间充质干细胞的来源

目的:间充质干细胞具有强大的增殖能力和多向分化潜能,文章对其主要的来源途径予以综述。资料来源:应用计算机检索Medline1991-01/2006-01期间的相关文章,检索词为“mesenchyma stem cells,origin,research progress”,并限定文章语言种类为English。同时计算机检索中国期刊全文数据库1998-01/2006-10期间的相关文章,检索词为“间充质干细胞,来源,研究进展”,并限定文章语言种类为中文。资料选择:对资料进行初审,并查看每篇文献后的引文。纳入标准:①间充质干细胞的起源。②间充质干细胞研究进展、干细胞的分离及鉴定。排除标准:重复研究、个案报告或Meta分析类文章。资料提炼:共收集到96篇相关文献,40篇文献符合纳入标准,排除的56篇文献为内容陈旧或重复。符合纳入标准的40篇文献中,分别涉及骨髓、肌肉、脐血、胎盘、外周血、脂肪组织、血管及其他来源的间充质干细胞。资料综合:间充质干细胞是属于中胚层的一类多能干细胞,具有强大的增殖能力和多向分化潜能,动物模型试验和临床应用研究也取得了一定的效果。间充质干细胞来源广泛,易于获得,临床上为神经损伤及其他系统的损伤修复提供了更为广泛的途径。结论:间充质干细胞主要来源于骨髓、肌肉、脐血、外周血、胎盘等组织,具有广阔的应用前景。     

Allogeneic bone marrow transplantation for chronic myeloid leukemia in first chronic phase: a randomized trial of busulfan-cytoxan versus cytoxan-total body irradiation as preparative regimen: a report from the French Society of Bone Marrow Graft (SFGM)

From March 1988 to March 1991, 19 French bone marrow transplant (BMT) centers participated in a prospective randomized trial comparing two conditioning regimens for patients with chronic myeloid leukemia transplanted in first chronic phase with an HLA identical sibling donor. A total of 120 consecutive patients were randomized to receive either 120 mg/kg of cyclophosphamide followed by total body irradiation (CY-TBI; n = 55) or 16 mg/kg of busulfan followed by 120 mg/kg of CY (BU-CY; n = 65). Two different TBI regimens were used. Thirteen patients received a 10-Gy single-dose TBI (SDTBI), and 42 received a fractionated TBI (FTBI). Median time between diagnosis and BMT was 315 days. Overall 5-year actuarial survival was 62.9% (65.8% +/- 12.5% for CY-TBI and 60.6 +/- 11.7% for BU-CY; P = .5), and overall disease-free survival was 55% (51% +/- 14% for CY-TBI and 59.1% +/- 11.8% for BU-CY; P = .75). All patients conditioned with CY-TBI experienced sustained engraftment; in contrast, 4 of 65 patients conditioned with BU-CY rejected the graft (P = .18). There was no significant statistical difference between the two groups regarding transplant-related mortality (29% for CY-TBI and 38% for BU-CY; P = .44). So far, with a median follow up of 42 months, 11 patients have relapsed; 9 relapses occurred after CY-TBI, mostly after FTBI (8 of 9) and 2 after BU-CY (P = .02). The actuarial risk of relapse was 4.4% +/- 6.7% after BU-CY, 11.1% +/- 20.8% after SDTBI, and 31.3% +/- 18.1% after FTBI (P = .039). In addition, independently of the conditioning regimen, the increase of posttransplant immunosuppression in 16 patients with an anti- interleukin-2 receptor monoclonal antibody (MoAb) in addition to a short course of methotrexate and cyclosporine was shown to increase the actuarial risk of relapse (57% +/- 30% with MoAb v 9% +/- 7.3% without MoAb; P = .001). We conclude that BU is an acceptable alternative to TBI for patients with chronic myeloid leukemia in first chronic phase receiving BMT from HLA identical sibling donors. Both BU-CY and CY-TBI regimens gave similar transplant-related mortality, and the antileukemic efficiency of BU-CY regimen was either similar or even higher than that of CY-TBI.     

Extracellular phosphorylation converts pigment epithelium-derived factor from a neurotrophic to an antiangiogenic factor

The pigment epithelium-derived factor (PEDF) belongs to the superfamily of serine protease inhibitors (serpin). There have been 2 distinct functions attributed to this factor, which can act either as a neurotrophic or as an antiangiogenic factor. Besides its localization in the eye, PEDF was recently reported to be present also in human plasma. We found that PEDF purified from plasma is a phosphoprotein, which is extracellularly phosphorylated by protein kinase CK2 (CK2) and to a lesser degree, intracellularly, by protein kinase A (PKA). CK2 phosphorylates PEDF on 2 main residues, Ser24 and Ser114, and PKA phosphorylates PEDF on one residue only, Ser227. The physiologic relevance of these phosphorylations was determined using phosphorylation site mutants. We found that both CK2 and PKA phosphorylations of PEDF markedly affect its physiologic function. The fully CK2 phosphorylation site mutant S24, 114E abolished PEDF neurotrophic activity but enhanced its antiangiogenic activity, while the PKA phosphorylation site mutant S227E reduced PEDF antiangiogenic activity. This is a novel role of extracellular phosphorylation that is shown here to completely change the nature of PEDF from a neutrophic to an antiangiogenic factor.     

Gene therapy of chronic granulomatous disease

Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder which results from absence or malfunction of the respiratory burst oxidase normally expressed in neutrophils and other phagocytic leukocytes. Two-thirds of the patients are males hemizygous for mutations in the X-linked gene coding for gp91-phox. As a therapeutic approach towards the X-linked form of CGD bicistronic retroviral vectors containing the gp91-phox gene and a selectable marker gene were constructed. The ability of these vectors to restore NADPH oxidase activity was tested in a human myeloid leukemic cell line that is defective in superoxide production, as well as in primary CD34+ cells obtained from X-CGD patients. Under optimal conditions 80% of the CD34+ cells derived from bone marrow of one X-CGD patient were transduced. The level of superoxide production, in phagocytes derived from transduced cells was 68.9% of normal levels. Considering that low levels of superoxide generating activity are sufficient for normal host defense, the present experiments provide the basis for the development of a gene replacement therapy for the X-linked form of CGD.     

Coexistent Mahaim and Kent accessory connections: diagnostic and therapeutic implications

Six patients with coexistent Mahaim and Kent accessory connections are described. Two had left nodoventricular Mahaim connections, the first reported cases demonstrating these findings. In neither were the left-sided Mahaim connections components of a tachycardia and their presence was incidental. In two of four with nodoventricular connections, associated atrioventricular (AV) node conduction and coexistent posteroseptal accessory pathways were found. One of these had the unusual finding of a right-sided Mahaim connection arising from a "fast" AV node pathway. In only one patient did the tachycardia incorporate the Mahaim connection. In this patient, anterograde conduction during tachycardia occurred over a right nodoventricular connection whereas retrograde conduction occurred through a concealed right free wall Kent connection. Two patients had fasciculoventricular connections that were associated with either septal (one patient) or left free wall (one patient) Kent connections. The latter also had evidence of enhanced AV node conduction. This report is unique in that it describes in detail two patients with left nodoventricular connections (Mahaim) inserting in or near the left posterior fascicle. Combined Kent and Mahaim connections, present in the six patients, appear to occur in approximately 5% of patients with the Wolff-Parkinson-White syndrome. Precise identification of bypass connections critical for reentrant circuits is essential for intelligent application of treatment options.     

Bone marrow transplantation with unrelated donors: what is the probability of identifying an HLA-A/B/Cw/DRB1/B3/B5/DQB1-matched donor?

Patients transplanted with marrow from an HLA-ABDR serologically matched unrelated donor suffer from more post-transplant complications than those who are transplanted with marrow from an HLA-identical sibling. This is most likely due to either HLA-ABDR incompatibilities not resolved by standard techniques and/or HLA polymorphisms not tested for by routine tissue typing (HLA-Cw,-DQ). By resolving these incompatibilities by molecular techniques combined with the in vitro cytotoxic T lymphocyte precursor frequency (CTLpf) test, we have shown that a high degree of HLA compatibility is associated with increased patient survival. However, higher requirements for HLA matching decrease the number of available donors. We have estimated the probability of finding an HLA-A/B/Cw/DRB1/DRB3/DRB5/DQB1 compatible donor based on 104 consecutive unrelated bone marrow donor searches initiated between January 1995 and December 1997, with December 1998 as the endpoint. For 96 patients (92.3%), one or more ABDR-identical donors were listed in the Bone Marrow Donor Worldwide Registry (BMDW). After contacting the registries, we obtained at least one (mean, 5.36; range, 1-20; total, 461) blood sample for 86 patients. A highly compatible donor was identified for 33/86 patients (38.4%), after testing an average number of 4.5 donors/patients (range, 1-13). However, by accepting an HLA-DRB3 or -DQB1 or -Cw incompatibility, this number would be as high as 68.6%. Approximately half of the patients (n = 40) for whom a search had been initiated have been transplanted: 22 patients with a perfectly matched donor, 15 patients with an HLA-DRB3 or -DQB1 or -Cw mismatch and three with other mismatches. The average time needed to identify the most compatible donor was 4 months. Extremely long searches seemed to be less useful, because after testing the first seven, a more compatible donor was seldom found. These results show that even when requirements for compatibility are high, the chances of finding a donor remain considerably low.     

Improved glucose tolerance in acyl CoA:diacylglycerol acyltransferase 1-null mice is dependent on diet

Background  

Mice that lack acyl CoA:diacylglycerol acyltransferase (Dgat1 ^-/- mice) are reported to have a reduced body fat content and improved glucose tolerance and insulin sensitivity. Studies so far have focussed on male null mice fed a high fat diet and there are few data on heterozygotes. We compared male and female Dgat1 ^-/-, Dgat1 ^+/- and Dgat1 ^+/+ C57Bl/6 mice fed on either standard chow or a high fat diet.     

Arthroscopic management of lateral meniscal cysts

This study presents seven cases of lateral meniscal cysts treated arthroscopically. All were noted to have meniscal lesions at the time of surgery; there were five flap tears and two radial tears. Partial arthroscopic meniscectomy was performed and the contents of the cysts were manipulated into the joint in six of seven cases. One patient underwent open cyst excision in addition to partial arthroscopic meniscectomy. Followup ranged from 18 months to 4 years with an average of 28 months. There were no cyst recurrences. The pathologic basis of the meniscal cyst is controversial, but recent work suggests the etiology is infiltration of joint fluid through micro and macro tears in the meniscus. Partial meniscectomy retains valuable meniscal function while minimizing the likelihood of cyst reformation. We found arthroscopic partial meniscectomy with manipulation of the contents of the cyst into the joint to be a successful alternative to complete open meniscectomy.