ObjectiveTo review the research progress of constructing injectable tissue engineered adipose tissue by adipose-derived stem cells (ADSCs). MethodsRecent literature about ADSCs composite three-dimensional scaffold to construct injectable tissue engineered adipose tissue is summarized, mainly on the characteristics of ADSCs, innovation of injectable scaffold, and methods to promote blood supply. ResultsADSCs have a sufficient amount and powerful ability such as secretion, excellent compatibility with injectable scaffold, plus with methods of promoting blood supply, which can build forms of injectable tissue engineered adipose tissue. ConclusionIn despite of many problems to be dealt with, ADSCs constructing injectable tissue engineered adipose tissue may provide a promising source for soft-tissue defect repair and plastic surgery.
ObjectiveTo evaluate the effect of using Schwann-like cells derived from human umbilical cord blood mesenchymal stem cells (hUCBMSCs) as the seed cells to repair large sciatic nerve defect in rats so as to provide the experimental evidence for clinical application of hUCBMSCs. MethodsFourty-five male Sprague Dawley (SD) rats in SPF grade, weighing 200-250 g, were selected. The hUCBMSCs were harvested and cultured from umbilical cord blood using lymphocyte separating and high molecular weight hydroxyethyl starch, and then was identified. The hUCBMSCs of 3rd generation were induced to Schwann-like cells, and then was identified by chemical derivatization combined with cytokine. The acellular nerve basal membrane conduit was prepared as scaffold material by the sciatic nerve of SD rats through repeated freezing, thawing, and washing. The tissue engineered nerve was prepared after 7 days of culturing Schwann-like cells (1×107 cells/mL) on the acellular nerve basal membrane conduit using the multi-point injection. The 15 mm sciatic nerve defect model was established in 30 male SD rats, which were randomly divided into 3 groups (10 rats each group). Defect was repaired with tissue engineered nerve in group A, with acellular nerve basal membrane conduit in group B, and with autologous sciatic nerve in group C. The nerve repair was evaluated through general observation, sciatic function index (SFI), nerve electrophysiology, weight of gastrocnemius muscle, and Masson staining after operation. ResultsThe hUCBMSCs showed higher expression of surface markers of mesenchymal stem cells, and Schwann-like cells showed positive expression of glia cell specific markers such as S100b, glial fibrillary acidic protein, and P75. At 8 weeks after operation, the acellular nerve basal membrane conduit had no necrosis and liquefaction, with mild adhesion, soft texture, and good continuity at nerve anastomosis site in group A; group B had similar appearance to group A; adhesion of group C was milder than that of groups A and B, with smooth anastomotic stoma and no enlargement, and the color was similar to that of normal nerve. SFI were gradually decreased, group C was significantly greater than groups A and B, group A was significantly greater than group B (P<0.05). The compound action potential could be detected in anastomotic site of 3 groups, group C was significantly greater than groups A and B, and group A was significantly greater than group B in amplitude and conduction velocity (P<0.05). Atrophy was observed in the gastrocnemius of 3 groups; wet weight's recovery rate of the gastrocnemius of group C was significantly greater than that of groups A and B, and group A was significantly greater than group B (P<0.05). Masson staining showed that large nerve fibers regeneration was found in group A, which had dense and neat arrangement with similar fiber diameter. The density and diameter of medullated fibers, thickness of myelinated axon, and axon diameter of group C were significantly greater than those of groups A and B, and group A was significantly greater than group B (P<0.05). ConclusionTissue engineered nerves from hUCBMSCs-derived Schwann-like cells can effectively repair large defects of the sciatic nerve. hUCBMSCs-derived Schwann-like cells can be used as a source of seed cells in nerve tissue engineering.
ObjectiveTo investigate the effect of cytoskeleton modification on the adipogenic differentiation of rat Achilles-derived tendon stem cells (TSCs) in vitro. MethodsTSCs were isolated from the tendon tissue of male Sprague Dawley rats (aged 3 weeks) by enzymatic digestion method and cultured for 3 passages. After the 3rd passage cells were cultured with DMEM medium containing 15% fetal bovine serum and cytochalasin D (CYD) at the concentrations of 0, 50, 100, 500, and 1 000 ng/mL, the cell survival condition and morphology changes were observed by inverted phase contrast microscope, the cytoskeleton was observed through fibrous actin (F-actin) staining, and the ratio of F-actin/soluble globular actin (G-actin) was detected and calculated through Western blot. According to the above results, the effective concentration of CYD was selected and used for next experiments. After TSCs were cultured for 3 and 7 days respectively with adipogenic induction media (induction group), adipogenic induction media containing CYD (CYD+induction group), ordinary medium (ordinary group), and ordinary medium containing CYD (CYD+ordinary group), the real-time quantitative PCR (qRT-PCR) and Western blot were carried out to measure the mRNA and protein expressions of adipogenic differentiation-related markers, including peroxisome proliferator-activated receptor γ (PPARγ), 1ipoprotein lipase (LPL), and fatty acid binding protein (aP2). ResultsThe final CYD concentration of 100 ng/mL can inhibit effectively G-actin polymerization into F-actin, but could not affect TSCs survival, which was used for next experiments. qRT-PCR and Western blot suggested that the mRNA expressions of PPARγ, LPL, and aP2 and the protein expressions of PPARγ and aP2 were increased significantly in the CYD+induction group at 3 and 7 days when compared with the induction group (P<0.05). In the CYD+ordinary group, there still was a significant increase in the mRNA expressions of PPARγ, LPL, and aP2 when compared with the ordinary group (P<0.05). ConclusionInhibition of F-actin polymerization can increase adipogenic differentiation of rat Achilles-derived TSCs in vitro, and cytoskeleton modification is a pre-requisite for TSCs differentiation into adipocytes, which might have important implications for the mechanism research of tendinopathy.
Pulmonary arterial hypertension is a kind of intractable disease which threatens human health severely. The results of operation are unsatisfactory. Clinical drug therapy is the major treatment which aims to relieve symptoms, improve the quality of life, and prevent the disease from progressing. Over the last several years, the studies of stem cells provide a new direction for the treatment of pulmonary arterial hypertension. It's demonstrated that the therapeutic effects of stem cells are better than that of the traditional methods. With the deepening of the researches, the therapy of stem cells is more and more compelling. The therapy of stem cells for pulmonary arterial hypertension is reviewed in this paper.
Objective To systematically review the effectiveness and safety of autologous implantation of stem cells for diabetic peripheral neuropathy (DPN). Methods Randomized controlled trials on relevant studies were retrieved in databases including CBM (1978-2011.6), CNKI (1979-2011.6), MEDLINE (1950-2011.6), PubMed (1950-2011.6), EMbase (1970-2011.6) and The Cochrane Library (Issue 3, 2011). References of the included studies were also retrieved. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assess the methodological quality of the included studies. Then, meta-analysis was performed using RevMan 5.0 software.Results Four RCTs involving 68 patients (136 limbs) were included, most of which were low in methodological quality. The results of meta-analysis indicated that, autologous stem cell therapy improved or even eliminated DPN symptoms including pain, numbness, and cold sensation in the limbs, intermittent limping, and rest pain. Compared with the routine therapy, autologous stem cell therapy improved tibial sensory nerve conduction velocity (MD=5.75, 95%CI 3.86 to 7.64, Plt;0.000 01), tibial motor nerve conduction velocity (MD=4.04, 95%CI 0.90 to 7.18, P=0.001), sural sensory nerve conduction velocity (MD=7.47, 95%CI 4.00 to 10.94, Plt;0.000 1), and sural motor nerve conduction velocity (MD=3.38, 95%CI 0.07 to 7.58, P=0.05), with no adverse reaction reported. Conclusion Current evidence shows that, autologous stem cell therapy is effective in treating DPN. Due to the lack of high quality studies, more high quality RCTs are needed to verify the above conclusion.
Objective To assess the effectiveness and safety of high-dose chemotherapy assisted with autologous peripheral blood stem cell treatment (APBSCT+HDC) for small cell lung cancer (SCLC). Methods The databases such as MEDLINE (1970 to January 2011), EMBASE (1980 to January 2011), Science Direct (1980 to January 2011), The Cochrane Library (Issue 3, 2010), CNKI (from the date of establishment to December 2010), CBM (from the date of establishment to December 2010) and Wanfang database (from the date of establishment to December 2010) were searched for collecting randomized controlled trials (RCTs) on APBSCT+HDC for SCLC. According to the inclusive and exclusive criteria, the trials were screened, the data were extracted, the methodological quality was assessed, and then Meta-analysis was conducted by using RevMan 5.0 software. Results A total of 6 RCTs involving 737 patients with SCLC were included. The results of Meta-analyses were as follows: the APBSCT+HDC for SCLC was significantly superior to the conventional chemotherapy in the total effective rate (RR=1.14, 95%CI 1.07 to 1.21, Plt;0.000 1) and the overall survival rate (RR=3.74, 95%CI 2.13 to 6.58, Plt;0.000 01), and it was superior in reducing the incidence of III/IV grade red blood cell reduction (RR=1.97, 95%CI 1.15 to 3.38, P=0.01) and thrombopenia (RR=1.93, 95%CI 1.06 to 3.54, P=0.03) with significant differences; but there was no significant difference between the two groups in reducing the incidence of III/IV leukopenia. Conclusions Compared with the conventional chemotherapy, APBSCT+HDC treatment for SCLC can improve the overall effective rate and overall survival rate, but it can also increase the risks of severe hematologic toxic reaction. Because of the small scale and low quality of the included studies, this conclusion still needs to be confirmed by high-quality, large-scale and multi-centered RCTs.
【摘要】 目的 探讨自体造血干细胞移植（autologous hematopoietic stem cell transplantation，auto-HSCT）治疗侵袭性NK/T细胞淋巴瘤的疗效。 方法 对我科2005年1月16日收治的1例侵袭性NK/T细胞淋巴瘤患者的造血干细胞移植和随访资料进行回顾性分析，并复习国内外相关文献。 结果 患者为37岁女性，诊断结外鼻型NK/T细胞淋巴瘤，系统性，经CHOAP和ICE方案化学疗法、手术、局部放射治疗控制病情良好后，采集自体骨髓造血干细胞，行auto-HSCT，预处理方案为全身放射治疗+ECy；移植+29 d造血功能即顺利重建；移植后密切随访，患者一直处于完全缓解，至今已存活67个月。 结论 auto-HSCT治疗侵袭性NK/T细胞淋巴瘤疗效肯定、可靠。【Abstract】 Objective To explore the therapeutic effect of autologous hematopoietic stem cell transplantation (auto-HSCT) on aggressive NK/T lymphoma. Methods The clinical data of one patient with aggressive NK/T lymphoma diagnosed in January 2005 were retrospectively analyzed, and the relevant domestic literatures were analyzed. Results This thirty-seven-year-old female patient had good disease control after undergoing chemotherapy with CHOAP and ICE regimens, surgery, and locoregional radiotherapy. After that, she had been collected enough bone marrow-derived hematopoietic stem cells, then underwent auto-HSCT with these cells. The conditioning regimen was TBI plus ECy. On the +29th day after transplantation,the hematopoietic reconstruction was successful. During the follow-up period, the patient was in complete remission status all along and her disease-free survival (DFS) was 67 months. Conclusion Auto-HSCT is effective on aggressive NK/T lymphoma.
【摘要】 目的 分析异基因造血干细胞移植术（allogeneic hematopoietic stem cell transplantation，allo-HSCT）后并发毛细血管渗漏综合征（capillary leak syndrome，CLS）的发生率、危险因素和结局，并探讨其防治措施。 方法 回顾性分析2005年6月-2011年2月住院的allo-HSCT术后14例并发CLS的临床资料。 结果 CLS发生率为9.2%（14/152）。年龄、性别、诊断、HLA配型、预处理、CD34+细胞量、粒细胞集落刺激因子（granulocyte colony-stimulating factor，G-CSF）用量、植入时间均不能认定为造血干细胞移植后CLS诱发因素。 结论 HSCT术后CLS诱因尚不清楚，采用限水、减量G-CSF、使用糖皮质激素和羟乙基淀粉等措施及时治疗，有助于控制CLS。【Abstract】 Objective To study the occurrence rate, risk factors and outcomes of capillary leak syndrome (CLS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and discuss its prevention and treatment. Methods We retrospectively analyzed the clinical records of 14 allo-HSCT recipients complicated with CLS from June 2005 to February 2011. Results Fourteen out of 152 patients developed CLS with a cumulative incidence of 9.2 %. None of the 8 clinical parameters including age, gender, underlying disease, donor type, conditioning regimen, CD34+ cell dose, granulocyte colony-stimulating factor (G-CSF) dosage, and days to neutrophil engraftment could be identified as risk factors for the occurrence of CLS. Conclusions Risk factors for CLS after allo-HSCT have not been fully established. Restriction of water intake, administration of corticosteroids and hydroxyethyl starch can be beneficial for patients with CLS.
【摘要】 目的 分析异基因造血干细胞移植术（allogeneic hematopoietic stem cell transplantation，allo-HSCT）后出血性膀胱炎（hemorrhagic cystitis，HC）相关的危险因素，动态监测受者尿BK病毒（BK virus，BKV），分析其与HC发病的关系。 方法 回顾性分析2003年3月-2008年1月期间接受allo-HSCT的121例患者的资料，选择8个临床参数[年龄、性别、疾病类型、移植时疾病状态、供者类型、预处理方案、急性移植物抗宿主病（acute graft-versus-host disease，aGVHD）、aGVHD的预防方案]作COX回归分析。采用SYBR Green染料实时荧光定量聚合酶链反应法对2006年9月-2008年1月42例allo-HSCT患者尿BKV载量进行动态监测，分析被检查者尿液BKV基因载量与HC发生以及严重程度的关系。 结果 121例患者中有24例发生HC，发病时间为术后0~63 d，中位时间40 d；持续时间7~150 d，中位时间22 d。Ⅱ~Ⅳ度aGVHD为HC的独立危险因素[RR=8.304，95%CI（1.223，56.396），P=0.030]。allo-HSCT受者尿液中BKV检出率为100%（42/42）。与正常人及未发生HC的allo-HSCT受者相比，HC患者尿中BKV基因载量具有更高平均峰值。 结论 Ⅱ~Ⅳ度aGVHD，尿中BKV DNA高载量与HC的发生有相关性。【Abstract】 Objective To identify the risk factors for hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and define the quantitative relationship between BK virus (BKV) DNA load with HC. Methods The medical records of 121 patients undergoing allo-HSCT from March 2003 to January 2008 were retrospectively analyzed. Eight clinical parameters were selected for COX regression analysis, including age, sex, underlying disease, disease status at transplant, donor type, conditioning regimen, acute graft-versus-host disease (aGVHD), and GVHD prophylaxis. From September 2006 to January 2008, mid-stream urine samples were continuously collected from 42 patients with allo-HSCT. SYBR green real-time polymerase chain reaction, technique was utilized to define the quantitative relationship between BKV DNA load and HC. Results Twenty-four out of 121 patients developed HC. The median time of onset was 40 days after HSCT, ranged from 0 to 63 days. The disease lasted for 7 to 150 days, with a median duration of 22 days. Grade Ⅱ-Ⅳ aGVHD [RR=8.304, 95% CI (1.223,56.396); P=0.030] was identified as an independent risk factor for the occurrence of HC. BKV excretion was detected in 100% (42/42) of the recipients of allo-HSCT. When compared with asymptomatic patients and allo-HSCT recipients without HC, patients with HC had a significantly higher mean peak BKV DNA load. Conclusions Patients are at an increased risk of developing HC if they have grade Ⅱ-Ⅳ aGVHD. A correlation between the load of BKV and incidence of HC may exist.
【摘要】 目的 探讨对自体造血干细胞移植（autologous hematopoietic stem cell transplantation，auto-HSCT）后复发的非霍奇金淋巴瘤患者再进行异基因造血干细胞移植（allogeneic hematopoietic stem cell transplantation，allo-HSCT）治疗的临床疗效。 方法 收集2000年1月-2010年12月难治性恶性淋巴瘤采用auto-HSCT后复发患者11例，病程27个月~6.5年。所有患者在auto-HSCT前均为复发难治性病例，auto-HSCT后，完全缓解8例，部分缓解3例，自体移植后中位复发时间15个月，患者复发后采用异基因亲缘造血干细胞移植，人类白细胞抗原（human leukocyte antigen，HLA）全相合（6/6）6例，5/6相合3例，4/6相合2例；性别相同6例，性别不同5例。预处理方案为FBC方案，即氟达拉滨30 mg/m2 1~5 d，白消安12~14 mg/kg分4 d口服，环磷酰胺120 mg/kg分2 d使用。移植物均为外周血造血干细胞加骨髓。移植物抗宿主病（graft-versus-host disease，GVHD）的预防：HLA全相合采用环孢素+短程甲氨蝶呤+吗替麦考酚酯，不全相合采用抗胸腺细胞球蛋白+环孢素+短程甲氨蝶呤+吗替麦考酚酯。 结果 11例患者全部获得造血重建，急性GVHD发生6例（54.55%），其中Ⅰ度、Ⅱ度4例，Ⅲ度、Ⅳ度各1例；1例Ⅳ度GVHD因合并感染死亡，5例均得到有效控制；发生慢性GVHD 7例（63.64%），其中有2例急性GVHD转为慢性，4例局限型，3例广泛型。随访8个月~9年，有4例分别于移植后8、15、21、34个月疾病复发，另外6例仍生存。 结论 allo-HSCT对于auto-HSCT后复发的非霍奇金淋巴瘤患者仍是一种有效的挽救性治疗手段。【Abstract】 Objective To explore the clinical efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on relapsing non-Hodgkin′s lymphoma after autologous stem cell transplantation (auto-HSCT). Methods The clinical data of 11 patients with recurrent non-Hodgkin′s lymphoma after auto-HSCT from January 2000 to December 2010 were collected, including nine males and 2 females with the median age of 39 years (13-48 years old), and the median duration of the disease was 3 years (27 months-6.5 years). All patients were relapsed or refractory cases. After auto-HSCT, complete remission was found in 8 and partial remission was in 3. The recurrence median time after auto-HSCT was 15 months. The patients underwent allo-HSCT after the recurrence of the disease. In the 11 patients, human leukocyte antigen (HLA) full matched (6/6) in 6, 5/6 matched in 3, and 4/6 matched in 2; the same gender in 6 and different gender in 5. FBC conditioning regimen: fludarabine 30 mg/m2 for 1-5 days, BU 12-14 mg/kg in 4 days of oral, CY 120 mg/kg in 2 days. Grafts are peripheral blood stem cells plus bone marrow. Prevention of graft-versus-host disease (GVHD): HLA full-matched by CsA+short-term MTX+MMF and mismatched by ATG+CsA+short-term MTX+MMF. Results All of the 11 patients received hematopoietic reconstruction, acute GVHD occurred in 6 cases (54.55%), including degree Ⅰ plus Ⅱ in 4, degree Ⅲ in 1 and degree Ⅳ in 1. One patient died of infection due to degree Ⅳ GVHD, and the rest had been effectively controlled. Chronic GVHD occurred in 7 patients (63.64%); limited type was in 4 in and extensive type was in 3. During the follow-up period of 8 months-9 years, 4 patients relapsed 8, 15, 21, and 34 months after transplantation, and the other 6 patients was still alive. Conclusion Allo-HSCT is effective on relapsing non-Hodgkin′s lymphoma after auto-HSCT.