In order to investigate the origin of neointimal smooth muscle cells in transplant arterio- sclerosis in rat aortic allograft, sex-mismatched bone marrow transplantation was performed from male Wistar rats to female W...In order to investigate the origin of neointimal smooth muscle cells in transplant arterio- sclerosis in rat aortic allograft, sex-mismatched bone marrow transplantation was performed from male Wistar rats to female Wistar rats. Four weeks after transplantation, the aortic transplant model was established by means of micro-surgery in rats. The recipients were divided into 4 groups: female Wistar-female Wistar aortic isografts, female SD-female Wistar aortic allografts, male SD-male Wis- tar aortic allografts, female SD-chimera Wistar aortic allografts. Eight weeks after transplantation, aortic grafts were removed at autopsy and processed for histological evaluation and immunohisto- chemistry. The results indicated that excessive accumulation of α-SMA-positive smooth muscle cells resulted in significant neointima formation and vascular lumen stricture in rat aortic allografts. Neointima assay revealed that the neointimal area and NIA/MA ratio of transplanted artery were sig- nificantly increased in all of aortic allograft groups as compared with those in aortic isograft group (P<0.01). Neointimal smooth muscle cells were harvested from cryostat sections of aortic allograft by microdissection method. The Sry gene-specific PCR was performed, and the result showed that a dis- tinct DNA band of 225 bp emerged in the male-male aortic allograft group and chimera aortic al- lograft group respectively, but not in the female-female aortic allograft group. It was suggested that recipient bone-marrow cells, as the origin of neointimal smooth muscle cells, contributed to the pathological neointimal hyperplasia of aortic allograft and transplant arteriosclerosis.展开更多
THIS year＇s International AIDS Society Conference on HIV Pathogenesis, Treatment and Preven-／tion, held in Kuala Lumpur, Malaysia, made major headlines when Timothy Hendch, an American doctor, announced that two mor...THIS year＇s International AIDS Society Conference on HIV Pathogenesis, Treatment and Preven-／tion, held in Kuala Lumpur, Malaysia, made major headlines when Timothy Hendch, an American doctor, announced that two more cancer patients may have been cured of HIV after receiving bone-marrow transplants to treat lymphoma. Both patients had been taking retroviral medication, and continued to do so after the transplants as their viral levels sank until doctors were unable to find any traces of HIV in the patients＇ blood.展开更多
AIM: To investigate the effect of bone-marrow mesenchymal stem cells (BM MSCs) on the intestinal mucosa barrier in ischemia/reperfusion (I/R) injury. METHODS: BM MSCs were isolated from male Sprague-Dawley rats by den...AIM: To investigate the effect of bone-marrow mesenchymal stem cells (BM MSCs) on the intestinal mucosa barrier in ischemia/reperfusion (I/R) injury. METHODS: BM MSCs were isolated from male Sprague-Dawley rats by density gradient centrifugation, cultured, and analyzed by flow cytometry. I/R injury was induced by occlusion of the superior mesenteric artery for 30 min. Rats were treated with saline, BM MSCs (via intramucosal injection) or tumor necrosis factor (TNF)-α blocking antibodies (via the tail vein). I/R injury was assessed using transmission electron microscopy, hematoxylin and eosin (HE) staining, immunohistochemistry, western blotting and enzyme linked immunosorbent assay.RESULTS: Intestinal permeability increased, tight junctions (TJs) were disrupted, and zona occludens 1 (ZO-1) was downregulated after I/R injury. BM MSCs reduced intestinal mucosal barrier destruction, ZO-1 downregulation, and TJ disruption. The morphological abnormalities after intestinal I/R injury positively correlated with serum TNF-α levels. Administration of anti-TNF-α IgG or anti-TNF-α receptor 1 antibodies attenuated the intestinal ultrastructural changes, ZO-1 downregulation, and TJ disruption. CONCLUSION: Altered serum TNF-α levels play an important role in the ability of BM MSCs to protect against intestinal I/R injury.展开更多
Granulopoiesis in murine bone-marrow is regulated by both intrinsic and extrinsic factors(including hormones, drugs, inflammatory mediators and cytokines). Eosinophils, a minor subpopulation of circulating leukocytes,...Granulopoiesis in murine bone-marrow is regulated by both intrinsic and extrinsic factors(including hormones, drugs, inflammatory mediators and cytokines). Eosinophils, a minor subpopulation of circulating leukocytes, which remains better understood in its contributions to tissue injury in allergic disease than in its presumably beneficial actions in host defense, provide a striking example of joint regulation of granulopoiesis within murine bone-marrow by all of these classes of extrinsic factors. We first described the upregulation of eosinopoiesis in bone-marrow of allergen-sensitized mice following airway allergen challenge. Over the last decade, we were able to show a critical role for endogenous glucocorticoid hormones and cytokines in mediating this phenomenon through modification of cytokine effects, thereby supporting a positive association between stress hormones and allergic reactions. We have further shown that cysteinylleukotrienes(Cys LT), a major proinflammatory class of lipid mediators, generated through the 5-lipoxygenase pathway, upregulate bone-marrow eosinopoiesis in vivo and in vitro. Cys LT mediate the positive effects of drugs(indomethacin and aspirin) and of proallergic cytokines(eotaxin/CCL11 and interleukin-13) on in vitro eosinopoiesis. While these actions of endogenous GC and Cys LT might seem unrelated and even antagonistic, we demonstrated a critical partnership of these mediators in vivo, shedding light on mechanisms linking stress to allergy: GC are required for Cys LT-mediated upregulation of bone-marrow eosinopoiesis in vivo, but also attenuate subsequent ex vivo responses to Cys LT. GC and Cys LT therefore work together to induce eosinophilia, but through subtle regulatory mechanisms also limit the magnitude of subsequent bone-marrow responses to allergen.展开更多
Adult derived mononuclear bone marrow cells are a good alternative as cell therapy. These cells are capable of significantly improve survival rate of Wistar rats with acetaminophen (APAP) induced acute liver failure i...Adult derived mononuclear bone marrow cells are a good alternative as cell therapy. These cells are capable of significantly improve survival rate of Wistar rats with acetaminophen (APAP) induced acute liver failure in ten days. However, long term of cell therapy is not deeply studied in the literature. Here, we report an extramedullary hematopoiesis process derived from transplanted mononuclear bone marrow cells in the liver of rats 10 days after APAP injection. This result indicates that liver maintains an adequate microenvironment for the occurrence of extramedullary hematopoiesis process. The consequence of this finding deserves more studies.展开更多
背景:非创伤性股骨头坏死的发病机制尚不明确,其中血脂代谢紊乱是引起非创伤性股骨头坏死的重要假说,通过调节血脂代谢来抑制股骨头坏死的进展,已成为当前治疗非创伤性股骨头坏死的重要方法。目的:综述非创伤性股骨头坏死与脂质代谢紊...背景:非创伤性股骨头坏死的发病机制尚不明确,其中血脂代谢紊乱是引起非创伤性股骨头坏死的重要假说,通过调节血脂代谢来抑制股骨头坏死的进展,已成为当前治疗非创伤性股骨头坏死的重要方法。目的:综述非创伤性股骨头坏死与脂质代谢紊乱的关系及治疗研究进展。方法:以“股骨头坏死,非创伤性股骨头坏死,骨坏死,骨与脂质代谢,股骨头坏死与脂质,股骨头坏死机制,股骨头坏死通路,股骨头坏死治疗”为中文检索词,以“osteonecrosis of femoral head,Nontraumatic osteonecrosis of femoral head,femoral head necrosis,osteonecrosis and lipid,lipid metabolism osteonecrosis,polymorphisms osteonecrosis of femoral head,pathway osteonecrosis of femoral head,steroid-induced osteonecrosis of the femoral head,alcohol-induced osteonecrosis of femoral head”为英文检索词,检索中国知网、万方医学网、中华医学期刊数据库、PubMed数据库,最终纳入104篇文献进行归纳总结。结果与结论:①股骨头坏死患者常伴随血脂异常,研究发现总胆固醇、三酰甘油、低密度脂蛋白胆固醇、载脂蛋白B水平升高与载脂蛋白A1水平降低是引起股骨头坏死的危险因素,并且不同诱因的股骨头坏死患者血脂水平存在差异;②激素和酒精作为非创伤性股骨头坏死的两大诱因,可以诱导骨髓间充质干细胞的成脂分化,使骨髓腔内脂肪细胞增多、脂滴聚集,最终导致股骨头坏死;③许多与脂质代谢相关的分子和脂肪因子,如脂联素、瘦素、脂质运载蛋白2等都被证实与股骨头坏死有关;④过氧化物酶体增殖物激活受体γ、Wnt/β-catenin、腺苷酸环化蛋白激酶等信号通路可以改变骨髓间充质干细胞的成骨-成脂分化潜能,从而参与股骨头坏死的发生发展;磷脂酰肌醇3激酶/蛋白激酶B、骨形态发生蛋白2等脂代谢信号通路也与股骨头坏死有关,可能通过调节脂质代谢影响股骨头坏死的进展;⑤研究发现,虫草素、三七总皂苷、骨蚀灵胶囊等中药和他汀类药物可以通过改善脂质代谢紊乱达到治疗非创伤性股骨头坏死的效果。展开更多
背景:纳米细胞囊泡具有再上皮化、抗氧化、抗炎以及调节细胞外基质重塑等功能,凋亡小体具有免疫调节作用,因此二者结合所形成的纳米融合囊泡可协同促进糖尿病皮肤创面愈合。目的:探讨纳米融合囊泡对糖尿病小鼠皮肤创面的愈合作用。方法...背景:纳米细胞囊泡具有再上皮化、抗氧化、抗炎以及调节细胞外基质重塑等功能,凋亡小体具有免疫调节作用,因此二者结合所形成的纳米融合囊泡可协同促进糖尿病皮肤创面愈合。目的:探讨纳米融合囊泡对糖尿病小鼠皮肤创面的愈合作用。方法:①材料制备及表征:分离提取C57BL/6J乳鼠原代骨髓间充质干细胞纳米囊泡和C57BL/6J小鼠骨髓来源中性粒细胞凋亡小体,将二者结合采用微型挤出机制备纳米融合囊泡。②体外实验:采用MTT检测不同浓度纳米融合囊泡对NIH-3T3细胞和人脐静脉内皮细胞的增殖作用;采用活性氧荧光探针检测纳米融合囊泡对过氧化氢干预的NIH-3T3细胞的抗氧化作用;采用实时定量RT-qPCR法检测纳米融合囊泡对脂多糖引发的RAW 264.7巨噬细胞炎症反应的抑制效果。③体内实验:36只雄性C57BL/6J小鼠构建糖尿病小鼠模型,造模成功后在糖尿病小鼠脊柱两侧使用打孔机分别制备直径6 mm的2个圆形创面,采用随机数字表法分为3组,对照组创缘皮下注射0.1 mL磷酸盐缓冲液,纳米囊泡组注射0.1 mL 25μg/mL纳米囊泡,纳米融合囊泡组注射0.1 mL 25μg/mL纳米融合囊泡,连续治疗3 d,观察创面愈合情况与组织形态学变化。结果与结论:①体外实验:纳米融合囊泡在质量浓度为0-100μg/mL时均无毒性作用,且可促进NIH-3T3细胞和人脐静脉内皮细胞的增殖,其中25μg/mL纳米融合囊泡促进NIH-3T3细胞增殖的效果最明显,而人脐静脉内皮细胞的存活率则随着纳米融合囊泡质量浓度的增加不断增强。纳米融合囊泡具有良好的抗氧化效果,与过氧化氢组相比,纳米囊泡组和纳米融合囊泡组的活性氧荧光信号依次减弱。此外,纳米融合囊泡还具有抗炎能力,降低了脂多糖诱导的巨噬细胞炎症反应。②体内实验:苏木精-伊红染色与Masson染色显示,与对照组相比,术后第6天纳米囊泡组和纳米融合囊泡组创面均表达出丰富的胶原纤维以及肉芽组织,其中以纳米融合囊泡组最多;术后第12天,纳米融合囊泡组创面显著缩小,且愈合速度显著快于其他组,促创面愈合效果最为显著。结果表明,纳米融合囊泡能够展现出促细胞增殖、抗氧化和抗炎特性,从而在促进糖尿病小鼠皮肤创面愈合过程中发挥积极作用。展开更多
基金grants from the National Natural Sciences Foundation of China (No. 30271242, 30371396)
文摘In order to investigate the origin of neointimal smooth muscle cells in transplant arterio- sclerosis in rat aortic allograft, sex-mismatched bone marrow transplantation was performed from male Wistar rats to female Wistar rats. Four weeks after transplantation, the aortic transplant model was established by means of micro-surgery in rats. The recipients were divided into 4 groups: female Wistar-female Wistar aortic isografts, female SD-female Wistar aortic allografts, male SD-male Wis- tar aortic allografts, female SD-chimera Wistar aortic allografts. Eight weeks after transplantation, aortic grafts were removed at autopsy and processed for histological evaluation and immunohisto- chemistry. The results indicated that excessive accumulation of α-SMA-positive smooth muscle cells resulted in significant neointima formation and vascular lumen stricture in rat aortic allografts. Neointima assay revealed that the neointimal area and NIA/MA ratio of transplanted artery were sig- nificantly increased in all of aortic allograft groups as compared with those in aortic isograft group (P<0.01). Neointimal smooth muscle cells were harvested from cryostat sections of aortic allograft by microdissection method. The Sry gene-specific PCR was performed, and the result showed that a dis- tinct DNA band of 225 bp emerged in the male-male aortic allograft group and chimera aortic al- lograft group respectively, but not in the female-female aortic allograft group. It was suggested that recipient bone-marrow cells, as the origin of neointimal smooth muscle cells, contributed to the pathological neointimal hyperplasia of aortic allograft and transplant arteriosclerosis.
文摘THIS year＇s International AIDS Society Conference on HIV Pathogenesis, Treatment and Preven-／tion, held in Kuala Lumpur, Malaysia, made major headlines when Timothy Hendch, an American doctor, announced that two more cancer patients may have been cured of HIV after receiving bone-marrow transplants to treat lymphoma. Both patients had been taking retroviral medication, and continued to do so after the transplants as their viral levels sank until doctors were unable to find any traces of HIV in the patients＇ blood.
基金Supported by Natural Science Foundation of China, No.81270528the Natural Science Foundation of Tianjin, No. 08JCYBJC08400, No. 11JCZDJC27800 and No. 12JCZDJC25200the Technology Foundation of Health Bureau in Tianjin, No.2011KY11
文摘AIM: To investigate the effect of bone-marrow mesenchymal stem cells (BM MSCs) on the intestinal mucosa barrier in ischemia/reperfusion (I/R) injury. METHODS: BM MSCs were isolated from male Sprague-Dawley rats by density gradient centrifugation, cultured, and analyzed by flow cytometry. I/R injury was induced by occlusion of the superior mesenteric artery for 30 min. Rats were treated with saline, BM MSCs (via intramucosal injection) or tumor necrosis factor (TNF)-α blocking antibodies (via the tail vein). I/R injury was assessed using transmission electron microscopy, hematoxylin and eosin (HE) staining, immunohistochemistry, western blotting and enzyme linked immunosorbent assay.RESULTS: Intestinal permeability increased, tight junctions (TJs) were disrupted, and zona occludens 1 (ZO-1) was downregulated after I/R injury. BM MSCs reduced intestinal mucosal barrier destruction, ZO-1 downregulation, and TJ disruption. The morphological abnormalities after intestinal I/R injury positively correlated with serum TNF-α levels. Administration of anti-TNF-α IgG or anti-TNF-α receptor 1 antibodies attenuated the intestinal ultrastructural changes, ZO-1 downregulation, and TJ disruption. CONCLUSION: Altered serum TNF-α levels play an important role in the ability of BM MSCs to protect against intestinal I/R injury.
文摘Granulopoiesis in murine bone-marrow is regulated by both intrinsic and extrinsic factors(including hormones, drugs, inflammatory mediators and cytokines). Eosinophils, a minor subpopulation of circulating leukocytes, which remains better understood in its contributions to tissue injury in allergic disease than in its presumably beneficial actions in host defense, provide a striking example of joint regulation of granulopoiesis within murine bone-marrow by all of these classes of extrinsic factors. We first described the upregulation of eosinopoiesis in bone-marrow of allergen-sensitized mice following airway allergen challenge. Over the last decade, we were able to show a critical role for endogenous glucocorticoid hormones and cytokines in mediating this phenomenon through modification of cytokine effects, thereby supporting a positive association between stress hormones and allergic reactions. We have further shown that cysteinylleukotrienes(Cys LT), a major proinflammatory class of lipid mediators, generated through the 5-lipoxygenase pathway, upregulate bone-marrow eosinopoiesis in vivo and in vitro. Cys LT mediate the positive effects of drugs(indomethacin and aspirin) and of proallergic cytokines(eotaxin/CCL11 and interleukin-13) on in vitro eosinopoiesis. While these actions of endogenous GC and Cys LT might seem unrelated and even antagonistic, we demonstrated a critical partnership of these mediators in vivo, shedding light on mechanisms linking stress to allergy: GC are required for Cys LT-mediated upregulation of bone-marrow eosinopoiesis in vivo, but also attenuate subsequent ex vivo responses to Cys LT. GC and Cys LT therefore work together to induce eosinophilia, but through subtle regulatory mechanisms also limit the magnitude of subsequent bone-marrow responses to allergen.
文摘Adult derived mononuclear bone marrow cells are a good alternative as cell therapy. These cells are capable of significantly improve survival rate of Wistar rats with acetaminophen (APAP) induced acute liver failure in ten days. However, long term of cell therapy is not deeply studied in the literature. Here, we report an extramedullary hematopoiesis process derived from transplanted mononuclear bone marrow cells in the liver of rats 10 days after APAP injection. This result indicates that liver maintains an adequate microenvironment for the occurrence of extramedullary hematopoiesis process. The consequence of this finding deserves more studies.
文摘背景:非创伤性股骨头坏死的发病机制尚不明确,其中血脂代谢紊乱是引起非创伤性股骨头坏死的重要假说,通过调节血脂代谢来抑制股骨头坏死的进展,已成为当前治疗非创伤性股骨头坏死的重要方法。目的:综述非创伤性股骨头坏死与脂质代谢紊乱的关系及治疗研究进展。方法:以“股骨头坏死,非创伤性股骨头坏死,骨坏死,骨与脂质代谢,股骨头坏死与脂质,股骨头坏死机制,股骨头坏死通路,股骨头坏死治疗”为中文检索词,以“osteonecrosis of femoral head,Nontraumatic osteonecrosis of femoral head,femoral head necrosis,osteonecrosis and lipid,lipid metabolism osteonecrosis,polymorphisms osteonecrosis of femoral head,pathway osteonecrosis of femoral head,steroid-induced osteonecrosis of the femoral head,alcohol-induced osteonecrosis of femoral head”为英文检索词,检索中国知网、万方医学网、中华医学期刊数据库、PubMed数据库,最终纳入104篇文献进行归纳总结。结果与结论:①股骨头坏死患者常伴随血脂异常,研究发现总胆固醇、三酰甘油、低密度脂蛋白胆固醇、载脂蛋白B水平升高与载脂蛋白A1水平降低是引起股骨头坏死的危险因素,并且不同诱因的股骨头坏死患者血脂水平存在差异;②激素和酒精作为非创伤性股骨头坏死的两大诱因,可以诱导骨髓间充质干细胞的成脂分化,使骨髓腔内脂肪细胞增多、脂滴聚集,最终导致股骨头坏死;③许多与脂质代谢相关的分子和脂肪因子,如脂联素、瘦素、脂质运载蛋白2等都被证实与股骨头坏死有关;④过氧化物酶体增殖物激活受体γ、Wnt/β-catenin、腺苷酸环化蛋白激酶等信号通路可以改变骨髓间充质干细胞的成骨-成脂分化潜能,从而参与股骨头坏死的发生发展;磷脂酰肌醇3激酶/蛋白激酶B、骨形态发生蛋白2等脂代谢信号通路也与股骨头坏死有关,可能通过调节脂质代谢影响股骨头坏死的进展;⑤研究发现,虫草素、三七总皂苷、骨蚀灵胶囊等中药和他汀类药物可以通过改善脂质代谢紊乱达到治疗非创伤性股骨头坏死的效果。
文摘背景:纳米细胞囊泡具有再上皮化、抗氧化、抗炎以及调节细胞外基质重塑等功能,凋亡小体具有免疫调节作用,因此二者结合所形成的纳米融合囊泡可协同促进糖尿病皮肤创面愈合。目的:探讨纳米融合囊泡对糖尿病小鼠皮肤创面的愈合作用。方法:①材料制备及表征:分离提取C57BL/6J乳鼠原代骨髓间充质干细胞纳米囊泡和C57BL/6J小鼠骨髓来源中性粒细胞凋亡小体,将二者结合采用微型挤出机制备纳米融合囊泡。②体外实验:采用MTT检测不同浓度纳米融合囊泡对NIH-3T3细胞和人脐静脉内皮细胞的增殖作用;采用活性氧荧光探针检测纳米融合囊泡对过氧化氢干预的NIH-3T3细胞的抗氧化作用;采用实时定量RT-qPCR法检测纳米融合囊泡对脂多糖引发的RAW 264.7巨噬细胞炎症反应的抑制效果。③体内实验:36只雄性C57BL/6J小鼠构建糖尿病小鼠模型,造模成功后在糖尿病小鼠脊柱两侧使用打孔机分别制备直径6 mm的2个圆形创面,采用随机数字表法分为3组,对照组创缘皮下注射0.1 mL磷酸盐缓冲液,纳米囊泡组注射0.1 mL 25μg/mL纳米囊泡,纳米融合囊泡组注射0.1 mL 25μg/mL纳米融合囊泡,连续治疗3 d,观察创面愈合情况与组织形态学变化。结果与结论:①体外实验:纳米融合囊泡在质量浓度为0-100μg/mL时均无毒性作用,且可促进NIH-3T3细胞和人脐静脉内皮细胞的增殖,其中25μg/mL纳米融合囊泡促进NIH-3T3细胞增殖的效果最明显,而人脐静脉内皮细胞的存活率则随着纳米融合囊泡质量浓度的增加不断增强。纳米融合囊泡具有良好的抗氧化效果,与过氧化氢组相比,纳米囊泡组和纳米融合囊泡组的活性氧荧光信号依次减弱。此外,纳米融合囊泡还具有抗炎能力,降低了脂多糖诱导的巨噬细胞炎症反应。②体内实验:苏木精-伊红染色与Masson染色显示,与对照组相比,术后第6天纳米囊泡组和纳米融合囊泡组创面均表达出丰富的胶原纤维以及肉芽组织,其中以纳米融合囊泡组最多;术后第12天,纳米融合囊泡组创面显著缩小,且愈合速度显著快于其他组,促创面愈合效果最为显著。结果表明,纳米融合囊泡能够展现出促细胞增殖、抗氧化和抗炎特性,从而在促进糖尿病小鼠皮肤创面愈合过程中发挥积极作用。
