BACKGROUND Recently,stem cell therapy has been extensively studied as a promising treatment for decompensated liver cirrhosis(DLC).Technological advances in endoscopic ultrasonography(EUS)have facilitated EUS-guided p...BACKGROUND Recently,stem cell therapy has been extensively studied as a promising treatment for decompensated liver cirrhosis(DLC).Technological advances in endoscopic ultrasonography(EUS)have facilitated EUS-guided portal vein(PV)access,through which stem cells can be precisely infused.AIM To investigate the feasibility and safety of fresh autologous bone marrow injection into the PV under EUS guidance in patients with DLC.METHODS Five patients with DLC were enrolled in this study after they provided written informed consent.EUS-guided intraportal bone marrow injection with a 22G FNA needle was performed using a transgastric,transhepatic approach.Several parameters were assessed before and after the procedure for a follow-up period of 12 mo.RESULTS Four males and one female with a mean age of 51 years old participated in this study.All patients had hepatitis B virus-related DLC.EUS-guided intraportal bone marrow injection was performed in all patients successfully without any complications such as hemorrhage.The clinical outcomes of the patients revealed improvements in clinical symptoms,serum albumin,ascites,and Child-Pugh scores throughout the 12-mo follow-up.CONCLUSION The use of EUS-guided fine needle injection for intraportal delivery of bone marrow was feasible and safe and appeared effective in patients with DLC.This treatment may thus be a safe,effective,non-radioactive,and minimally invasive treatment for DLC.展开更多
Objective:To explore the effect and mechanism of Xuebijing injection (XBJ) on the hematopoietic homeostasis of bone marrow (BM) in septic mice. Methods:BM cells stimulated with XBJ were analyzed by inverted optical mi...Objective:To explore the effect and mechanism of Xuebijing injection (XBJ) on the hematopoietic homeostasis of bone marrow (BM) in septic mice. Methods:BM cells stimulated with XBJ were analyzed by inverted optical microscope and qPCR, to evaluate the effect of XBJ on differentiation function of BM cells in vitro. Lipopolysaccharide (LPS) 055:B5 at the dose of 20mg/kg was used to establish the sepsis model. To determine the hematopoietic stem cells homeostasis affected by LPS in mice, BM cells were isolated and analyzed by flow cytometry based on the immunophenotypic surface markers. 20ml/kg of XBJ was administered by tail vein once/day after peritoneal injection of LPS. All animals were sacrificed on the fifth day. The frequency of hematopoietic stem cells (HSC) and immune cells in mice were quantified by flow cytometry. The gene expression of transcription factors were detected by qPCR. Results:XBJ promoted myeloid differentiation of BM cells in vitro, which may be related to the mRNA expression of the transcription factors. The results in vivo showed the percentage of BM Lin-SCA-1+c-KIT+(LSK) cells, and Long-term HSCs (LT-HSC) were significantly increased in LPS group. But the percentage of multipotential progenitors (MPPs), granulocyte-monocyte progenitor (GMP) and megakaryocytic-erythroid precursor (MEP) were significantly decreased in LPS group. Whereas, XBJ improved the immune function in sepsis mice by suppression the LSK expansion in vivo. The result of qPCR showed that LSD1 and PU.1 mRNA expression in XBJ group were significantly higher than LPS group and control group respectively. Conclusion:Xuebijing injection can improve immune function in sepsis mice by regulating hematopoietic homeostasis. Its mechanism may be related to the up-regulation of LSD1 and PU.1 gene expressions.展开更多
Retinal degenerative diseases affecting the outer retina in its many forms(inherited,acquired or induced)are characterized by photoreceptor loss,and represent currently a leading cause of irreversible vision loss in t...Retinal degenerative diseases affecting the outer retina in its many forms(inherited,acquired or induced)are characterized by photoreceptor loss,and represent currently a leading cause of irreversible vision loss in the world.At present,there are very few treatments capable of preventing,recovering or reversing photoreceptor degeneration or the secondary retinal remodeling,which follows photoreceptor loss and can also cause the death of other retinal cells.Thus,these diseases are nowadays one of the greatest challenges in the field of ophthalmological research.Bone marrow derived-mononuclear stem cell transplantation has shown promising results for the treatment of photoreceptor degenerations.These cells may have the potential to slow down photoreceptor loss,and therefore should be applied in the early stages of photoreceptor degenerations.Furthermore,because of their possible paracrine effects,they may have a wide range of clinical applications,since they can potentially impact on several retinal cell types at once and photoreceptor degenerations can involve different cells and/or begin in one cell type and then affect adjacent cells.The intraocular injection of bone marrow derived-mononuclear stem cells also enhances the outcomes of other treatments aimed to protect photoreceptors.Therefore,it is likely that future investigations may combine bone marrow derived-mononuclear stem cell therapy with other systemic or intraocular treatments to obtain greater therapeutic effects in degenerative retinal diseases.展开更多
背景:医用水凝胶是具有三维结构网络的新型功能高分子材料,具有出色的生物相容性,目前已在组织工程领域、药物载体领域有广泛研究,但基于组织工程探究医用水凝胶与中医药结合治疗疾病的研究还处于初期探索阶段。因此,通过对医用水凝胶...背景:医用水凝胶是具有三维结构网络的新型功能高分子材料,具有出色的生物相容性,目前已在组织工程领域、药物载体领域有广泛研究,但基于组织工程探究医用水凝胶与中医药结合治疗疾病的研究还处于初期探索阶段。因此,通过对医用水凝胶机制作用的剖析,整合医用水凝胶与中医药在研究中联合应用的文章,进而更好地为科研工作者提供思路,对中医药与医用水凝胶联合应用具有重要意义。目的:基于组织工程研究探讨中医药联合医用水凝胶治疗疾病的策略及意义。方法:利用PubMed和中国知网数据库,检索有关中医药联合医用水凝胶在组织工程中应用的文献,检索时间为2010年1月至2022年11月,英文检索词为“hydrogel,traditional Chinese medicine,drug carrier,tissue engineering”,中文检索词为“医用水凝胶、中医药、药物载体、组织工程”。根据纳入与排除标准对所有文章进行初筛后,最终纳入61篇文章进行综述。结果与结论:①中医药联合医用水凝胶的应用虽然在关节内、组织器官内、软组织伤口和组织工程等方面有所涉及,但除了中医药结合水凝胶敷料在临床应用治疗软组织损伤外,其他方面尚处于基础实验阶段。②中医药联合医用水凝胶的发展有着巨大潜力和发展前景,但对于性能要求较高的凝胶在制造方面存在一定难度,理化性质精确掌握难度较大。③目前综合来看可注射水凝胶凭借着简便易用的特点,其在与中医药联合使用可延伸范围较广,可用于关节、器官和组织工程相关疾病的治疗;智能水凝胶有较高的灵敏度和可逆转化性也可满足特殊环境下的使用;将两者结合的中医药使用过程中还需要明确中药成分的作用机制。④中医药联合医用水凝胶治疗疾病的策略应着手于中医药对器官、组织、细胞的治疗作用联合适当种类的医用水凝胶进行匹配,可弥补传统中医给药方式和频繁给药的不足,在组织工程方面可以用水凝胶负载中药干预后的干细胞,或者同时负载中药和干细胞用于相关疾病的治疗。⑤在中医药联合医用水凝胶应用的未来研究中,还需要考虑:应当确保医用水凝胶生物性能可以量化,以不同材料不同制造工艺把握水凝胶特性,制造出所需要的符合应用条件的医用水凝胶;在中医药方面需要对已知中药单体、中药复方提取物的治疗效果和应用机制全面了解剖析,在更明了的机制下实现中医药与医用水凝胶更多更完美的结合;借助医学科技创新能力的不断提高,医用水凝胶可以创新性地结合中医药其他传统治疗方法比如针灸、推拿和拔罐等方式进行多角度运用。展开更多
Objective:To explore the mechanism of acupoint injection of bone marrow mesenchymal stem cells(BM-MSCs) in improving blood flow in the rat with hind limb ischemia.Methods:Twenty-four SD rats were randomly divided into...Objective:To explore the mechanism of acupoint injection of bone marrow mesenchymal stem cells(BM-MSCs) in improving blood flow in the rat with hind limb ischemia.Methods:Twenty-four SD rats were randomly divided into 4 groups:normal control group(n=6),model group(n=6),BM-MSCs acupoint injection group(AI group,n=6) and BM-MSC intramuscular injection group(MI group,n=6).Sanyinjiao(SP 6),Housanli(ST 36),Zhaohai(KI 6),Huantiao(GB 30) and Yanglingquan(GB 34) were selected for the AI group,and five non-acupoints were selected on gastrocnemius and adductor of ischemic hind limbs in the MI group.BM-MSCs were injected to the latter two groups.The rat hind limb ischemia model was established with the method of blocking the femoral artery and its branches.Three weeks after injection of BM-MSCs,in each group,hindlimb adductor and gastrocnemius were taken from the ischemic side.Expressions of vascular endothelial growth factor(VEGF) and transfer growth factor-β1(TGF-β1) in the skeletal muscle were determined with immunohistochemical method,and the small arteries in the skeletal muscle were labeled with α-SMA immunohistochemical staining method,the density of small arteries(number of arterioles /number of muscle fibers) and the number of the blood vessel with VEGF positive expression were calculated.The serum levels of VEGF and nitric oxide(NO) were detected.Results:Compared with the model group,the expression of VEGF and TGF-β1,and the density of small arteries and the number of VEGF-positive blood vessels in the AI group and the MI group significantly increased(both P<0.01).Compared with the MI group,the density of small arteries and the number of VEGF-positive blood vessels in the AI group significantly increased(both P<0.01);Compared with the model group and the normal control group,the serum expression quantity of NO and VEGF in the AI group and the MI group were significantly increased(P<0.01).Conclusions:Acuppoint injection of BM-MSCs secrets more VEGF,TGF-β1 and NO to increase angiogenesis and arteriogenesis,so as to improve blood flow of the rats of hind limb ischemic.展开更多
Cyclophosphamide is used to treat a variety of tumors. However, the success of the treatment is limited due to severe myelosuppression caused by cyclophosphamide. Administration of cyclophosphamide could significantly...Cyclophosphamide is used to treat a variety of tumors. However, the success of the treatment is limited due to severe myelosuppression caused by cyclophosphamide. Administration of cyclophosphamide could significantly decrease white blood cells (WBCs), platelets, red blood cells (RBCs), as well as hemoglobin level. The aim of this research is to investigate the protective role of Shenfu injection against cyclophosphamide induced myelosuppression. The results showed that Shenfu injection can markedly enhance the level of WBCs, platelets, RBCs, and hemoglobin of myelosuppressed rat. The level of WBCs, platelets, RBCs, and hemoglobin were increased by 70%-100%, 80%-90%, 10%-20% and 10%-20%, respectively. Furthermore, the protective role of Shenfu injection against myelosuppression was confirmed by the microscopic observation of bone marrow sections. In conclusion, Shenfu injection has a potential protective effect against cyclophosphamide-induced myelotoxicity.展开更多
基金Supported by the National Natural Science Foundation of China,No. 82270594National Natural Science Foundation for Youths of China,No. 882002614 and No. 82103151+4 种基金Hunan Provincial Natural Science Foundation of China,No. 2020JJ4853Scientific Research Project of Hunan Provincial Health Commission,No. 202103032097Outstanding Youth Foundation of Hunan Province,No. 2022JJ20092Hunan Provincial Natural Science Foundation of China for Youths,No. 2021JJ40935 and No. 2020JJ5609Wisdom Accumulation and Talent Cultivation Project of Third Xiangya Hospital of Central South University,No. YX202103
文摘BACKGROUND Recently,stem cell therapy has been extensively studied as a promising treatment for decompensated liver cirrhosis(DLC).Technological advances in endoscopic ultrasonography(EUS)have facilitated EUS-guided portal vein(PV)access,through which stem cells can be precisely infused.AIM To investigate the feasibility and safety of fresh autologous bone marrow injection into the PV under EUS guidance in patients with DLC.METHODS Five patients with DLC were enrolled in this study after they provided written informed consent.EUS-guided intraportal bone marrow injection with a 22G FNA needle was performed using a transgastric,transhepatic approach.Several parameters were assessed before and after the procedure for a follow-up period of 12 mo.RESULTS Four males and one female with a mean age of 51 years old participated in this study.All patients had hepatitis B virus-related DLC.EUS-guided intraportal bone marrow injection was performed in all patients successfully without any complications such as hemorrhage.The clinical outcomes of the patients revealed improvements in clinical symptoms,serum albumin,ascites,and Child-Pugh scores throughout the 12-mo follow-up.CONCLUSION The use of EUS-guided fine needle injection for intraportal delivery of bone marrow was feasible and safe and appeared effective in patients with DLC.This treatment may thus be a safe,effective,non-radioactive,and minimally invasive treatment for DLC.
文摘Objective:To explore the effect and mechanism of Xuebijing injection (XBJ) on the hematopoietic homeostasis of bone marrow (BM) in septic mice. Methods:BM cells stimulated with XBJ were analyzed by inverted optical microscope and qPCR, to evaluate the effect of XBJ on differentiation function of BM cells in vitro. Lipopolysaccharide (LPS) 055:B5 at the dose of 20mg/kg was used to establish the sepsis model. To determine the hematopoietic stem cells homeostasis affected by LPS in mice, BM cells were isolated and analyzed by flow cytometry based on the immunophenotypic surface markers. 20ml/kg of XBJ was administered by tail vein once/day after peritoneal injection of LPS. All animals were sacrificed on the fifth day. The frequency of hematopoietic stem cells (HSC) and immune cells in mice were quantified by flow cytometry. The gene expression of transcription factors were detected by qPCR. Results:XBJ promoted myeloid differentiation of BM cells in vitro, which may be related to the mRNA expression of the transcription factors. The results in vivo showed the percentage of BM Lin-SCA-1+c-KIT+(LSK) cells, and Long-term HSCs (LT-HSC) were significantly increased in LPS group. But the percentage of multipotential progenitors (MPPs), granulocyte-monocyte progenitor (GMP) and megakaryocytic-erythroid precursor (MEP) were significantly decreased in LPS group. Whereas, XBJ improved the immune function in sepsis mice by suppression the LSK expansion in vivo. The result of qPCR showed that LSD1 and PU.1 mRNA expression in XBJ group were significantly higher than LPS group and control group respectively. Conclusion:Xuebijing injection can improve immune function in sepsis mice by regulating hematopoietic homeostasis. Its mechanism may be related to the up-regulation of LSD1 and PU.1 gene expressions.
基金by Fundación Lucha contra la Ceguera(FUNDALUCE)to MPVPFundación Robles Chillida to DGA+1 种基金Fundación Séneca,Agencia de Ciencia y Tecnología Región de Murcia(19881/GERM/15 to MVS)the Spanish Ministry of Science and Innovation,Instituto de Salud Carlos III,Fondo Europeo de Desarrollo Regional“Una Manera de Hacer Europa”(SAF2015-67643-P to MVS,PI19/00203 to MPVP and DGA,RD16/0008/0026 to MPVP,RED2018-102499-T to MVS).
文摘Retinal degenerative diseases affecting the outer retina in its many forms(inherited,acquired or induced)are characterized by photoreceptor loss,and represent currently a leading cause of irreversible vision loss in the world.At present,there are very few treatments capable of preventing,recovering or reversing photoreceptor degeneration or the secondary retinal remodeling,which follows photoreceptor loss and can also cause the death of other retinal cells.Thus,these diseases are nowadays one of the greatest challenges in the field of ophthalmological research.Bone marrow derived-mononuclear stem cell transplantation has shown promising results for the treatment of photoreceptor degenerations.These cells may have the potential to slow down photoreceptor loss,and therefore should be applied in the early stages of photoreceptor degenerations.Furthermore,because of their possible paracrine effects,they may have a wide range of clinical applications,since they can potentially impact on several retinal cell types at once and photoreceptor degenerations can involve different cells and/or begin in one cell type and then affect adjacent cells.The intraocular injection of bone marrow derived-mononuclear stem cells also enhances the outcomes of other treatments aimed to protect photoreceptors.Therefore,it is likely that future investigations may combine bone marrow derived-mononuclear stem cell therapy with other systemic or intraocular treatments to obtain greater therapeutic effects in degenerative retinal diseases.
文摘背景:医用水凝胶是具有三维结构网络的新型功能高分子材料,具有出色的生物相容性,目前已在组织工程领域、药物载体领域有广泛研究,但基于组织工程探究医用水凝胶与中医药结合治疗疾病的研究还处于初期探索阶段。因此,通过对医用水凝胶机制作用的剖析,整合医用水凝胶与中医药在研究中联合应用的文章,进而更好地为科研工作者提供思路,对中医药与医用水凝胶联合应用具有重要意义。目的:基于组织工程研究探讨中医药联合医用水凝胶治疗疾病的策略及意义。方法:利用PubMed和中国知网数据库,检索有关中医药联合医用水凝胶在组织工程中应用的文献,检索时间为2010年1月至2022年11月,英文检索词为“hydrogel,traditional Chinese medicine,drug carrier,tissue engineering”,中文检索词为“医用水凝胶、中医药、药物载体、组织工程”。根据纳入与排除标准对所有文章进行初筛后,最终纳入61篇文章进行综述。结果与结论:①中医药联合医用水凝胶的应用虽然在关节内、组织器官内、软组织伤口和组织工程等方面有所涉及,但除了中医药结合水凝胶敷料在临床应用治疗软组织损伤外,其他方面尚处于基础实验阶段。②中医药联合医用水凝胶的发展有着巨大潜力和发展前景,但对于性能要求较高的凝胶在制造方面存在一定难度,理化性质精确掌握难度较大。③目前综合来看可注射水凝胶凭借着简便易用的特点,其在与中医药联合使用可延伸范围较广,可用于关节、器官和组织工程相关疾病的治疗;智能水凝胶有较高的灵敏度和可逆转化性也可满足特殊环境下的使用;将两者结合的中医药使用过程中还需要明确中药成分的作用机制。④中医药联合医用水凝胶治疗疾病的策略应着手于中医药对器官、组织、细胞的治疗作用联合适当种类的医用水凝胶进行匹配,可弥补传统中医给药方式和频繁给药的不足,在组织工程方面可以用水凝胶负载中药干预后的干细胞,或者同时负载中药和干细胞用于相关疾病的治疗。⑤在中医药联合医用水凝胶应用的未来研究中,还需要考虑:应当确保医用水凝胶生物性能可以量化,以不同材料不同制造工艺把握水凝胶特性,制造出所需要的符合应用条件的医用水凝胶;在中医药方面需要对已知中药单体、中药复方提取物的治疗效果和应用机制全面了解剖析,在更明了的机制下实现中医药与医用水凝胶更多更完美的结合;借助医学科技创新能力的不断提高,医用水凝胶可以创新性地结合中医药其他传统治疗方法比如针灸、推拿和拔罐等方式进行多角度运用。
基金supported by the TCM Technology Project of Beijing (No.JJ2007-026)
文摘Objective:To explore the mechanism of acupoint injection of bone marrow mesenchymal stem cells(BM-MSCs) in improving blood flow in the rat with hind limb ischemia.Methods:Twenty-four SD rats were randomly divided into 4 groups:normal control group(n=6),model group(n=6),BM-MSCs acupoint injection group(AI group,n=6) and BM-MSC intramuscular injection group(MI group,n=6).Sanyinjiao(SP 6),Housanli(ST 36),Zhaohai(KI 6),Huantiao(GB 30) and Yanglingquan(GB 34) were selected for the AI group,and five non-acupoints were selected on gastrocnemius and adductor of ischemic hind limbs in the MI group.BM-MSCs were injected to the latter two groups.The rat hind limb ischemia model was established with the method of blocking the femoral artery and its branches.Three weeks after injection of BM-MSCs,in each group,hindlimb adductor and gastrocnemius were taken from the ischemic side.Expressions of vascular endothelial growth factor(VEGF) and transfer growth factor-β1(TGF-β1) in the skeletal muscle were determined with immunohistochemical method,and the small arteries in the skeletal muscle were labeled with α-SMA immunohistochemical staining method,the density of small arteries(number of arterioles /number of muscle fibers) and the number of the blood vessel with VEGF positive expression were calculated.The serum levels of VEGF and nitric oxide(NO) were detected.Results:Compared with the model group,the expression of VEGF and TGF-β1,and the density of small arteries and the number of VEGF-positive blood vessels in the AI group and the MI group significantly increased(both P<0.01).Compared with the MI group,the density of small arteries and the number of VEGF-positive blood vessels in the AI group significantly increased(both P<0.01);Compared with the model group and the normal control group,the serum expression quantity of NO and VEGF in the AI group and the MI group were significantly increased(P<0.01).Conclusions:Acuppoint injection of BM-MSCs secrets more VEGF,TGF-β1 and NO to increase angiogenesis and arteriogenesis,so as to improve blood flow of the rats of hind limb ischemic.
基金Chinese Medicine in Zhejiang Province Science and Technology Project (Grant No. 2007CA059)
文摘Cyclophosphamide is used to treat a variety of tumors. However, the success of the treatment is limited due to severe myelosuppression caused by cyclophosphamide. Administration of cyclophosphamide could significantly decrease white blood cells (WBCs), platelets, red blood cells (RBCs), as well as hemoglobin level. The aim of this research is to investigate the protective role of Shenfu injection against cyclophosphamide induced myelosuppression. The results showed that Shenfu injection can markedly enhance the level of WBCs, platelets, RBCs, and hemoglobin of myelosuppressed rat. The level of WBCs, platelets, RBCs, and hemoglobin were increased by 70%-100%, 80%-90%, 10%-20% and 10%-20%, respectively. Furthermore, the protective role of Shenfu injection against myelosuppression was confirmed by the microscopic observation of bone marrow sections. In conclusion, Shenfu injection has a potential protective effect against cyclophosphamide-induced myelotoxicity.