUSION Observations from the present study indicated that KATP channel subunits expressed in rat liver and the diversity of KATP channel subunit composition might form different types of KATP channels.This is applicable to hepatocytes,HSCs,various types of Kupffer cells and sinusoidal endothelial cells.
文摘The functional realization is the most important problem in vascular tissue engineering. The small-caliber blood vessel substitutes are prone to thrombi, which results in functional loss of blood vessels. However, this is probably due to the imper- fection of endothelial layer in the substitutes. In this study, MSCs were seeded on a series of porous PLGA films with various porosity and pore size made by sodium chloride (NaCl) particulate leaching, and cell proliferation on each film was inspected. The film made of the 75% (w/w) particulate proportion and 30―50 μm pore size maximized the proliferation rate and was chosen as the scaffolds for the differentia- tion of MSCs into endothelial cells. The induced cells expressed endothelial cells specific Flk-1, Ⅷ factor and CD34, possessed endothelial cells specific Weible-palade (W-P) body, and had the abilities of ingesting low density lipoprotein and secreting prostacyclin (PGI2). The results show that MSCs not only have the ideal biological compatibility with the porous PLGA films, but also have the potency of dif- ferentiating into functional endothelial cells, whichshould facilitate the endothelialization in vascular tissue engineering.
基金supported by the National Research Foundation of Korea(NRF-2016K1A3A1A61006005,NRF-2016R1A2B3011860,NRF-2016R1A5A2012284,and NRF-2017M3C7A1047640)
文摘Embryonic stem cells(ESCs) maintain their cellular identity through the systematic regulation of master transcription factors and chromatin remodeling complexes. Recent work has shown that the unusually large-scale enhancers—namely super-enhancers(SEs), on which BRD4, a member of the bromodomain and extraterminal domain(BET) family is highly enriched—could regulate pluripotency-related transcription factors. Moreover, inhibition of BRD4 binding on SEs has been shown to induce the differentiation of ESCs. However, the underlying mechanism of BRD4 inhibition-mediated stem cell differentiation remains elusive. Here we show that both mouse and human ESCs lose their capacity for self-renewal upon treatment with JQ1, a selective inhibitor of BET family including BRD4, with rapid suppression of pluripotency-associated genes. Notably, a high concentration of JQ1 could selectively eliminate ESCs via apoptosis, without affecting the functionality of differentiated somatic cells from ESCs, suggesting that inhibition of BET may have a beneficial effect on the development of pluripotent stem cell-based cell therapy.
文摘Glioblastomas(GBMs)are highly lethal primary brain tumors.Despite current therapeutic advances in other solid cancers,the treatment of these malignant gliomas remains essentially palliative.GBMs are extremely resistant to conventional radiation and chemotherapies.We and others have demonstrated that a highly tumorigenic subpopulation of cancer cells called GBM stem cells(GSCs)promotes therapeutic resistance.We also found that GSCs stimulate tumor angiogenesis by expressing elevated levels of VEGF and contribute to tumor growth,which has been translated into a useful therapeutic strategy in the treatment of recurrent or progressive GBMs.Furthermore,stem cell-like cancer cells(cancer stem cells)have been shown to promote metastasis.Although GBMs rarely metastasize beyond the central nervous system,these highly infiltrative cancers often invade into normal brain tissues preventing surgical resection,and GSCs display an aggressive invasive phenotype.These studies suggest that targeting GSCs may effectively reduce tumor recurrence and significantly improve GBM treatment.Recent studies indicate that cancer stem cells share core signaling pathways with normal somatic or embryonic stem cells,but also display critical distinctions that provide important clues into useful therapeutic targets.In this review,we summarize the current understanding and advances in glioma stem cell research,and discuss potential targeting strategies for future development of anti-GSC therapies.
基金U.S.National Institute of Health(4R00CA226353-02 to H J.Chen)Hong Kong Health and Medical Research Fund(HMRF:No.:06172956 to Q.L)+1 种基金Stem Cell and Regenerative Medicine Fund(Guangzhou Women and Children’s Medical Centre,Grant No.:5001-4001010 to Q.L)Research Grants Council Theme-based Research Scheme(TRS:No.T12-703-19R to Q.L.).
文摘Extracellular vesicles(EVs)are tiny biological nanovesicles ranging from approximately 30–1000 nm in diameter that are released into the extracellular matrix of most cell types and in biofluids.The classification of EVs includes exosomes,microvesicles,and apoptotic bodies,dependent on various factors such as size,markers,and biogenesis pathways.The transition of EV relevance from that of being assumed as a trash bag to be a key player in critical physiological and pathological conditions has been revolutionary in many ways.EVs have been recently revealed to play a crucial role in stem cell biology and cancer progression via intercellular communication,contributing to organ development and the progression of cancer.This review focuses on the significant research progress made so far in the role of the crosstalk between EVs and stem cells and their niche,and cellular communication among different germ layers in developmental biology.In addition,it discusses the role of EVs in cancer progression and their application as therapeutic agents or drug delivery vehicles.All such discoveries have been facilitated by tremendous technological advancements in EV-associated research,especially the microfluidics systems.Their pros and cons in the context of characterization of EVs are also extensively discussed in this review.This review also deliberates the role of EVs in normal cell processes and disease conditions,and their application as a diagnostic and therapeutic tool.Finally,we propose future perspectives for EV-related research in stem cell and cancer biology.
基金This work is supported by Grant-in-Aid for Young Scientists(B)JP18K14820(to TM)Medical Care Education Research Foundation(to HS).
文摘Once neurons are lost because of injury or degeneration,they hardly ever regenerate in most mammalian central nervous system(CNS)regions.In adult rodents,some brain regions,such as the subventricular zone of the lateral ventricle and the subgranular zone of the dentate gyrus,retain neural stem cells(NSCs)and generate new neurons.Although a small population of new neurons derived from NSCs migrate toward lesion sites after brain injury,they are insufficient to completely restore neuronal functions.Cell transplantation using induced pluripotent stem cells(iPSCs)or embryonic stem cells(ESCs)has become an attractive therapeutic strategy for nerve injury or degeneration(Barker et al.,2015;Huang and Zhang,2019).For Parkinson’s disease,transplantation of dopaminergic neurons from human ESCs or iPSCs is emerging as a therapeutic approach(Li and Chen,2016).However,the risks of immune rejection and tumorigenesis remain substantial drawbacks of this therapeutic approach.
基金supported by NICHD T32 training grants(S.T.K.,S.L.,M.S.)the Roy E.Thomas Graduate Scholarship(M.S.)by NIAMS AR069700(F.V.M).
文摘Uncovering the molecular pathways that drive skeletal repair has been an ongoing challenge. Initial efforts have relied on in vitro assays to identify the key signaling pathways that drive cartilage and bone differentiation. While these assays can provide some clues, assessing specific pathways in animal models is critical. Furthermore, definitive proof that a pathway is required for skeletal repair is best provided using genetic tests. Stimulating the Hh(Hedgehog) pathway can promote cartilage and bone differentiation in cell culture assays. In addition, the application of HH protein or various pathway agonists in vivo has a positive influence on bone healing. Until recently, however, genetic proof that the Hh pathway is involved in bone repair has been lacking. Here, we consider both in vitro and in vivo studies that examine the role of Hh in repair and discuss some of the challenges inherent in their interpretation. We also identify needed areas of study considering a new appreciation for the role of cartilage during repair, the variety of cell types that may have differing roles in repair, and the recent availability of powerful lineage tracing techniques. We are optimistic that emerging genetic tools will make it possible to precisely define when and in which cells promoting Hh signaling can best promote skeletal repair, and thus, the clinical potential for targeting the Hh pathway can be realized.
文摘On April 26-27, 2013, the Step by Step Foundation hosted the Second International Spinal Cord Repair Meeting at the Fira Barcelona Convention Center in Hospitalet de Llobregat, Spain, highlighting some of the exciting research including clinical trials which show promise for treatments for this devastating disorder. This meeting brought together clinicians, clinical scientists and molecular biologists from more than 10 countries to evaluate current knowledge on clinical, cellular, and biomolecular aspects of spinal cord injury. A major goal of the conference in advancing the translation of research data to the clinic was to promote multi-pronged approaches for therapy of this complex problem.
