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
目的与单纯髓芯减压(core decompression,CD)治疗相比,探讨双通道CD联合髓腔冲洗技术对非创伤性股骨头坏死(osteonecrosis of the femoral head,ONFH)塌陷进展以及临床结果的影响。方法回顾性分析2024年1月—10月因ONFH行双通道CD联合...目的与单纯髓芯减压(core decompression,CD)治疗相比,探讨双通道CD联合髓腔冲洗技术对非创伤性股骨头坏死(osteonecrosis of the femoral head,ONFH)塌陷进展以及临床结果的影响。方法回顾性分析2024年1月—10月因ONFH行双通道CD联合髓腔冲洗治疗且符合选择标准的19例(30髋)患者(CD+冲洗组)临床资料,按照1∶2比例纳入年龄、性别、身体质量指数(body mass index,BMI)匹配的54例(60髋)单纯CD患者作为对照(CD组)。两组患者性别、年龄、BMI、手术侧别、ONFH类型以及术前国际骨循环协会(ARCO)分期、骨髓水肿分期、疼痛视觉模拟评分(VAS)、Harris评分等基线资料比较,差异均无统计学意义(P>0.05)。记录并比较两组患者术后住院时间以及并发症发生情况;术前及术后出院时VAS评分,计算手术前后差值(变化值);术前及术后出院、3个月时Harris评分。随访期间行X线片、CT和双髋MRI复查,术后3个月行ARCO分期和骨髓水肿分期,并与术前比较确定是否存在影像学进展或缓解。结果术后两组患者切口均Ⅰ期愈合,无感染、股骨颈骨折等手术相关并发症发生。两组患者均获随访,CD+冲洗组随访时间为(146.8±27.7)d,CD组为(164.3±48.2)d,组间差异无统计学意义(t=1.840,P=0.069)。两组术后住院时间差异无统计学意义(P>0.05)。术后出院时CD+冲洗组VAS评分低于CD组,变化值高于CD组,差异均有统计学意义(P<0.05)。CD+冲洗组术后出院时、3个月时Harris评分均高于CD组,差异均有统计学意义(P<0.05);组内随时间延长,Harris评分逐渐增高,各时间点间差异均有统计学意义(P<0.05)。影像学复查示,术后3个月两组ARCO分期以及影像学进展差异均无统计学意义(P>0.05);而CD+冲洗组骨髓水肿分期以及骨髓水肿缓解均优于CD组,差异有统计学意义(P<0.05)。结论双通道CD联合髓腔冲洗技术能明显减轻ONFH患者髋关节疼痛和改善关节功能,缓解股骨头骨髓水肿程度,延缓ONFH进展。展开更多
股骨头坏死(osteonecrosis of the femoral head,ONFH)是一种致残性骨科疾病,以进行性股骨头塌陷伴骨小梁、关节软骨结构破坏为病理特征,导致髋关节疼痛及进行性功能障碍。骨髓间充质干细胞来源细胞外囊泡(BMSC-derived exosomes,BMSC-E...股骨头坏死(osteonecrosis of the femoral head,ONFH)是一种致残性骨科疾病,以进行性股骨头塌陷伴骨小梁、关节软骨结构破坏为病理特征,导致髋关节疼痛及进行性功能障碍。骨髓间充质干细胞来源细胞外囊泡(BMSC-derived exosomes,BMSC-EVs)在组织修复和再生方面有良好的前景,免疫原性和致瘤性较低,影响成骨、成血管和免疫调节。本文综述了BMSC-EVs在ONFH中的治疗效果及其潜在机制,为ONFH的治疗提供理论依据。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.
文摘目的与单纯髓芯减压(core decompression,CD)治疗相比,探讨双通道CD联合髓腔冲洗技术对非创伤性股骨头坏死(osteonecrosis of the femoral head,ONFH)塌陷进展以及临床结果的影响。方法回顾性分析2024年1月—10月因ONFH行双通道CD联合髓腔冲洗治疗且符合选择标准的19例(30髋)患者(CD+冲洗组)临床资料,按照1∶2比例纳入年龄、性别、身体质量指数(body mass index,BMI)匹配的54例(60髋)单纯CD患者作为对照(CD组)。两组患者性别、年龄、BMI、手术侧别、ONFH类型以及术前国际骨循环协会(ARCO)分期、骨髓水肿分期、疼痛视觉模拟评分(VAS)、Harris评分等基线资料比较,差异均无统计学意义(P>0.05)。记录并比较两组患者术后住院时间以及并发症发生情况;术前及术后出院时VAS评分,计算手术前后差值(变化值);术前及术后出院、3个月时Harris评分。随访期间行X线片、CT和双髋MRI复查,术后3个月行ARCO分期和骨髓水肿分期,并与术前比较确定是否存在影像学进展或缓解。结果术后两组患者切口均Ⅰ期愈合,无感染、股骨颈骨折等手术相关并发症发生。两组患者均获随访,CD+冲洗组随访时间为(146.8±27.7)d,CD组为(164.3±48.2)d,组间差异无统计学意义(t=1.840,P=0.069)。两组术后住院时间差异无统计学意义(P>0.05)。术后出院时CD+冲洗组VAS评分低于CD组,变化值高于CD组,差异均有统计学意义(P<0.05)。CD+冲洗组术后出院时、3个月时Harris评分均高于CD组,差异均有统计学意义(P<0.05);组内随时间延长,Harris评分逐渐增高,各时间点间差异均有统计学意义(P<0.05)。影像学复查示,术后3个月两组ARCO分期以及影像学进展差异均无统计学意义(P>0.05);而CD+冲洗组骨髓水肿分期以及骨髓水肿缓解均优于CD组,差异有统计学意义(P<0.05)。结论双通道CD联合髓腔冲洗技术能明显减轻ONFH患者髋关节疼痛和改善关节功能,缓解股骨头骨髓水肿程度,延缓ONFH进展。
文摘股骨头坏死(osteonecrosis of the femoral head,ONFH)是一种致残性骨科疾病,以进行性股骨头塌陷伴骨小梁、关节软骨结构破坏为病理特征,导致髋关节疼痛及进行性功能障碍。骨髓间充质干细胞来源细胞外囊泡(BMSC-derived exosomes,BMSC-EVs)在组织修复和再生方面有良好的前景,免疫原性和致瘤性较低,影响成骨、成血管和免疫调节。本文综述了BMSC-EVs在ONFH中的治疗效果及其潜在机制,为ONFH的治疗提供理论依据。
