Engrafted bone marrow-derived flk-(1+) mesenchymal stem cells regenerate skin tissue

Stem cell plasticity has created great interest because of its potential therapeutic application in degenerative or inherited diseases. Transplantation of bone marrow-derived stem cells was shown to give rise to cells of muscle, liver, nerve, endothelium, epithelium, and so on. But there are still disputes about stem cell plasticity, especially concerning the contribution of bone marrow-derived cells to skin cells. In this study, CM-DiI fluorescence-labeled Flk-(1+) bone marrow mesenchymal stem cells (bMSCs) of BALB/c mice (H-2Kd, white) were transplanted into lethally irradiated C57BL/6 mice (H-2Kb, black). By fluorescence tracing, we found that donor cells could migrate and take residency at the skin, which was confirmed by Y chromosome-specific PCR and Southern blot. The recipient mice grew white hairs about 40 days later and white hairs could spread over the body. Immunochemistry staining and RT-PCR demonstrated that skin tissue within the white hair regions was largely composed of donor-derived H-2Kd cells, including stem cells and committed cells. Furthermore, most skin cells cultured from white hair skin originated from the donor. Thus, our findings provide direct evidence that bone marrow-derived cells can give rise to functional skin cells and regenerate skin tissue. These may have important scientific implications in stem cell biology and transplantation therapy for skin tissue injury.     

经皮肾动脉成形术治疗肾动脉狭窄的现状

随着诊断手段和经皮介入治疗器械的进步,近10年来,经皮肾动脉成形术治疗肾动脉狭窄发展迅速,其适应证不断扩大,但什么样患者需要接受介入治疗、是否所有介入治疗均能改善血压和肾功能,目前尚存在一定争议。现在我们国内有许多心脏介入医师往往在冠状动脉造影术中做个“顺路”肾     

CCR2 expression by brain microvascular endothelial cells is critical for macrophage transendothelial migration in response to CCL2

While the expression of chemokine receptors by endothelial cells is now well established, little is known of the function of these receptors at this cellular locale. However, given that chemokines are instrumental in directing leukocytes to specific parenchymal sites, one possibility is that endothelial chemokine receptors play a role in the process of leukocyte extravasation. To test this hypothesis, we investigated the contribution of CCR2, the major cognate receptor for the chemokine CCL2 (formerly known as MCP-1), to CCL2-stimulated transendothelial migration of macrophages (m?) across cultured brain microvascular endothelial cells (BMEC). Specifically, we prepared both BMEC and m? from wild-type (WT) mice and mice deficient in CCR2; i.e., CCR2 (-/-), and compared the ability of WT and CCR2 (-/-) BMEC to support CCL2-stimulated transendothelial migration of WT and CCR2 (-/-) m?. In response to CCL2, WT m?, but not CCR2 (-/-) m?, were stimulated to migrate across WT BMEC, consistent with the recognized obligatory role for CCR2 in mediating CCL2-stimulated responses. Remarkably, however, neither WT nor CCR2 (-/-) m? were stimulated by CCL2 to migrate across CCR2 (-/-) BMEC. In contrast, both types of m? were able to migrate similarly across both types of BMEC in response to another chemokine--CCL3 (formerly known as MIP-1alpha)--which utilizes receptors other than CCR2. Lastly, CCL2-induced m? transendothelial migration was blocked by treatment of WT BMEC with pertussis toxin, suggesting that CCR2 is functionally coupled to the inhibitory G protein Galphai, much as it is in other cell types. These results highlight a heretofore-unrecognized role for endothelial CCR2 in mediating transendothelial migration.     

Where is the blood–brain barrier … really?

Few terms in the biomedical lexicon are as widely recognized as the phrase blood-brain barrier (BBB). Indeed, it immediately conjures up a "barricade" between the blood and the brain, a feature often considered more obstacle than safeguard. In truth, the BBB performs in both capacities, and it is precisely this duality that imparts such a vital role to the BBB in influencing physiological and pathophysiological processes in the CNS. Although the concept is more than a century old, the BBB continues to remain enigmatic in both substance and idea, with seemingly resolved issues once again beckoning for clarification. In this regard, recent technological advancements, such as sequencing of the human genome and development of microarray analysis, have illuminated novel aspects of vascular gene expression and provoked reconsideration of the cellular and biochemical makeup of the BBB. In light of the critical impact of the BBB in the realms of science and medicine, this Mini-Review will revisit the topic of the composition of the BBB, specifically highlighting how recent developments in endothelial biology have prompted a reevaluation of its precise vascular location. We have intentionally avoided discussing generalized features of the BBB, as these have been skillfully described elsewhere as noted.     

Response of human islets to isolation stress and the effect of antioxidant treatment

The process of human islet isolation triggers a cascade of stressful events in the islets of Langerhans involving activation of apoptosis and necrosis and the production of proinflammatory molecules that negatively influence islet yield and function and may produce detrimental effects after islet transplantation. In this study, we showed that activation of nuclear factor-kappaB (NF-kappaB) and poly(ADP-ribose) polymerase (PARP), two of the major pathways responsible for cellular responses to stress, already occurs in pancreatic cells during the isolation procedure. NF-kappaB-dependent reactions, such as production and release of interleukin-6 and -8 and macrophage chemoattractant protein 1, were observed days after the isolation procedure in isolated purified islets. Under culture conditions specially designed to mimic isolation stress, islet proinflammatory responses were even more pronounced and correlated with higher islet cell loss and impaired secretory function. Here we present novel evidence that early interventions aimed at reducing oxidative stress of pancreatic cells and islets through the use of the catalytic antioxidant probe AEOL10150 (manganese [III] 5,10,15,20-tetrakis [1,3,-diethyl-2imidazoyl] manganese-porphyrin pentachloride [TDE-2,5-IP]) effectively reduces NF-kappaB binding to DNA, the release of cytokines and chemokines, and PARP activation in islet cells, resulting in higher survival and better insulin release. These findings support the concept that the isolation process predisposes islets to subsequent damage and functional impairment. Blocking oxidative stress can be beneficial in reducing islet vulnerability and can potentially have a significant impact on transplantation outcome.     

成人及家兔阴茎海绵体平滑肌细胞培养和鉴定

目的 :探索阴茎海绵体平滑肌细胞 (CCSM)体外培养及鉴定方法。　方法 :采用勃起功能正常的成年男子及新西兰家兔的新鲜阴茎标本 ,经处理后采用原代细胞培养法 ,对阴茎海绵体组织块进行培养 ,获得CCSM后用光镜、透射电镜和免疫组化等多种方法从细胞形态学及CCSM生长特性等不同侧面对培养的人及新西兰家兔的CCSM进行鉴定 ,并测定CCSM在体外培养时的细胞增殖情况。　结果 :经 2 4h潜伏期 ,体外培养的CCSM进入指数增长期 ,维持约 96h后进入平台期 ;从接种组织块至长成单层细胞约需 15～ 2 0d ,传代后约 4～ 7d后长成单层 ;传代后的细胞增殖旺盛 ,成束状生长 ,并呈现层叠排列及“峰 谷”现象 ;CCSM在体外可稳定传 7～ 12代 ,传代期间其形态及增殖活性变化不明显 ;各种检测鉴定均证实所获细胞为CCSM。　结论 :CCSM原代细胞培养法简便、稳定、可靠 ,对研究阴茎的勃起机制及勃起功能障碍的发生、发展、调控及其治疗药物筛选有重要理论及现实意义。