胃肠管间质瘤生物学行为相关研究新进展

胃肠管间质瘤是发生于消化管的最常见的间叶组织来源肿瘤,其生物学行为的预测成为现今研究的一大热点.本文就近年来胃肠管间质瘤生物学行为相关研究的进展情况进行综述.     

自体骨髓间质干细胞对异基因小鼠皮肤移植免疫排斥的影响

目的 观察自体骨髓间质干细胞(bone marrow stromal cells,BMSCs)对异基因小鼠皮肤移植的影响.方法 建立C57BL/6至BALB/c小鼠皮肤移植急性排斥模型,密度梯度离心法分离与贴壁法富集BALB/c小鼠BMSCs,自尾静脉输注.实验分3组,每组10只小鼠.A组:正常BALB/c小鼠+自体BMSCs,B组:仅行皮肤移植,C组:皮肤移植后BALB/c小鼠+自体BMSCs.检测各时间段皮肤组织病理表现以及相关细胞因子浓度变化.结果 由密度梯度离心法与贴壁法分离的细胞具有BMSCs的一般特征,C组较B组移植后皮肤免疫排斥反应明显减轻,IL-2、IFN-γ等细胞因子浓度在术后第7天(F=248 954.6,P＜0.05;F=148 311.7,P＜0.05)、第14天(F=117 372.3,P＜0.05:F=126 743.3,P＜0.05)均有降低.结论 异基因小鼠皮肤移植术后输注自体BMSCs可以抑制免疫排斥反应,其机制可能与减少IL-2、IFN-γ等相关细胞因子分泌有关.     

Treatment with bone marrow-derived stromal cells accelerates wound healing in diabetic rats

Bone marrow stem cells participate in tissue repair processes and may have a role in wound healing. Diabetes is characterised by delayed and poor wound healing. We investigated the potential of bone marrow-derived mesenchymal stromal cells (BMSCs) to promote healing of fascial wounds in diabetic rats. After manifestation of streptozotocin (STZ)-induced diabetic state for 5 weeks in male adult Sprague-Dawley rats, healing of fascial wounds was severely compromised. Compromised wound healing in diabetic rats was characterised by excessive polymorphonuclear cell infiltration, lack of granulation tissue formation, deficit of collagen and growth factor [transforming growth factor (TGF-beta), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), platelet-derived growth factor PDGF-BB and keratinocyte growth factor (KGF)] expression in the wound tissue and significant decrease in biomechanical strength of wounds. Treatment with BMSC systemically or locally at the wound site improved the wound-breaking strength (WBS) of fascial wounds. The improvement in WBS was associated with an immediate and significant increase in collagen levels (types I-V) in the wound bed. In addition, treatment with BMSCs increased the expression of growth factors critical to proper repair and regeneration of the damaged tissue moderately (TGF-beta, KGF) to markedly (EGF, VEGF, PDGF-BB). These data suggest that cell therapy with BMSCs has the potential to augment healing of the diabetic wounds.     

Restoration of bone defect and enhancement of bone ingrowth using partially demineralized bone matrix and marrow stromal cells

PURPOSE: This study aimed to investigate the capability of combining marrow stromal cells (MSC) and partially demineralized bone matrix (PDBM) to fill bone defect and enhance bone ingrowth using a canine non-weight-bearing gap model. METHODS: Custom-made implants with 3mm gap between the porous surface and the host bone were used. The implants were inserted into the distal femurs of 25 mongrel dogs and the gaps were randomly assigned to be filled with culture-expanded autologous MSC-loaded PDBM, autograft, fresh-frozen allograft, PDBM alone, or nothing as controls. Histomorphometry using backscattered scanning electron microscopic examination, and mechanical push-out test were performed at 6 months after surgery. RESULTS: Histomorphometry showed that amounts of bone regeneration in the gap and bone ingrowth into the porous-coated surface in the MSC-loaded PDBM-treated group were comparable to those of autograft-treated group and were significantly greater than those of allograft-treated, PDBM-treated, or non-grafted groups. Mechanical test showed the same differences. CONCLUSION: The results of this study showed that combining PDBM and autologous culture-expanded MSC restored bone stock and enhanced bone ingrowth into the porous-coated area in a canine non-weight-bearing gap model. This combination may provide an option for reconstructing bone defect when we perform a cementless revision arthroplasty.     

Repair of mandible defect with tissue engineering bone in rabbits

BACKGROUND: The aim of the present study was to investigate the effect of tissue engineering bone composed of bone marrow-derived osteoblasts and demineralized bone in repairing mandible defect. METHODS: Bone marrow-derived osteoblasts of 20 rabbits were cultured and seeded into scaffold of allogeneic demineralized bone to construct tissue engineering bone graft in vitro, which was used to repair the 10 x 5-mm bone defect made in the same rabbit mandible edge. Implant of demineralized bone alone was as the control. Rabbits were killed according to the schedule: five after 2 weeks, five after 4 weeks, five after 8 weeks, five after 12 weeks, and the implants were harvested for gross, radiographic, and histological observation. RESULTS: New bone formation at the margin region of defect and osteogenesis at the centre were observed in the implant of tissue engineering bone, and the bone formation pattern included osteogenesis, osteoconduction, and osteoinduction. In the implant of demineralized bone alone, the major bone formation pattern was 'creeping substitute'. CONCLUSIONS: The tissue engineering bone graft constructed by autogenous bone marrow-derived osteoblasts and allogeneic demineralized bone was better than demineralized bone alone in bone formation capability, which might be an ideal graft for bone defect repair.     

Mathematical Modeling of Spatio‐Temporal Dynamics of a Single Bone Multicellular Unit

During bone remodeling, bone‐resorbing osteoclasts and bone‐forming osteoblasts are organized in bone multicellular units (BMUs), which travel at a rate of 20–40 μm/d for 6–12 mo, maintaining a cylindrical structure. However, the interplay of local BMU geometry with biochemical regulation is poorly understood. We developed a mathematical model of BMU describing changes in time and space of the concentrations of proresorptive cytokine RANKL and its inhibitor osteoprotegerin (OPG), in osteoclast and osteoblast numbers, and in bone mass. We assumed that osteocytes surrounding a microfracture produce RANKL, which attracted osteoclasts. OPG and RANKL were produced by osteoblasts and diffused through bone, RANKL was eliminated by binding to OPG and RANK. Osteoblasts were coupled to osteoclasts through paracrine factors. The evolution of the BMU arising from this model was studied using numerical simulations. Our model recapitulated the spatio‐temporal dynamics observed in vivo in a cross‐section of bone. In response to a RANKL field, osteoclasts moved as a well‐confined cutting cone. The coupling of osteoclasts to osteoblasts allowed for sufficient recruitment of osteoblasts to the resorbed surfaces. The RANKL field was the highest at the microfracture in front of the BMU, whereas the OPG field peaked at the back of the BMU, resulting in the formation of a RANKL/OPG gradient, which strongly affected the rate of BMU progression and its size. Thus, the spatial organization of a BMU provides important constraints on the roles of RANKL and OPG as well as possibly other regulators in determining the outcome of remodeling in the BMU.     

十二指肠间质瘤的临床特征及外科治疗

目的探讨十二指肠间质瘤的临床特征及外科治疗效果. 方法回顾性分析我科1990～2004年14例十二指肠间质瘤的临床资料. 结果病理类型:良性2例,潜在恶性4例,恶性8例.50.0%(7/14)发生在降部,其中恶性占57.1%(4/7).临床表现为右上腹肿物(6/14),右上腹隐痛不适(5/14)和乏力、体重下降(3/14),诊断手段为十二指肠低张造影(13/14)、B超(13/14)和CT(9/14).肿瘤距离十二指肠大乳头＜3 cm或位于降部、直径≥5 cm者宜行胰十二指肠切除术,肿瘤距离十二指肠大乳头＞3 cm及较小者宜行十二指肠节段性切除术. 结论十二指肠间质瘤恶性多见,临床表现无特异性,主要依靠十二指肠低张造影、B超、CT、EUS确诊,对无远处转移的肿瘤应积极争取根治性切除.     

小肠粘膜下层的制备及细胞相容性的实验研究

目的了解猪小肠粘膜下层(SIS)的细胞相容性,探讨用SIS为生长载体复合骨髓基质干细胞(BMSCs)构筑组织工程骨的可能性。方法用物理和化学方法处理猪小肠粘膜下层,将兔骨髓基质干细胞与SIS进行体外复合培养,分别进行组织学、相差显微镜和扫描电镜观察。结果经物理和化学处理的SIS纯度高,孔隙多,胶原纤维未受损;BMSCs在SIS材料上生长、粘附、增殖,并能长入材料的孔隙内,分泌大量的细胞外基质成分。结论SIS的细胞相容性良好,不影响BMSCs的形态,对细胞生长和功能表达无抑制作用,可以用作骨组织工程的支架材料。     

脉冲电磁场影响人骨髓基质干细胞缝隙连接通讯的实验研究

目的研究脉冲电磁场(PEMFs)对人骨髓基质干细胞(hBMSCs)缝隙连接所介导细胞间通讯(GJIC)的影响。方法透射电镜观察BMSCs超微结构,应用荧光漂白恢复(FRAP)技术,通过激光共聚焦显微镜检测hBM-SCs经PEMFs刺激后GJIC的功能变化。结果经PEMFs刺激后的hBMSCs,平均荧光漂白恢复率为(64.12±0.83)%,较对照组犤(35.26±0.76)%犦有显著性增加(P<0.05)。结论PEMFs刺激能促进hBMSCs的缝隙连接通讯功能。     

骨髓基质干细胞修复兔关节软骨缺损的实验研究

目的研究以多聚乙醇酸(PGA)为支架的骨髓基质干细胞(BMSCs)复合物修复兔膝关节软骨缺损的情况。方法体外培养扩增的自体BMSCs种植于PGA支架并培养72h,然后将支架-细胞复合物植入兔关节软骨缺损模型。术后12周处死动物,标本行大体观察、组织学检查及Ⅱ型胶原免疫组化染色。结果BMSCs-PGA复合物植入后形成丰富的透明软骨样修复组织,新生软骨无明显退变。对照组主要为纤维组织及软骨下骨修复。结论BMSCs-PGA复合物可修复关节软骨缺损。