Bone From Blood: Characteristics and Clinical Implications of Circulating Osteogenic Progenitor (COP) Cells

Circulating osteogenic progenitor (COP) cells are a population of cells in the peripheral blood with the capacity for bone formation, as well as broader differentiation into mesoderm-like cells in vitro. Although some of their biological characteristics are documented in vitro, their role in diseases of the musculoskeletal system remains yet to be fully evaluated. In this review, we provide an overview of the role of COP cells in a number of physiological and pathological conditions, as well as identify areas for future research. In addition, we suggest possible areas for clinical utilization in the management of musculoskeletal diseases. © 2020 American Society for Bone and Mineral Research (ASBMR).     

通痹灵对胶原诱导性关节炎大鼠滑膜组织血管内皮生长因子表达水平的影响

目的 观察通痹灵对胶原诱导性关节炎（CIA）大鼠关节滑膜组织炎症和血管内皮生长因子（VEGF）表达水平的影响，以探讨通痹灵治疗类风湿性关节炎（RA）的作用机理。方法 大鼠尾根部皮下注射Ⅱ型胶原蛋白建立CIA模型，分组给药治疗，给药37d后处死动物，对动物膝关节滑膜病理切片后分别常规HE染色和免疫组化染色。对HE染色切片用显微镜观察炎症细胞浸润，巨噬细胞增生和纤维增生情况，对免疫组化染色切片观察血管内皮生长因子（VEGF）阳性细胞情况以了解各组动物关节滑膜VEGF的表达水平。结果 HE染色切片显示通痹灵高剂量组滑膜炎症细胞浸润，巨噬样A型细胞增生和纤维组织增生的程度均比模型组低（P＜0．05或P＜0．01），并与正常组相仿（P＞0．05）。免疫组化染色切片显示通通痹灵和雷公藤高剂量组均能降低滑膜VEGF表达水平（P＜0．05）。结论 通痹灵有改善大鼠关节滑膜炎症，抑制滑膜VEGF表达作用，这可能是通痹灵治疗关节炎取得临床疗效的机理之一。     

电针对血管性痴呆大鼠学习记忆和血红素氧化酶的影响

[目的]探讨电针对血管性痴呆（VD）大鼠学习记忆障碍的治疗效应及其作用的分子机制.[方法]SD雄性大鼠60只,除假手术组10只外,其他大鼠均采用4-血管阻断法复制VD模型,存活大鼠随机分为电针组14只,尼莫通组13只,模型组13只;电针组针刺“百会”和“大椎”两穴,尼莫通组以12 mg/kg灌胃给药,假手术组与模型组未予任何治疗.采用Morris水迷宫观察治疗20d后各组大鼠在学习记忆方面的变化,并检测血红素氧化酶（HO）的蛋白表达和信使核糖核酸（mRNA）表达.[结果]与假手术组比较,模型组逃避潜伏期、HO-1蛋白表达、HO-1 mRNA表达增高（P＜0.01）;与模型组比较,电针组、尼莫通组逃避潜伏期、HO-1蛋白表达均显著减少（P＜0.01）,H0-1 mRNA表达水平均降低（P＜0.05）;电针组与尼莫通组比较,各指标均无显著性差异（P＞0.05）.[结论]电针治疗改善VD模型大鼠学习记忆能力与尼莫通治疗相仿,两法均可能与减少海马和皮质神经元细胞HO-1蛋白表达及H0-1 mRNA表达有关.     

Heparin-Conjugated PCL Scaffolds Fabricated by Electrospinning and Loaded with Fibroblast Growth Factor 2

A biodegradable poly(ε-caprolactone) (PCL) was synthesized by ring-opening polymerization of ε-caprolactone catalyzed by Sn(Oct)₂/BDO, followed by the heparin conjugation using EDC/NHS chemistry. The structure of the heparin–PCL conjugate was characterized by ¹H-NMR and GPC. The results of static contact angle and water uptake ratio measurements also confirmed the conjugation of heparin with the polyester. Its in vitro anticoagulation time was substantially extended, as evidenced by activated partial thromboplastin time (APTT) testing. Afterwards the conjugate was electrospun into small-diameter tubular scaffolds and loaded with Fibroblast Growth Factor 2 (FGF2) in aqueous solution. The loading efficiency was assayed by enzyme-linked immunosorbent assay (ELISA); the results indicated that the conjugate holds a higher loading efficiency than the blank polyester. The viability of released FGF2 was evaluated by MTT and cell adhesion tests. The amount and morphology of cells were significantly improved after FGF2 loading onto the electrospun heparin–PCL vascular scaffolds.     

In vitro study on hemocompatibility and cytocompatibility of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)

Samples of polyhydroxybutyrate (PHB), poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) containing 4–20% (mol/mol) 3-hydroxyhexanoate (3HHx) were characterized as potential components of blood-contact biomaterials. In an erythrocyte contact hemolysis assay, all tested PHBHHx films had substantially reduced reactivity, typically displaying about 2-fold less hemolytic activity compared with that of PHBV. Both 12% and 20% containing PHBHHx also bound less platelets than other films. After a 120-min exposure to platelet-rich plasma (PRP), few platelets adhered to the 12% and 20% containing PHBHHx films, while numerous platelets were seen on PHBV. Surface properties investigation suggested along with increasing 3HHx content, PHBHHx co-polymer films became smoother and smoother, which may contribute to lower platelet adhesion of PHBHHx containing high HHx content in a short-term contact to platelet-rich plasma. In a long-term contact to PRP, the difference in crystallization of PHBVand PHBHHx can be a critical parameter for platelet adhesion. Human umbilical vein endothelial cells (HUVECs) grew well on PHBHHx containing high content of 3HHx, indicating that both had good biocompatibility with HUVECs. While gelatin-coated or lipase-treated polyesters improved HUVECs proliferation compared with that on uncoated films, platelet adhesion was also decreased on gelatin-coated polyester. The hemocompatibility and biocompatibility of PHBHHx film were markedly improved. Thus, PHBHHx, particularly the surface-modified PHBHHx film, is promising for blood-contact materials.     

Direct percutaneous carotid artery stenting with distal protection: technical case report

Abstract

We describe the technique of percutaneous carotid artery stent placement with distal protection in a patient in whom marked innominate artery ectasia prevented transfemoral access to the right common carotid artery. After induction of general anesthesia, ultrasound was used to guide direct puncture of the common carotid artery followed by the introduction of a 5 French sheath. A GuardWire distal protection balloon (Medtronic, Santa Rosa, CA) was placed distal to the lesion and deployed at nominal diameter. A balloon-expandable stent was deployed without difficulty. Following stent placement, angiography demonstrated improved flow in the entire right carotid artery territory. There were no complications related to cervical soft tissue damage or clinical embolism. The patient tolerated the procedure well and was discharged in 24 hours. Direct carotid access is acceptable in select patients in whom a transfemoral, brachial, or transradial approach is technically difficult. The use of distal cerebral protection devices may reduce cerebral embolism associated with these procedures.     

Atherosclerosis,vascular amyloidosis and brain hypoperfusion in the pathogenesis of sporadic Alzheimer's disease

Abstract

We postulate that severe atherosclerotic occlusion of the circle of Willis and leptomeningeal arteries is an important factor in the pathogenesis of some sporadic Alzheimer's disease (AD) cases. These arterial stenoses are complicated by an overwhelming amyloid accumulation in the walls of leptomeningeal and cortical arteries resulting in a significant decrease in perfusion pressure and consequent ischemia/hypoxia of the brain tissue. We also propose that the distal areas of the white matter (WM) will be the first affected by a lack of oxygen and nutrients. Our hypotheses are supported by the following observations: (1) the number of stenoses is more frequent in AD than in the control population (p = 0.008); (2) the average index of occlusion is greater in AD than in the control group (p < 0.00001); (3) the index of stenosis and the total number of stenoses per case are positively correlated (R = 0.67); (4) the index of stenosis correlates with the neuropathological lesions of AD and with the MMSE psychometric test; (5) the number and degree of atherosclerosis of the anterior, middle and posterior cerebral arteries is more severe in cases of AD than in the control population; (6) atherosclerosis severity is apparently associated with the severity of the vascular amyloidosis; (7) the WM rarefaction correlates with the severity of the atherosclerosis and vascular amyloidosis; (8) the total cell count and microvessel count in the areas of WM rarefaction correlate with the neuropathological lesions of AD and with the MMSE score. Our data strongly suggest that severe hemodynamic disturbances contribute to sporadic AD and support the numerous observations indicating cardiovascular system participation in the pathogenesis of these dementias.     

Treatment of vascular dementia—evidence from clinical trials with cholinesterase inhibitors

Abstract

Cerebrovascular disease (CVD), as well as secondary ischemic brain injury from cardiovascular disease, are common causes of dementia and cognitive decline in the elderly. Also, CVD frequently contributes to cognitive loss in patients with Alzheimer's disease (AD). Progress in understanding the pathogenetic mechanism involved in vascular cognitive impairment and vascular dementia (VaD) has resulted in promising treatments of these conditions. Cholinergic deficits in VaD are due to ischemia of basal forebrain nuclei and of cholinergic pathways and can be treated with the use of the cholinesterase inhibitors used in AD. Controlled clinical trials with donepezil, galantamine, and rivastigmine in VaD, as well as in patients with AD plus CVD, have demostrated improvement in cognition, behavior and activites of daily living.     

3D Assessment of Cortical Bone Porosity and Tissue Mineral Density Using High‐Resolution µCT: Effects of Resolution and Threshold Method

Current micro–computed tomography (µCT) systems allow scanning bone at resolutions capable of three‐dimensional (3D) characterization of intracortical vascular porosity and osteocyte lacunae. However, the scanning and reconstruction parameters along with the image segmentation method affect the accuracy of the measurements. In this study, the effects of scanning resolution and image threshold method in quantifying small features of cortical bone (vascular porosity, vascular canal diameter and separation, lacunar porosity and density, and tissue mineral density) were analyzed. Cortical bone from the tibia of Sprague‐Dawley rats was scanned at 1‐µm and 4‐µm resolution, reconstructions were density‐calibrated, and volumes of interest were segmented using approaches based on edge‐detection or histogram analysis. In 1‐µm resolution scans, the osteocyte lacunar spaces could be visualized, and it was possible to separate the lacunar porosity from the vascular porosity. At 4‐µm resolution, the vascular porosity and vascular canal diameter were underestimated, and osteocyte lacunae were not effectively detected, whereas the vascular canal separation and tissue mineral density were overestimated compared to 1‐µm resolution. Resolution had a much greater effect on the measurements than did threshold method, showing partial volume effects at resolutions coarser than 2 µm in two separate analyses, one of which assessed the effect of resolution on an object of known size with similar architecture to a vascular pore. Although there was little difference when using the edge‐detection versus histogram‐based threshold approaches, edge‐detection was somewhat more effective in delineating canal architecture at finer resolutions (1–2 µm). In addition, use of a high‐resolution (1 µm) density‐based threshold on lower resolution (4 µm) density‐calibrated images was not effective in improving the lower‐resolution measurements. In conclusion, if measuring cortical vascular microarchitecture, especially in small animals, a µCT resolution of 1 to 2 µm is appropriate, whereas a resolution of at least 1 µm is necessary when assessing osteocyte lacunar porosity. © 2014 American Society for Bone and Mineral Research.     

胸腹主动脉夹层动脉瘤(Stanford B型)的腔内血管外科治疗

目的 探讨Stanford B型胸腹主动脉夹层动脉瘤腔内治疗的方法。方法 对l2例StanfordB型胸腹主动脉夹层动脉瘤患者的临床资料进行回顾性研究。结果 l2例患者全为男性，年龄40～68岁，平均52．1岁。其中10例患者进行了腔内血管外科治疗，均取得了技术上的成功，术后内漏1例，3d后漏血停止。其余病例术后即时造影示瘘口已被完整覆盖，假腔无血漏入，内脏动脉等恢复真腔供血。2例未行腔内治疗的患者，l例因并发呼衰死亡，l例死于夹层动脉瘤破裂。结论对Stanford B型胸腹主动脉夹层动脉瘤的治疗，如适应证掌握合适，腔内治疗与传统的开胸手术相比，具有操作简单，损伤小，安全度大，并发症少等优点，且可大大缩短患者的住院时间。保守治疗难以控制病情的发展，易导致死亡等严重后果。