PPeritendinous adhesion formation(PAF)can substantially limit the range of motion of digits.However,the origin of myofibroblasts in PAF tissues is still unclear.In this study,we found that the concentration of active ...PPeritendinous adhesion formation(PAF)can substantially limit the range of motion of digits.However,the origin of myofibroblasts in PAF tissues is still unclear.In this study,we found that the concentration of active TGF-β1 and the numbers of macrophages,mesenchymal stromal cells(MSCs),and myofibroblasts in human and mouse adhesion tissues were increased.Furthermore,knockout of TGF-β1 in macrophages or TGF-β1R2 in MSCs inhibited PAF by reducing MSC and myofibroblast infiltration and collagenⅠandⅢdeposition,respectively.Moreover,we found that MSCs differentiated into myofibroblasts to form adhesion tissues.Systemic injection of the TGF-β–neutralizing antibody 1D11 during the granulation formation stage of PAF significantly reduced the infiltration of MSCs and myofibroblasts and,subsequently,PAF.These results suggest that macrophage-derived TGF-β1 recruits MSCs to form myofibroblasts in peritendinous adhesions.An improved understanding of PAF mechanisms could help identify a potential therapeutic strategy.展开更多
Adiponectin is the most abundant circulating adipokine and is primarily involved in glucose metabolism and insulin resistance.Within the bone,osteoblasts and osteoclasts express the adiponectin receptors,however,there...Adiponectin is the most abundant circulating adipokine and is primarily involved in glucose metabolism and insulin resistance.Within the bone,osteoblasts and osteoclasts express the adiponectin receptors,however,there are conflicting reports on the effects of adiponectin on bone formation and turnover.Many studies have shown a pro-osteogenic role for adiponectin in in vivo murine models and in vitro:with increased osteoblast differentiation and activity,alongside lower levels of osteoclastogenesis.However,human studies often demonstrate an inverse relationship between adiponectin concentration and bone activity.Moreover,the presence of multiple isoforms of adiponectin and multiple receptor subtypes has the potential to lead to more complex signalling and functional consequences.As such,we still do not fully understand the importance of the adiponectin signalling pathway in regulating bone homeostasis and repair in health,with age and in disease.In this review,we explore our current understanding of adiponectin bioactivity in the bone;the significance of its different isoforms;and how adiponectin biology is altered in disease.Ultimately,furthering our understanding of adiponectin regulation of bone biology is key to developing pharmacological and non-pharmacological(lifestyle)interventions that target adiponectin signalling to boost bone growth and repair in healthy ageing,following injury or in disease.展开更多
The effects of vitamin D on osteoblast mineralization are well documented. Reports of the effects of vitamin D on osteoclasts, however, are conflicting, showing both inhibition and stimulation. Finding that resorbing ...The effects of vitamin D on osteoblast mineralization are well documented. Reports of the effects of vitamin D on osteoclasts, however, are conflicting, showing both inhibition and stimulation. Finding that resorbing osteoclasts in human bone express vitamin D receptor (VDR), we examined their response to different concentrations of 25-hydroxy vitamin D3 [25(OH)D3] (100 or 500 nmol·L^-1) and 1,25-dihydroxy vitamin D3 [1,25(OH)2D3] (0.1 or 0.5 nmol·L^-1) metabolites in cell cultures. Specifically, CD14+ monocytes were cultured in charcoal-stripped serum in the presence of receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Tartrate-resistant acid phosphatase (TRAP) histochemical staining assays and dentine resorption analysis were used to identify the size and number of osteoclast cells, number of nuclei per cell and resorption activity. The expression of VDR was detected in human bone tissue (ex vivo) by immunohistochemistry and in vitro cell cultures by western blotting. Quantitative reverse transcription-PCR (qRT-PCR) was used to determine the level of expression of vitamin D-related genes in response to vitamin D metabolites. VDR-related genes during osteoclastogenesis, shown by qRT-PCR, was stimulated in response to 500 nmol·L^-1 of 25(OH)D3 and 0.1-0.5 nmol·L^-1 of 1,25(OH)2D3, upregulating cytochrome P450 family 27 subfamily B member I (CYP27B1) and cytochrome P450 family 24 subfamily A member I (CYP24A1). Osteoclast fusion transcripts transmembrane 7 subfamily member 4 (tm7sf4) and nuclear factor of activated T-cell cytoplasmic 1 (nfatcl) where downregulated in response to vitamin D metabolites. Osteoclast number and resorption activity were also increased. Both 25(OH)D3 and 1,25(OH)2D3 reduced osteoclast size and number when co-treated with RANKL and M-CSF. The evidence for VDR expression in resorbing osteoclasts in vivo and low-dose effects of 1,25(OH)2D3 on osteoclasts in vitro may therefore provide insight into the effects of clinical vitamin D treatments, further providing a counterpoint to the high-dose effects reported from in vitro experiments.展开更多
BACKGROUND The conventional implant approach involves flap elevation,which may result in increased soft tissue and bone loss and postoperative morbidity.The flapless surgical technique,aided by three-dimensional medic...BACKGROUND The conventional implant approach involves flap elevation,which may result in increased soft tissue and bone loss and postoperative morbidity.The flapless surgical technique,aided by three-dimensional medical imaging equipment,is regarded as a possible alternative to the conventional approach to alleviate the above issues.Several studies have been performed regarding the role of flapless implant surgery.However,the results are inconsistent and there is no robust synthesis of long-term evidence to better inform surgeons regarding which type of surgical technique is more beneficial to the long-term prognosis of patients in need of implant insertion.AIM To compare the long-term clinical performance after flapless implant surgery to that after the conventional approach with flap elevation.METHODS PubMed,EMBASE,Cochrane Central Register of Controlled Trials,and grey literature databases were searched from inception to 23 September 2019.Randomised controlled trials(RCTs)and cohort studies comparing the long-term clinical performance after flapless implant surgery to that after the conventional approach over a follow-up of three years or more were included.Meta-analyses were conducted to estimate the odds ratios(ORs)or mean differences(MDs)and their 95%confidence intervals(CIs)between the long-term implant survival rate,marginal bone loss,and complication rate of the flapless and conventional groups.Subgroup analyses were carried out to account for the possible effects of the guided or free-hand method during flapless surgery.RESULTS Ten articles,including four RCTs and six cohort studies,satisfied the eligibility criteria and nine of them were included in the meta-analysis.There was no significant difference between the long-term implant survival rate[OR=1.30,95%CI(0.37,4.54),P=0.68],marginal bone loss[MD=0.01,95%CI(-0.42,0.44),P=0.97],and complication rate[OR=1.44,95%CI(0.77,2.68),P=0.25]after flapless implant surgery and the conventional approach.Moreover,subgroup analyses revealed that there was no statistically significant difference between the implant survival rate[guided:OR=1.52,95%CI(0.19,12.35),P=0.70];free-hand:n=1,could not be estimated,marginal bone loss[guided:MD=0.22,95%CI(-0.14,0.59),P=0.23;free-hand:MD=-0.27,95%CI(-1.10,0.57),P=0.53],or complication rate[guided:OR=1.16,95%CI(0.52,2.63),P=0.71;free-hand:OR=1.75,95%CI(0.66,4.63),P=0.26]in the flapless and conventional groups either with use of the surgical guide or by the free-hand method.CONCLUSION The flapless surgery and conventional approach had comparable clinical performance over three years or more.The guided or free-hand technique does not significantly affect the long-term outcomes of flapless surgery.展开更多
Glucocorticoids remain the cornerstone of medicaltherapy in giant cell arteritis(GCA) and should be started immediately to prevent severe consequences of the disease, such as blindness. However, glucocorticoid therapy...Glucocorticoids remain the cornerstone of medicaltherapy in giant cell arteritis(GCA) and should be started immediately to prevent severe consequences of the disease, such as blindness. However, glucocorticoid therapy leads to significant toxicity in over 80% of the patients. Various steroid-sparing agents have been tried, but robust scientific evidence of their efficacy and safety is still lacking. Tocilizumab, a monoclonal IL-6 receptor blocker, has shown promising results in a number of case series and is now being tested in a multi-centre randomized controlled trial. Other targeted treatments, such as the use of abatacept, are also now under investigation in GCA. The need for surgical treatment is rare and should ideally be performed in a quiescent phase of the disease. Not all patients follow the same course, but there are no valid biomarkers to assess therapy response. Monitoring of disease progress still relies on assessing clinical features and measuring inflammatory markers(C-reactive protein and erythrocyte sedimentation rate). Imaging techniques(e.g., ultrasound) are clearly important screening tools for aortic aneurysms and assessing patients with largevessel involvement, but may also have an important role as biomarkers of disease activity over time or in response to therapy. Although GCA is the most common form of primary vasculitis, the optimal strategies for treatment and monitoring remain uncertain.展开更多
“It is the responsibility of everyone involved to ensure that the published record is an unbiased,accurate representation of research”[1].The research record is often manipulated for short term gain but at the risk ...“It is the responsibility of everyone involved to ensure that the published record is an unbiased,accurate representation of research”[1].The research record is often manipulated for short term gain but at the risk of harm to patients.The medical research community needs to implement changes to ensure that readers obtain the truth about all research,especially reports of randomised trials,which hold a special place in answering what works best for patients.展开更多
In all aspects of communication the meanings of words and definitions are of paramount importance for clear understanding and transmission of ideas.However,these meanings may change with time so that words and phrases...In all aspects of communication the meanings of words and definitions are of paramount importance for clear understanding and transmission of ideas.However,these meanings may change with time so that words and phrases take on different interpretations.Furthermore,the way words are used in writing significantly affects the conveyance of ideas from one mind to another.1 In the long history of the study of the histogenesis of bone we see some of these changes in meaning and understanding of concepts that have perhaps contributed to serious misinterpretation of the ideas of some investigators in the field.It is hoped that this brief historical perspective may explain and clarify at least some of the problems that have resulted.展开更多
Despite being over thirty years since there was proof that the hypothetical osteogenic stem cell existed,1 demonstration of any dramatic value for the use of such cells in orthopaedic clinical practice by tissue engin...Despite being over thirty years since there was proof that the hypothetical osteogenic stem cell existed,1 demonstration of any dramatic value for the use of such cells in orthopaedic clinical practice by tissue engineering approaches has not yet been realised.This is notwithstanding extensive studies concerning the likely nature and potentials of these cells in countless in vitro and in vivo investigations.In part,this is based on the confusion caused by exaggeration of claims by unreliable,or at best naïve,investigators and opportunistic entrepreneurs who have grossly misinterpreted data from many ill-conceived studies.2,3 This pseudo-science has been harmful,especially to the stem cell field,both academically and commercially.展开更多
For successful translational use of stem cells in biomedicine,knowledge of the quality of the cells,the presence of bioactive factors,and the nature of the microenvironmental niches is paramount.They may be regarded a...For successful translational use of stem cells in biomedicine,knowledge of the quality of the cells,the presence of bioactive factors,and the nature of the microenvironmental niches is paramount.They may be regarded as the Three Musketeers as they unite“All for one,one for all”1 to control the trafficking,survival,proliferation,and differentiation of stem cells.In this second themed issue of Biomaterials Translational,entitled“Application of Stem Cells in Translational Medicine:Stem Cells Part II”.展开更多
Dedifferentiation of cell identity to a progenitor-like or stem cell-like state with increased cellular plasticity is frequently observed in cancer formation.During this process,a subpopulation of cells in tumours acq...Dedifferentiation of cell identity to a progenitor-like or stem cell-like state with increased cellular plasticity is frequently observed in cancer formation.During this process,a subpopulation of cells in tumours acquires a stem cell-like state partially resembling to naturally occurring pluripotent stem cells that are temporarily present during early embryogenesis.Such characteristics allow these cancer stem cells(CSCs)to give rise to the whole tumour with its entire cellular heterogeneity and thereby support metastases formation while being resistant to current cancer therapeutics.Cancer development and progression are demarcated by transcriptional dysregulation.In this article,we explore the epigenetic mechanisms shaping gene expression during tumorigenesis and cancer stem cell formation,with an emphasis on 3D chromatin architecture.Comparing the pluripotent stem cell state and epigenetic reprogramming to dedifferentiation in cellular transformation provides intriguing insight to chromatin dynamics.We suggest that the 3D chromatin architecture could be used as a target for re-sensitizing cancer stem cells to therapeutics.展开更多
Tendon disease is a significant and growing burden to healthcare systems.One strategy to address this challenge is tssueengineering.A widely held view in this feld is that mechanical stimulation provided to constructs...Tendon disease is a significant and growing burden to healthcare systems.One strategy to address this challenge is tssueengineering.A widely held view in this feld is that mechanical stimulation provided to constructs should replicate themechanicaienvironment of native tissue as closely as possible.We review recent tendon tissue engineering studies inthisarticle and highlight limitations of conventional uniaxial tensile bioreactors used in current literature.Advanced roboticplatforms such as musculoskeletal humanoid robots and soft robotic actuators are promising technologies which may helpaddress translational gaps in tendon tissue engineering We suggest the proposed benets of these technologies and identifyrecent studies which have worked to implement these technologies in tssue engineering.Lastly,key chalenges to addressinadapting these robotic technologies and proposed future research directions for tendon tssue engineering are discussed.展开更多
We are pleased to devote the following two issues of Biomaterials Translational to the important subject of the potential translation of stem cells for regenerative medicine and disease treatment.Stem cells with capac...We are pleased to devote the following two issues of Biomaterials Translational to the important subject of the potential translation of stem cells for regenerative medicine and disease treatment.Stem cells with capacities to renew their own tissue are now considered present in all tissues and organs of the body.Such cells have been of great interest to biologists and clinicians over the past century,since Haeckel in his‘Natural history of creation’first coined the term in 1868.1 The nature of the definition of what constitutes a stem cell has changed with time,but since the 1970s there has been an explosion of research publications on stem cells(Figure 1).This has involved increasing consideration of these primitive cells,that exist in the embryo and postnatally,for translation to the clinic for medical use and significant public health benefit.The trend in research output continues to increase exponentially with almost 72,000 publications on stem cells being recorded in the past year alone(searched using Web of Science databases).Hence there is great urgency and adequate justification for dedication of appreciable journal emphasis to this topic.In this issue,Stem Cells-Part I,there are a variety of topics within this theme that are covered either as viewpoint,review or research papers.展开更多
基金supported in part by Fox and Necrosis funds from the Department of Orthopedic Surgery。
文摘PPeritendinous adhesion formation(PAF)can substantially limit the range of motion of digits.However,the origin of myofibroblasts in PAF tissues is still unclear.In this study,we found that the concentration of active TGF-β1 and the numbers of macrophages,mesenchymal stromal cells(MSCs),and myofibroblasts in human and mouse adhesion tissues were increased.Furthermore,knockout of TGF-β1 in macrophages or TGF-β1R2 in MSCs inhibited PAF by reducing MSC and myofibroblast infiltration and collagenⅠandⅢdeposition,respectively.Moreover,we found that MSCs differentiated into myofibroblasts to form adhesion tissues.Systemic injection of the TGF-β–neutralizing antibody 1D11 during the granulation formation stage of PAF significantly reduced the infiltration of MSCs and myofibroblasts and,subsequently,PAF.These results suggest that macrophage-derived TGF-β1 recruits MSCs to form myofibroblasts in peritendinous adhesions.An improved understanding of PAF mechanisms could help identify a potential therapeutic strategy.
基金JWL was supported by a MRC-Versus Arthritis Centre for Musculoskeletal Ageing Research PhD studentship(MR/R502364/1)AJN was supported by an Arthritis Research UK Career Development Fellowship(21743).
文摘Adiponectin is the most abundant circulating adipokine and is primarily involved in glucose metabolism and insulin resistance.Within the bone,osteoblasts and osteoclasts express the adiponectin receptors,however,there are conflicting reports on the effects of adiponectin on bone formation and turnover.Many studies have shown a pro-osteogenic role for adiponectin in in vivo murine models and in vitro:with increased osteoblast differentiation and activity,alongside lower levels of osteoclastogenesis.However,human studies often demonstrate an inverse relationship between adiponectin concentration and bone activity.Moreover,the presence of multiple isoforms of adiponectin and multiple receptor subtypes has the potential to lead to more complex signalling and functional consequences.As such,we still do not fully understand the importance of the adiponectin signalling pathway in regulating bone homeostasis and repair in health,with age and in disease.In this review,we explore our current understanding of adiponectin bioactivity in the bone;the significance of its different isoforms;and how adiponectin biology is altered in disease.Ultimately,furthering our understanding of adiponectin regulation of bone biology is key to developing pharmacological and non-pharmacological(lifestyle)interventions that target adiponectin signalling to boost bone growth and repair in healthy ageing,following injury or in disease.
基金financial support from Orthopaedic Research UK (P 470)Arthritis Research UK (grant 20299 and Oxford EOTC)
文摘The effects of vitamin D on osteoblast mineralization are well documented. Reports of the effects of vitamin D on osteoclasts, however, are conflicting, showing both inhibition and stimulation. Finding that resorbing osteoclasts in human bone express vitamin D receptor (VDR), we examined their response to different concentrations of 25-hydroxy vitamin D3 [25(OH)D3] (100 or 500 nmol·L^-1) and 1,25-dihydroxy vitamin D3 [1,25(OH)2D3] (0.1 or 0.5 nmol·L^-1) metabolites in cell cultures. Specifically, CD14+ monocytes were cultured in charcoal-stripped serum in the presence of receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Tartrate-resistant acid phosphatase (TRAP) histochemical staining assays and dentine resorption analysis were used to identify the size and number of osteoclast cells, number of nuclei per cell and resorption activity. The expression of VDR was detected in human bone tissue (ex vivo) by immunohistochemistry and in vitro cell cultures by western blotting. Quantitative reverse transcription-PCR (qRT-PCR) was used to determine the level of expression of vitamin D-related genes in response to vitamin D metabolites. VDR-related genes during osteoclastogenesis, shown by qRT-PCR, was stimulated in response to 500 nmol·L^-1 of 25(OH)D3 and 0.1-0.5 nmol·L^-1 of 1,25(OH)2D3, upregulating cytochrome P450 family 27 subfamily B member I (CYP27B1) and cytochrome P450 family 24 subfamily A member I (CYP24A1). Osteoclast fusion transcripts transmembrane 7 subfamily member 4 (tm7sf4) and nuclear factor of activated T-cell cytoplasmic 1 (nfatcl) where downregulated in response to vitamin D metabolites. Osteoclast number and resorption activity were also increased. Both 25(OH)D3 and 1,25(OH)2D3 reduced osteoclast size and number when co-treated with RANKL and M-CSF. The evidence for VDR expression in resorbing osteoclasts in vivo and low-dose effects of 1,25(OH)2D3 on osteoclasts in vitro may therefore provide insight into the effects of clinical vitamin D treatments, further providing a counterpoint to the high-dose effects reported from in vitro experiments.
基金the Graduate Student's Research and Innovation Fund of Sichuan University,No.2018YJSY108the China Postdoctoral Science Foundation Funded Project,No.2018M640931+1 种基金the Science and Technology Key Research and Development Program of Sichuan Province,No.2019YFS0142the National Natural Science Foundation of China,No.81901060.
文摘BACKGROUND The conventional implant approach involves flap elevation,which may result in increased soft tissue and bone loss and postoperative morbidity.The flapless surgical technique,aided by three-dimensional medical imaging equipment,is regarded as a possible alternative to the conventional approach to alleviate the above issues.Several studies have been performed regarding the role of flapless implant surgery.However,the results are inconsistent and there is no robust synthesis of long-term evidence to better inform surgeons regarding which type of surgical technique is more beneficial to the long-term prognosis of patients in need of implant insertion.AIM To compare the long-term clinical performance after flapless implant surgery to that after the conventional approach with flap elevation.METHODS PubMed,EMBASE,Cochrane Central Register of Controlled Trials,and grey literature databases were searched from inception to 23 September 2019.Randomised controlled trials(RCTs)and cohort studies comparing the long-term clinical performance after flapless implant surgery to that after the conventional approach over a follow-up of three years or more were included.Meta-analyses were conducted to estimate the odds ratios(ORs)or mean differences(MDs)and their 95%confidence intervals(CIs)between the long-term implant survival rate,marginal bone loss,and complication rate of the flapless and conventional groups.Subgroup analyses were carried out to account for the possible effects of the guided or free-hand method during flapless surgery.RESULTS Ten articles,including four RCTs and six cohort studies,satisfied the eligibility criteria and nine of them were included in the meta-analysis.There was no significant difference between the long-term implant survival rate[OR=1.30,95%CI(0.37,4.54),P=0.68],marginal bone loss[MD=0.01,95%CI(-0.42,0.44),P=0.97],and complication rate[OR=1.44,95%CI(0.77,2.68),P=0.25]after flapless implant surgery and the conventional approach.Moreover,subgroup analyses revealed that there was no statistically significant difference between the implant survival rate[guided:OR=1.52,95%CI(0.19,12.35),P=0.70];free-hand:n=1,could not be estimated,marginal bone loss[guided:MD=0.22,95%CI(-0.14,0.59),P=0.23;free-hand:MD=-0.27,95%CI(-1.10,0.57),P=0.53],or complication rate[guided:OR=1.16,95%CI(0.52,2.63),P=0.71;free-hand:OR=1.75,95%CI(0.66,4.63),P=0.26]in the flapless and conventional groups either with use of the surgical guide or by the free-hand method.CONCLUSION The flapless surgery and conventional approach had comparable clinical performance over three years or more.The guided or free-hand technique does not significantly affect the long-term outcomes of flapless surgery.
文摘Glucocorticoids remain the cornerstone of medicaltherapy in giant cell arteritis(GCA) and should be started immediately to prevent severe consequences of the disease, such as blindness. However, glucocorticoid therapy leads to significant toxicity in over 80% of the patients. Various steroid-sparing agents have been tried, but robust scientific evidence of their efficacy and safety is still lacking. Tocilizumab, a monoclonal IL-6 receptor blocker, has shown promising results in a number of case series and is now being tested in a multi-centre randomized controlled trial. Other targeted treatments, such as the use of abatacept, are also now under investigation in GCA. The need for surgical treatment is rare and should ideally be performed in a quiescent phase of the disease. Not all patients follow the same course, but there are no valid biomarkers to assess therapy response. Monitoring of disease progress still relies on assessing clinical features and measuring inflammatory markers(C-reactive protein and erythrocyte sedimentation rate). Imaging techniques(e.g., ultrasound) are clearly important screening tools for aortic aneurysms and assessing patients with largevessel involvement, but may also have an important role as biomarkers of disease activity over time or in response to therapy. Although GCA is the most common form of primary vasculitis, the optimal strategies for treatment and monitoring remain uncertain.
文摘“It is the responsibility of everyone involved to ensure that the published record is an unbiased,accurate representation of research”[1].The research record is often manipulated for short term gain but at the risk of harm to patients.The medical research community needs to implement changes to ensure that readers obtain the truth about all research,especially reports of randomised trials,which hold a special place in answering what works best for patients.
文摘In all aspects of communication the meanings of words and definitions are of paramount importance for clear understanding and transmission of ideas.However,these meanings may change with time so that words and phrases take on different interpretations.Furthermore,the way words are used in writing significantly affects the conveyance of ideas from one mind to another.1 In the long history of the study of the histogenesis of bone we see some of these changes in meaning and understanding of concepts that have perhaps contributed to serious misinterpretation of the ideas of some investigators in the field.It is hoped that this brief historical perspective may explain and clarify at least some of the problems that have resulted.
文摘Despite being over thirty years since there was proof that the hypothetical osteogenic stem cell existed,1 demonstration of any dramatic value for the use of such cells in orthopaedic clinical practice by tissue engineering approaches has not yet been realised.This is notwithstanding extensive studies concerning the likely nature and potentials of these cells in countless in vitro and in vivo investigations.In part,this is based on the confusion caused by exaggeration of claims by unreliable,or at best naïve,investigators and opportunistic entrepreneurs who have grossly misinterpreted data from many ill-conceived studies.2,3 This pseudo-science has been harmful,especially to the stem cell field,both academically and commercially.
文摘For successful translational use of stem cells in biomedicine,knowledge of the quality of the cells,the presence of bioactive factors,and the nature of the microenvironmental niches is paramount.They may be regarded as the Three Musketeers as they unite“All for one,one for all”1 to control the trafficking,survival,proliferation,and differentiation of stem cells.In this second themed issue of Biomaterials Translational,entitled“Application of Stem Cells in Translational Medicine:Stem Cells Part II”.
基金Work in S.P.'s laboratory is supported by a Cancer Research UK Career Development Fellowship,Grant ID C59392/A25064Royal Society,UKand The Clarendon Fund and St Edmund Hall Scholarship,UK,SFF1920_CB_MSD_759707.
文摘Dedifferentiation of cell identity to a progenitor-like or stem cell-like state with increased cellular plasticity is frequently observed in cancer formation.During this process,a subpopulation of cells in tumours acquires a stem cell-like state partially resembling to naturally occurring pluripotent stem cells that are temporarily present during early embryogenesis.Such characteristics allow these cancer stem cells(CSCs)to give rise to the whole tumour with its entire cellular heterogeneity and thereby support metastases formation while being resistant to current cancer therapeutics.Cancer development and progression are demarcated by transcriptional dysregulation.In this article,we explore the epigenetic mechanisms shaping gene expression during tumorigenesis and cancer stem cell formation,with an emphasis on 3D chromatin architecture.Comparing the pluripotent stem cell state and epigenetic reprogramming to dedifferentiation in cellular transformation provides intriguing insight to chromatin dynamics.We suggest that the 3D chromatin architecture could be used as a target for re-sensitizing cancer stem cells to therapeutics.
基金support of the United Kingdom's Engineering and Physical Sciences Research Council(project number:P/S003509/1)and the Rhodes Trust.
文摘Tendon disease is a significant and growing burden to healthcare systems.One strategy to address this challenge is tssueengineering.A widely held view in this feld is that mechanical stimulation provided to constructs should replicate themechanicaienvironment of native tissue as closely as possible.We review recent tendon tissue engineering studies inthisarticle and highlight limitations of conventional uniaxial tensile bioreactors used in current literature.Advanced roboticplatforms such as musculoskeletal humanoid robots and soft robotic actuators are promising technologies which may helpaddress translational gaps in tendon tissue engineering We suggest the proposed benets of these technologies and identifyrecent studies which have worked to implement these technologies in tssue engineering.Lastly,key chalenges to addressinadapting these robotic technologies and proposed future research directions for tendon tssue engineering are discussed.
文摘We are pleased to devote the following two issues of Biomaterials Translational to the important subject of the potential translation of stem cells for regenerative medicine and disease treatment.Stem cells with capacities to renew their own tissue are now considered present in all tissues and organs of the body.Such cells have been of great interest to biologists and clinicians over the past century,since Haeckel in his‘Natural history of creation’first coined the term in 1868.1 The nature of the definition of what constitutes a stem cell has changed with time,but since the 1970s there has been an explosion of research publications on stem cells(Figure 1).This has involved increasing consideration of these primitive cells,that exist in the embryo and postnatally,for translation to the clinic for medical use and significant public health benefit.The trend in research output continues to increase exponentially with almost 72,000 publications on stem cells being recorded in the past year alone(searched using Web of Science databases).Hence there is great urgency and adequate justification for dedication of appreciable journal emphasis to this topic.In this issue,Stem Cells-Part I,there are a variety of topics within this theme that are covered either as viewpoint,review or research papers.