Mesenchymal stem cells(MSCs)closely interact with the immune system,and they are known to secrete inflammatory cytokines in response to stress stimuli.The biological function of MSC-derived inflammatory cytokines rema...Mesenchymal stem cells(MSCs)closely interact with the immune system,and they are known to secrete inflammatory cytokines in response to stress stimuli.The biological function of MSC-derived inflammatory cytokines remains elusive.Here,we reveal that even under physiological conditions,MSCs produce and release a low level of tumor necrosis factor alpha(TNFα),which is unexpectedly required for preserving the self-renewal and differentiation of MSCs via autocrine/paracrine signaling.Furthermore,TNFαcritically maintains MSC function in vivo during bone homeostasis.Mechanistically,we unexpectedly discovered that physiological levels of TNFαsafeguard MSC homeostasis in a receptor-independent manner through mechanical force-driven endocytosis and that endocytosed TNFαbinds to mammalian target of rapamycin(mTOR)complex 2 and restricts mTOR signaling.Importantly,inhibition of mTOR signaling by rapamycin serves as an effective osteoanabolic therapeutic strategy to protect against TNFαdeficiency and mechanical unloading.Collectively,these findings unravel the physiological framework of the dynamic TNFαshuttlebased mTOR equilibrium that governs MSC and bone homeostasis.展开更多
The development of cell biology, molecular biology, and material science, has been propelling biomimic tissue-engineered skins to become more sophisticated in scientificity and more simplified in practicality. In orde...The development of cell biology, molecular biology, and material science, has been propelling biomimic tissue-engineered skins to become more sophisticated in scientificity and more simplified in practicality. In order to improve the safety, durability, elasticity, biocompatibility, and clinical efficacy of tissue-engineered skin, several powerful seed cells have already found their application in wound repair, and a variety of bioactive scaffolds have been discovered to influence cell fate in epidermogenesis. These exuberant interests provide insights into advanced construction strategies for complex skin mimics. Based on these exciting developments, a complete full-thickness tissue-engineered skin is likely to be generated.展开更多
Aim To characterize the odontogenic capability of apical bud and phenotypical change of apical bud cells （ABCs） in different microenvironment.Methodology Incisor apical bud tissues from neonatal SD rat were dissecte...Aim To characterize the odontogenic capability of apical bud and phenotypical change of apical bud cells （ABCs） in different microenvironment.Methodology Incisor apical bud tissues from neonatal SD rat were dissected and transplanted into the renal capsules to determine their odontogenic capability. Meanwhile ABCs were cultured and purified by repeated differential trypsinization. Then ABCs were cultured with conditioned medium from developing apical complex cells （DAC-CM）. Immunocytochemistry, reverse transcriptase polymerase chain reaction （RT-PCR） and scanning electron microscope （SEM） were performed to compare the biolo- gical change of ABC treated with or without DAC-CM. Results First we confirmed the ability of apical bud to form crown-like structure ectopically. Equally important, by using the developing apical complex （DAC） condi- tioned medium, we found the microenvironment created by root could abrogate the ＂crown＂ features of ABCs and promote their proliferation and differentiation. Conclusion ABCs possess odontogenic capability to form crown-like tissues and this property can be affected by root-produced microenvironment.展开更多
In recent years, rapid development of tissue engineering technology provides possibilities for the construction of artificial tissues or organs. In construction of engineered kidneys, researchers used native decellula...In recent years, rapid development of tissue engineering technology provides possibilities for the construction of artificial tissues or organs. In construction of engineered kidneys, researchers used native decellularized extracellular matrix(ECM) as the scaffolds to recellularization. However, thrombosis has been a great issue that hinders the progress of transplantation in vivo. In this study, heparin was immobilized to the collagen part of decellularized scaffold with collagen-binding peptide(CBP). Through the anticoagulant and endothelial cell reperfusion experiments, it can be demonstrated that the heparinized scaffolds absorbed less platelets and red blood cells which can effectively reduce the formation of thrombosis. Moreover, it is conducive to longterm adhesion of endothelial cells which is important for the formation of subsequent vascularization. Taken together, our results reveal that the whole kidney can be modified by CBP-heparin composite to reduce the thrombosis and provide the better conditions for neovascularization.展开更多
Background: Several patients experience persistent otorrhea after a flawless surgical procedure because of insufficient epithelial healing. Several efforts, such as autologous tissue allograft and xenograft, have been...Background: Several patients experience persistent otorrhea after a flawless surgical procedure because of insufficient epithelial healing. Several efforts, such as autologous tissue allograft and xenograft, have been made to halt otorrhea. However, a stable technology to induce temporal epithelial repair is yet to be established. Therefore, this study aims to investigate whether implantation of seeding adipose-derived mesenchymal stem cell (ADMSC) aggregates on extracellular matrix (ECM;herein, ADMSC aggregate-ECM) into damaged skin wound promotes skin regeneration. Methods: ADMSC aggregate-ECM was prepared using a previously described procedure that isolated ADMSCs from rabbits and applied to the auricle and auditory meatus wound beds of New Zealand white rabbits. Wound healing was assessed by general observation and hematoxylin and eosin (H&E) staining. Secretion of growth factor of the tissue was evaluated by western blotting. Two other groups, namely, ECM and control, were used. Comparisons of three groups were conducted by one-way analysis of variance analysis. Results: ADMSCs adhered tightly to the ECM and quickly formed cell sheets. At 2 weeks, general observation and H&E staining indicated that the wound healing rates in the ADMSC aggregate-ECM (69.02±6.36%) and ECM (59.32 + 4.10%) groups were higher than that in the control group (43.74± 12.15%;P=0.005, P<0.001, respectively) in ear auricle excisional wounds. At 7 weeks, The scar elevation index was evidently reduced in the ADMSC aggregate-ECM (2.08±0.87) and ECM (2.31 ±0.33) groups compared with the control group (4.06 ±0.45;P < 0.001, P < 0.001, respectively). In addition, the scar elevation index of the ADMSC aggregate-ECM group reached the lowest rate 4 weeks in advance. In auditory meatus excisional wounds, the ADMSC aggregate-ECM group had the largest range of normal skin-like structure at 4 weeks. The ADMSC aggregate-ECM and ECM groups secreted increased amounts of growth factors that contributed to skin regeneration at weeks 1 and 2, respectively. Conclusions: ADMSC aggregate-ECM and ECM are effective repair materials for wound healing, especially ADMSC aggregate- ECM. This approach will provide a meaningful experimental basis for mastoid epithelium repair in subsequent clinical trials.展开更多
基金This work was supported by grants from the National Institute of Dental and Craniofacial Research,National Institutes of Health,Department of Health and Human Services(K99E025915 to C.C.)a Schoenleber Pilot Research Grant(to S.S.)from the University of Pennsylvania School of Dental Medicine,the Guangdong Financial Fund for High-Caliber Hospital Construction,the Postdoctoral Innovative Talents Support Program of China(BX20190380 to B.S.)the General Program of the China Postdoctoral Science Foundation(2019M663986 to B.S.).
文摘Mesenchymal stem cells(MSCs)closely interact with the immune system,and they are known to secrete inflammatory cytokines in response to stress stimuli.The biological function of MSC-derived inflammatory cytokines remains elusive.Here,we reveal that even under physiological conditions,MSCs produce and release a low level of tumor necrosis factor alpha(TNFα),which is unexpectedly required for preserving the self-renewal and differentiation of MSCs via autocrine/paracrine signaling.Furthermore,TNFαcritically maintains MSC function in vivo during bone homeostasis.Mechanistically,we unexpectedly discovered that physiological levels of TNFαsafeguard MSC homeostasis in a receptor-independent manner through mechanical force-driven endocytosis and that endocytosed TNFαbinds to mammalian target of rapamycin(mTOR)complex 2 and restricts mTOR signaling.Importantly,inhibition of mTOR signaling by rapamycin serves as an effective osteoanabolic therapeutic strategy to protect against TNFαdeficiency and mechanical unloading.Collectively,these findings unravel the physiological framework of the dynamic TNFαshuttlebased mTOR equilibrium that governs MSC and bone homeostasis.
基金a grant from National High Technology Research and Development Program of China (863 Program) (2012AA020507)
文摘The development of cell biology, molecular biology, and material science, has been propelling biomimic tissue-engineered skins to become more sophisticated in scientificity and more simplified in practicality. In order to improve the safety, durability, elasticity, biocompatibility, and clinical efficacy of tissue-engineered skin, several powerful seed cells have already found their application in wound repair, and a variety of bioactive scaffolds have been discovered to influence cell fate in epidermogenesis. These exuberant interests provide insights into advanced construction strategies for complex skin mimics. Based on these exciting developments, a complete full-thickness tissue-engineered skin is likely to be generated.
基金supported by National Nature Science Foundation of China(Project No.3057 2046,30725042)
文摘Aim To characterize the odontogenic capability of apical bud and phenotypical change of apical bud cells （ABCs） in different microenvironment.Methodology Incisor apical bud tissues from neonatal SD rat were dissected and transplanted into the renal capsules to determine their odontogenic capability. Meanwhile ABCs were cultured and purified by repeated differential trypsinization. Then ABCs were cultured with conditioned medium from developing apical complex cells （DAC-CM）. Immunocytochemistry, reverse transcriptase polymerase chain reaction （RT-PCR） and scanning electron microscope （SEM） were performed to compare the biolo- gical change of ABC treated with or without DAC-CM. Results First we confirmed the ability of apical bud to form crown-like structure ectopically. Equally important, by using the developing apical complex （DAC） condi- tioned medium, we found the microenvironment created by root could abrogate the ＂crown＂ features of ABCs and promote their proliferation and differentiation. Conclusion ABCs possess odontogenic capability to form crown-like tissues and this property can be affected by root-produced microenvironment.
基金supported by grants from the National Key Research and Development Program of China (2016YFC1101400, 2016YFC1102903)the National Natural Science Foundation of China (31670995, 81470679)
文摘In recent years, rapid development of tissue engineering technology provides possibilities for the construction of artificial tissues or organs. In construction of engineered kidneys, researchers used native decellularized extracellular matrix(ECM) as the scaffolds to recellularization. However, thrombosis has been a great issue that hinders the progress of transplantation in vivo. In this study, heparin was immobilized to the collagen part of decellularized scaffold with collagen-binding peptide(CBP). Through the anticoagulant and endothelial cell reperfusion experiments, it can be demonstrated that the heparinized scaffolds absorbed less platelets and red blood cells which can effectively reduce the formation of thrombosis. Moreover, it is conducive to longterm adhesion of endothelial cells which is important for the formation of subsequent vascularization. Taken together, our results reveal that the whole kidney can be modified by CBP-heparin composite to reduce the thrombosis and provide the better conditions for neovascularization.
基金a grant from the National Natural Science Foundation of China (No. 81170904).
文摘Background: Several patients experience persistent otorrhea after a flawless surgical procedure because of insufficient epithelial healing. Several efforts, such as autologous tissue allograft and xenograft, have been made to halt otorrhea. However, a stable technology to induce temporal epithelial repair is yet to be established. Therefore, this study aims to investigate whether implantation of seeding adipose-derived mesenchymal stem cell (ADMSC) aggregates on extracellular matrix (ECM;herein, ADMSC aggregate-ECM) into damaged skin wound promotes skin regeneration. Methods: ADMSC aggregate-ECM was prepared using a previously described procedure that isolated ADMSCs from rabbits and applied to the auricle and auditory meatus wound beds of New Zealand white rabbits. Wound healing was assessed by general observation and hematoxylin and eosin (H&E) staining. Secretion of growth factor of the tissue was evaluated by western blotting. Two other groups, namely, ECM and control, were used. Comparisons of three groups were conducted by one-way analysis of variance analysis. Results: ADMSCs adhered tightly to the ECM and quickly formed cell sheets. At 2 weeks, general observation and H&E staining indicated that the wound healing rates in the ADMSC aggregate-ECM (69.02±6.36%) and ECM (59.32 + 4.10%) groups were higher than that in the control group (43.74± 12.15%;P=0.005, P<0.001, respectively) in ear auricle excisional wounds. At 7 weeks, The scar elevation index was evidently reduced in the ADMSC aggregate-ECM (2.08±0.87) and ECM (2.31 ±0.33) groups compared with the control group (4.06 ±0.45;P < 0.001, P < 0.001, respectively). In addition, the scar elevation index of the ADMSC aggregate-ECM group reached the lowest rate 4 weeks in advance. In auditory meatus excisional wounds, the ADMSC aggregate-ECM group had the largest range of normal skin-like structure at 4 weeks. The ADMSC aggregate-ECM and ECM groups secreted increased amounts of growth factors that contributed to skin regeneration at weeks 1 and 2, respectively. Conclusions: ADMSC aggregate-ECM and ECM are effective repair materials for wound healing, especially ADMSC aggregate- ECM. This approach will provide a meaningful experimental basis for mastoid epithelium repair in subsequent clinical trials.
