Background:Eccrine sweat gland(SG)plays a crucial role in thermoregulation but exhibits very limited regenerative potential.Although SG lineage-restricted niches dominate SG morphogenesis and benefit SG regeneration,r...Background:Eccrine sweat gland(SG)plays a crucial role in thermoregulation but exhibits very limited regenerative potential.Although SG lineage-restricted niches dominate SG morphogenesis and benefit SG regeneration,rebuilding niches in vivo is challenging for stem cell therapeutic applications.Hence,we attempted to screen and tune the critical niche-responding genes that dually respond to both biochemical and structural cues,which might be a promising strategy for SG regeneration.Methods:An artificial SG lineage-restricted niche consisting of mouse plantar dermis homogenates(i.e.biochemical cues)and 3D architecture(i.e.structural cues)was built in vitro by using an extrusion-based 3D bioprinting approach.Mouse bone marrow-derived mesenchymal stem cells(MSCs)were then differentiated into the induced SG cells in the artificial SG lineage-restricted niche.To decouple biochemical cues from structural cues,the transcriptional changes aroused by pure biochemical cues,pure structural cues and synergistic effects of both cues were analyzed pairwise,respectively.Notably,only niche-dual-responding genes that are differentially expressed in response to both biochemical and structural cues and participate in switching MSC fates towards SG lineage were screened out.Validations in vitro and in vivo were respectively conducted by inhibiting or activating the candidate niche-dual-responding gene(s)to explore the consequent effects on SG differentiation.Results:Notch4 is one of the niche-dual-responding genes that enhanced MSC stemness and pro-moted SG differentiation in 3D-printed matrix in vitro.Furthermore,inhibiting Notch4 specifically reduced keratin 19-positive epidermal stem cells and keratin 14-positive SG progenitor cells,thus further delaying embryonic SG morphogenesis in vivo.Conclusions:Notch4 not only participates in mouse MSC-induced SG differentiation in vitro but is also implicated in mouse eccrine SG morphogenesis in vivo.展开更多
Spinal cord injury(SCI)leads to nerve cell apoptosis and loss of motor function.Herein,excessive activation of the M1 phenotype macrophages/microglia is found to be the main reason for the poor prognosis of SCI,but th...Spinal cord injury(SCI)leads to nerve cell apoptosis and loss of motor function.Herein,excessive activation of the M1 phenotype macrophages/microglia is found to be the main reason for the poor prognosis of SCI,but the selective activation phenotype(M2)macrophages/microglia facilitates the recovery of SCI.Thereafter,we used gold nanoclusters loaded berberine(BRB-AuNCs)to reduce inflammation by inhibiting the activation of M1 phenotype macrophages/microglia,which simultaneously inhibited neuronal apoptosis after SCI.In vitro and in vivo experiments showed that BRB-AuNCs reduced M1 protein marker CD86,increased M2 protein marker CD206,reduced inflammation and apoptotic cytokines(IL-1β,IL-6,TNF-α,Cleaved Caspase-3 and Bax).These results indicate that BRB-AuNCs have excellent anti-inflammatory and anti-apoptotic effects by inducing the polarization of macrophages/microglia from M1 phenotype to M2 phenotype.Thereafter,the motor functions of SCI rats were significantly improved after treatment with BRB-AuNCs.This work not only provides a new way for the treatment of SCI but also broadens BRB utilization strategies.展开更多
On account of the poor biocompatibility of synthetic prosthesis,millions of rhinoplasty recipients have been forced to choose autologous costal cartilage as grafts,which suffer from limited availability,morbidity at t...On account of the poor biocompatibility of synthetic prosthesis,millions of rhinoplasty recipients have been forced to choose autologous costal cartilage as grafts,which suffer from limited availability,morbidity at the donor site and prolonged operation time.Here,as a promising alternative to autologous costal cartilage,we developed a novel xenogeneic costal cartilage and explored its feasibility as a rhinoplasty graft for the first time.Adopting an improved decellularization protocol,in which the ionic detergent was substituted by trypsin,the resulting decellularized graft was confirmed to preserve more structural components and better mechanics,and eliminate cellular components effectively.The in vitro and in vivo compatibility experiments demonstrated that the decellularized graft showed excellent biocompatibility and biosecurity.Additionally,the functionality assessment of rhinoplasty was performed in a rabbit model,and the condition of grafts after implantation was comprehensively evaluated.The optimized graft exhibited better capacity to reduce the degradation rate and maintain the morphology,in comparison to the decellularized costal cartilage prepared by conventional protocol.These findings indicate that this optimized graft derived from decellularized xenogeneic costal cartilage provides a new prospective for future investigations of rhinoplasty prosthesis and has great potential for clinical application.展开更多
基金supported by the NationalNature Science Foundation of China(82002056,32000969,92268206)The general funding grants(2020 M673672)+5 种基金the special funding grants(in-station,2022 T150789)the China Postdoctoral Science Foundation,theMilitaryMedical Research Projects(145AKJ260015000X,2022-JCJQ-ZD-096-00)National key research and development program(2022YFA1104604)Key Support Program for Growth Factor Research(SZYZ-TR-03)the Science Fund for National Defense Distinguished Young Scholars(2022-JCJQ-ZQ-016)Youth Independent Innovation Science Fund Project of PLA General Hospital(22QNFC018).
文摘Background:Eccrine sweat gland(SG)plays a crucial role in thermoregulation but exhibits very limited regenerative potential.Although SG lineage-restricted niches dominate SG morphogenesis and benefit SG regeneration,rebuilding niches in vivo is challenging for stem cell therapeutic applications.Hence,we attempted to screen and tune the critical niche-responding genes that dually respond to both biochemical and structural cues,which might be a promising strategy for SG regeneration.Methods:An artificial SG lineage-restricted niche consisting of mouse plantar dermis homogenates(i.e.biochemical cues)and 3D architecture(i.e.structural cues)was built in vitro by using an extrusion-based 3D bioprinting approach.Mouse bone marrow-derived mesenchymal stem cells(MSCs)were then differentiated into the induced SG cells in the artificial SG lineage-restricted niche.To decouple biochemical cues from structural cues,the transcriptional changes aroused by pure biochemical cues,pure structural cues and synergistic effects of both cues were analyzed pairwise,respectively.Notably,only niche-dual-responding genes that are differentially expressed in response to both biochemical and structural cues and participate in switching MSC fates towards SG lineage were screened out.Validations in vitro and in vivo were respectively conducted by inhibiting or activating the candidate niche-dual-responding gene(s)to explore the consequent effects on SG differentiation.Results:Notch4 is one of the niche-dual-responding genes that enhanced MSC stemness and pro-moted SG differentiation in 3D-printed matrix in vitro.Furthermore,inhibiting Notch4 specifically reduced keratin 19-positive epidermal stem cells and keratin 14-positive SG progenitor cells,thus further delaying embryonic SG morphogenesis in vivo.Conclusions:Notch4 not only participates in mouse MSC-induced SG differentiation in vitro but is also implicated in mouse eccrine SG morphogenesis in vivo.
基金supported by the National Natural Science Foundation of China(NSFC)(NO.81871556,82072165)Liaoning Revitalization Talents Program(NO.XLYC1902108).
文摘Spinal cord injury(SCI)leads to nerve cell apoptosis and loss of motor function.Herein,excessive activation of the M1 phenotype macrophages/microglia is found to be the main reason for the poor prognosis of SCI,but the selective activation phenotype(M2)macrophages/microglia facilitates the recovery of SCI.Thereafter,we used gold nanoclusters loaded berberine(BRB-AuNCs)to reduce inflammation by inhibiting the activation of M1 phenotype macrophages/microglia,which simultaneously inhibited neuronal apoptosis after SCI.In vitro and in vivo experiments showed that BRB-AuNCs reduced M1 protein marker CD86,increased M2 protein marker CD206,reduced inflammation and apoptotic cytokines(IL-1β,IL-6,TNF-α,Cleaved Caspase-3 and Bax).These results indicate that BRB-AuNCs have excellent anti-inflammatory and anti-apoptotic effects by inducing the polarization of macrophages/microglia from M1 phenotype to M2 phenotype.Thereafter,the motor functions of SCI rats were significantly improved after treatment with BRB-AuNCs.This work not only provides a new way for the treatment of SCI but also broadens BRB utilization strategies.
基金supported by Sichuan Science and Technology Program(2020YFH0008)National Natural Science Foundation of China(No.81771351)+1 种基金Joint Research Fund Liaoning-Shenyang National Laboratory for Materials Science(2019JH3/30100022)National Key R&D Program of China(2017YFA0105802).
文摘On account of the poor biocompatibility of synthetic prosthesis,millions of rhinoplasty recipients have been forced to choose autologous costal cartilage as grafts,which suffer from limited availability,morbidity at the donor site and prolonged operation time.Here,as a promising alternative to autologous costal cartilage,we developed a novel xenogeneic costal cartilage and explored its feasibility as a rhinoplasty graft for the first time.Adopting an improved decellularization protocol,in which the ionic detergent was substituted by trypsin,the resulting decellularized graft was confirmed to preserve more structural components and better mechanics,and eliminate cellular components effectively.The in vitro and in vivo compatibility experiments demonstrated that the decellularized graft showed excellent biocompatibility and biosecurity.Additionally,the functionality assessment of rhinoplasty was performed in a rabbit model,and the condition of grafts after implantation was comprehensively evaluated.The optimized graft exhibited better capacity to reduce the degradation rate and maintain the morphology,in comparison to the decellularized costal cartilage prepared by conventional protocol.These findings indicate that this optimized graft derived from decellularized xenogeneic costal cartilage provides a new prospective for future investigations of rhinoplasty prosthesis and has great potential for clinical application.
