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Adult mesenchymal stem cells and their potency in the cell-based therapy. 成体间充质干细胞及其在细胞治疗中的作用。
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2013-01-01
Madhurima Das, Inger Birgitta Sundell, Prasad S Koka

Recent advances in the field of regenerative medicines manifested the unique properties of stem cells including the ability of self-renewal and differentiation to make them available for their replacement in tissue injury. Mesenchymal stem cells (MSCs) are important tools in treating immune disorders and in tissue repair due to their multipotency, immunosuppressive properties, and production of cytokines or growth factors. MSC-mediated therapy is a fast-growing field that has proven safe and effective in the treatment of various degenerative diseases and tissue injuries. Generation of induced pluripotent stem (iPS) cells holds a great promise for regenerative medicine and other aspects of clinical applications. The mechanisms governing multipotency in MSCs are not well understood. This review mainly throws light on the biology of MSCs, including their efficiency in treating several diseases and also the progress of the use of iPSC-derived MSC widely in the clinic.

再生医学领域的最新进展表明干细胞的独特特性,包括自我更新和分化的能力,使它们可以在组织损伤中替代。间充质干细胞(MSCs)由于其多能性、免疫抑制特性和产生细胞因子或生长因子而成为治疗免疫疾病和组织修复的重要工具。msc介导的治疗是一个快速发展的领域,在治疗各种退行性疾病和组织损伤方面已被证明是安全有效的。诱导多能干细胞的产生在再生医学和其他临床应用方面具有很大的前景。控制MSCs多能性的机制尚不清楚。本文主要综述了间充质干细胞的生物学特性,包括其治疗多种疾病的功效,以及ipsc衍生的间充质干细胞在临床中的广泛应用进展。
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引用次数: 0
Nodal, Nanog, DAZL and SMAD gene expression in human amniotic fluid stem cells. Nodal、Nanog、DAZL和SMAD基因在人羊水干细胞中的表达。
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2013-01-01
Konstantinos Stefanidis, Vasileios Pergialiotis, Dimitrios Christakis, Dimitrios Loutradis, Aristides Antsaklis

The aim of this study was to investigate the expression of Nodal (NODAL Homolog (mouse), Nanog (Nanog Homeobox), DAZL (Deleted in Azoospermia Like) and SMAD (SMAD Family member) genes and their potential role in the regulation of self-renewal in human amniotic fluid-derived stem cells. In this experimental study human amniotic fluid-derived stem cells were analyzed for messenger RNA expression of Nodal. Immunocytochemistry also was performed to determine Nanog and DAZL. SMAD genes expression analysis was performed using cDNA Microarray analysis. Nodal mRNA was positively expressed in all samples of amniotic fluid derived stem cells. Amniotic fluid-derived stem cells showed strong immunoreactivity for molecular markers of undifferentiated human embryonic stem cells including Nanog and DAZL. Among the 8 SMAD genes expressions analyzed SMAD1, SMAD2, SMAD3, SMAD4 and SMAD7 showed positive expression. In conclusion amniotic fluid-derived stem cells seem to express Nodal, Nanog and DAZL and it speculated that the regulation of self-renewal in AFSc could be similar as in human embryonic stem cells.

本研究的目的是研究Nodal(小鼠)、Nanog (Nanog Homeobox)、DAZL (Deleted in Azoospermia Like)和SMAD (SMAD家族成员)基因的表达及其在人羊水来源干细胞自我更新调控中的潜在作用。本实验研究分析了人羊水干细胞中Nodal信使RNA的表达。免疫细胞化学检测Nanog和DAZL。采用cDNA Microarray分析SMAD基因表达。在所有羊水干细胞样本中,淋巴结mRNA均呈阳性表达。羊水干细胞对Nanog和DAZL等未分化人胚胎干细胞分子标记具有较强的免疫反应性。在分析的8个SMAD基因表达中,SMAD1、SMAD2、SMAD3、SMAD4和SMAD7表达阳性。综上所述,羊水干细胞似乎表达Nodal、Nanog和DAZL,推测AFSc中自我更新的调控可能与人类胚胎干细胞相似。
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引用次数: 0
Regenerative potential of dental pulp mesenchymal stem cells harvested from high caries patient's teeth. 高龋患者牙髓间充质干细胞的再生潜力。
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2013-01-01
Ramesh Rajendran, Sushruth Gopal, Huda Masood, Purushottam Vivek, Kaushik Deb

Dental pulp are known to contains stem cells or dentinogenic progenitors that are responsible for dentin repair. Dental pulp Stem cells from Human Exfoliated Deciduous teeth (SHED) represent a population of postnatal stem cells capable of extensive proliferation and multipotential or multilineage differentiations. This potential for tissue regeneration has become the current basis for dental pulp stem cell banking. Here, we have attempted to develop a protocol for harvesting stem cells from patients with High Caries tooth, which are most often electively discarded. We have characterized the stem cells with mesenchymal stem cell markers and have compared their potential to grow in culture, doubling times, and differentiate into different lineages, with normal bone marrow mesenchymal stem cells (MSCs). We observed that the MSCs from dental pulp grew faster, with lower doubling time, and had equal efficiency in differentiating to various lineages, when subjected to standard directed differentiation protocols. This paper establishes that discarded High Carries Tooth can be a good source for regenerative medicine and also could be a potential source for MSCs and dental pulp MSC banking.

众所周知,牙髓中含有负责修复牙本质的干细胞或牙本质原体细胞。人脱落乳牙(SHED)牙髓干细胞是一种具有广泛增殖和多潜能或多谱系分化能力的产后干细胞。这种组织再生的潜力已成为当前牙髓干细胞库的基础。在这里,我们试图开发一种从高龋病患者的牙齿中收集干细胞的方案,这些患者通常被选择性地丢弃。我们用间充质干细胞标记物对干细胞进行了表征,并比较了它们与正常骨髓间充质干细胞(MSCs)在培养、倍增和分化成不同谱系中的潜力。我们观察到牙髓中的MSCs生长更快,倍增时间更短,并且在标准定向分化方案下具有相同的分化到各种谱系的效率。本文证实,废弃的高携带牙齿可以作为再生医学的良好来源,也可以作为MSC和牙髓MSC库的潜在来源。
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引用次数: 0
Effect of bFGF on HLA-DR expression of human bone marrow-derived mesenchymal stem cells. bFGF对人骨髓间充质干细胞HLA-DR表达的影响。
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2013-01-01
Pratiksha A Dighe, Pachaiyappan Viswanathan, Ashwin K Mruthunjaya, Raviraja N Seetharam

There has been a steady rise in the therapeutic applications of bone marrow mesenchymal stem cells (BM-MSCs) because of their unique properties of multilineage differentiation and immune modulation as well as the ease in isolation. However, up-regulation of surface HLA-DR levels when maintaining MSCs in culture under the influence of mitotic factors such as Basic fibroblast growth factor (bFGF) is an area of concern when considering them for the purpose of clinical applications. Thus, we investigated the association of bFGF supplemented to the culture media and the surface expression levels of HLA-DR in BM-MSCs in order to optimize the yield, while keeping HLA-DR levels under permissible levels. Human BM-MSCs were culture expanded in the absence of bFGF and in the presence of 1 ng/ml or 2 ng/ml bFGF. The HLA-DR profile of the cultures was analyzed at the end of each passage. On comparing the percent HLA-DR+ cell population at different concentrations as well as absence of bFGF, significant differences were not observed in the HLA-DR expression levels of the MSC cultures which had reached complete confluence. However, variations in HLA-DR expressions levels were seen which could be traced to the age of cells in culture with values drastically reduced to below 4% on maintaining MSCs typically two to three days beyond achieving full confluence. On the basis of the findings from this study, no significant correlation could be established on the effect of bFGF in modulating HLA-DR surface expression of BM-MSCs. Instead, the data are suggestive of the reasoning that the duration for which BM-MSCs are maintained in culture directly influences their phenotypic characteristics in terms of HLA-DR expression levels, with lowest levels achieved on their prolonged maintenance in culture.

骨髓间充质干细胞(BM-MSCs)由于其多系分化和免疫调节的独特特性以及易于分离,在治疗应用方面稳步上升。然而,在有丝分裂因子(如碱性成纤维细胞生长因子(bFGF))的影响下维持培养的MSCs时,表面HLA-DR水平的上调是考虑其临床应用时需要关注的一个领域。因此,我们研究了培养基中添加bFGF与BM-MSCs中HLA-DR表面表达水平的关系,以优化产量,同时将HLA-DR水平保持在允许的水平。在不含bFGF和存在1 ng/ml或2 ng/ml bFGF的情况下培养人BM-MSCs。在每个传代结束时分析培养物的HLA-DR谱。在比较不同浓度下HLA-DR+细胞群百分比以及不含bFGF的情况下,完全融合的MSC培养中HLA-DR表达水平无显著差异。然而,观察到HLA-DR表达水平的变化,这可以追溯到培养细胞的年龄,在维持MSCs通常超过完全融合两到三天的情况下,其值急剧降低至4%以下。基于本研究结果,bFGF对BM-MSCs HLA-DR表面表达的调节作用没有明显的相关性。相反,这些数据提示了这样一种推理,即BM-MSCs在培养中维持的时间直接影响其HLA-DR表达水平的表型特征,在培养中维持的时间越长,HLA-DR表达水平越低。
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引用次数: 0
Quality control measures in cord blood banking in India - critical appraisal and recommendations. 印度脐带血银行的质量控制措施——关键评价和建议。
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2013-01-01 DOI: jsc.2014.8.2.105
Anuradha Vaidya, Smita Singhania

Umbilical cord blood (UCB) is a potential source of primitive hematopoietic stem and progenitor cells (HSPC) available for clinical application to reconstitute the hematopoietic system in patients lacking conventional stem cell donors. In the last decade because the frequency of UCB stem cell transplantation has increased, the quality of UCB available in banks has become an important criterion for the success of any UCB stem cell transplant. Moreover, with the growing numbers of cord blood banks there is not only a need to improvise quality issues but to also develop a more homogenous approach in setting standards and regulations for assessing them. The present article provides an insight on the importance of cord blood banking in India and the impending requirement to provide clarity on certain issues regarding UCB banking. Furthermore, the article discusses about certain practical approaches which could perhaps be referred to as guidelines (and by no means be solely adopted as the only measures) by cord blood banks in India for establishing or maintaining a standard for quality control (QC) measures.

脐带血(UCB)是原始造血干细胞和祖细胞(HSPC)的潜在来源,可用于临床应用,用于重建缺乏常规干细胞供体的患者的造血系统。在过去的十年中,由于UCB干细胞移植的频率增加,银行中可用的UCB质量已成为任何UCB干细胞移植成功的重要标准。此外,随着脐带血库数量的增加,不仅需要临时解决质量问题,而且还需要制定一种更加统一的方法来制定评估脐带血库的标准和法规。本文提供了对印度脐带血银行重要性的见解,以及即将出台的要求,以明确有关脐带血银行的某些问题。此外,本文还讨论了一些可行的方法,这些方法或许可以作为印度脐带血银行建立或维持质量控制(QC)措施标准的指导方针(绝不是唯一的措施)。
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引用次数: 0
Periodontal regeneration by autologous bone marrow mononuclear cells embedded in a novel thermo reversible gelation polymer. 自体骨髓单核细胞包埋在一种新型热可逆凝胶化聚合物中的牙周再生。
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2013-01-01 DOI: jsc.2014.8.2.99
Seshadri Sankaranarayanan, Nadeem Jetty, Jayaprakash S Gadagi, Senthilkumar Preethy, Samuel J K Abraham

Regeneration of bony defects caused by periodontal disease continues to be a challenge for clinicians. Application of stem cells from different tissue sources and scaffolds for regeneration have been reported in animal models but clinical studies with long term follow-ups are limited. Herein we report the three years follow-up of the application of autologous bone marrow mononuclear cells (BMMNCs) embedded in a thermo-reversible gelation polymer (TGP) for periodontal regeneration. A 23-year female patient with advanced periodontitis (class IV gingival recession, probing pocket depth (PPD) of 5 mm and 6 mm in relation to mandibular lateral and central incisors respectively, and clinical attachment level (CAL) of 13 mm) correlated with radiographic evidence of severe horizontal bone loss extending up to the apex of mandibular incisors was selected for the treatment. After debridement, the defect was implanted with BMMNCs impregnated in TGP. Then the clinical parameters and radiographic evaluation were made at periodic intervals of 6, 12, 24 and 36 months. At six months, significant improvement with the clinical parameters (PPD had reduced to 2 mm, clinical attachment level had improved by 6 mm) was observed. At 36 months, the radiograph revealed bone regeneration with improvement in vertical and horizontal bone height. Transplantation of BMMNCs in a novel TGP is safe and results in a relatively significant and stable clinical outcome in horizontal alveolar bony defects.

牙周病引起的骨缺损的再生对临床医生来说仍然是一个挑战。在动物模型中已经报道了不同组织来源的干细胞和支架的再生应用,但长期随访的临床研究有限。在此,我们报告了自体骨髓单核细胞(BMMNCs)包埋在热可逆凝胶化聚合物(TGP)中用于牙周再生的三年随访。我们选择了一名23岁的女性晚期牙周炎患者(IV级牙龈退缩,探测袋深度(PPD)相对于下颌侧切牙和中切牙分别为5 mm和6 mm,临床附着水平(CAL)为13 mm)与x线片证据相关,严重水平骨丢失延伸至下颌门牙尖。清创后,植入TGP浸透的bmmnc。每隔6个月、12个月、24个月、36个月进行临床参数和影像学评价。6个月时,观察到临床参数有显著改善(PPD减少到2mm,临床附着水平提高了6mm)。36个月时,x线片显示骨再生,垂直和水平骨高度改善。bmmnc在新型TGP中移植是安全的,并且在水平牙槽骨缺损中具有相对显著和稳定的临床结果。
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引用次数: 0
Recent advances in the study of limb development: the emergence and function of the apical ectodermal ridge. 肢体发育的最新研究进展:顶端外胚层脊的出现和功能。
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2013-01-01 DOI: jsc.2014.8.2.79
Joaquin Rodriguez-Leon, Ana Raquel Tomas, Austin Johnson, Yasuhiko Kawakami

Vertebrate extremities develop from limb buds, which emerge as paired protrusions in the lateral plate mesoderm. Forelimb buds are located anteriorly and hindlimb buds are positioned posteriorly. The morphogenesis of the limb requires coordinated actions of several organizing centers, among which the apical ectodermal ridge (AER) plays crucial roles in limb development. Recent studies have shown how the life of the AER (induction, maturation, maintenance and regression) is regulated. This regulation includes cell type- and process- specific roles of previously identified molecules, such as fibroblast growth factors (FGFs), Wnts and bone morphogenetic proteins (BMPs). The studies have also revealed several new players, such as Arid3b, R-Spondin 2 and Flrt3. These advances have enhanced the understanding of how the AER is regulated from its emergence to its regression. Progress has also been made in understanding AER function in relation to processes critical for limb development: proximal-distal patterning, anterior-posterior patterning, chondrogenesis and apoptosis. By focusing on two major model systems, chick and mouse embryos, we will review recent advances in combination with relevant previous studies in the development and function of the AER.

脊椎动物的四肢由肢芽发育而来,肢芽在侧板中胚层中以成对的突起形式出现。前肢芽位于前面,后肢芽位于后面。肢体的形态发生需要多个组织中心的协同作用,其中顶端外胚层脊(apical ectodermal ridge, AER)在肢体发育中起着至关重要的作用。最近的研究表明AER的寿命(诱导、成熟、维持和回归)是如何调节的。这种调节包括先前确定的分子的细胞类型和过程特异性作用,如成纤维细胞生长因子(FGFs)、wnt和骨形态发生蛋白(bmp)。这些研究还揭示了几个新的参与者,如Arid3b、R-Spondin 2和Flrt3。这些进展加强了对AER从出现到消退是如何调节的理解。在了解AER功能与肢体发育关键过程的关系方面也取得了进展:近端-远端模式、前后模式、软骨形成和细胞凋亡。本文以鸡胚和小鼠胚两大模型系统为研究对象,结合前人在AER发育和功能方面的相关研究,综述了近年来的研究进展。
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引用次数: 0
Cancer-initiating cells as target for prevention of recurring disease etiology: role of these malignant putative progenitor cells in relapse or metastasis of human cervical carcinoma. 癌起始细胞作为预防疾病复发的靶点:这些假定的恶性祖细胞在人宫颈癌复发或转移中的作用
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2013-01-01 DOI: jsc.2014.8.3/4.233
Bharathi Ramdass, Abhay Chowdhari, Prasad Koka

Evidence suggests that there is a link between high-risk human papillomaviruses (HPVs) and cervical cancer. Studies indicate that persistence of high risk HPVs may determine progression to more severe stages of cervical disease, while the majority of HPV infections are transient and do not seem to be important in cervical carcinogenesis. Earlier studies in different cancers have shown that tumor initiating cells TICs are responsible for tumor formation and progression and interestingly, they are endowed with stem/ progenitor cell properties. In particular, TICs share with stem cells the key feature of self-renewal. The most efficacious therapeutic intervention for cervical cancer is probably vaccination. This review gives an overview on cervical cancer and its potential therapeutic interventions.

有证据表明,高危人类乳头瘤病毒(hpv)与宫颈癌之间存在联系。研究表明,高危HPV的持续存在可能决定宫颈疾病进展到更严重的阶段,而大多数HPV感染是短暂的,似乎在宫颈癌发生中并不重要。早期对不同癌症的研究表明,肿瘤启动细胞tic负责肿瘤的形成和进展,有趣的是,它们被赋予了干细胞/祖细胞特性。特别是,tic与干细胞具有自我更新的关键特征。宫颈癌最有效的治疗干预措施可能是接种疫苗。本文综述了宫颈癌及其潜在的治疗干预措施。
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引用次数: 0
Ayurveda for chemo-radiotherapy induced side effects in cancer patients. 阿育吠陀治疗癌症患者放化疗引起的副作用。
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2013-01-01 DOI: jsc.2014.8.2.115
Kashinath Metri, Hemant Bhargav, Praerna Chowdhury, Prasad S Koka

Chemotherapy drugs and radiotherapy are highly toxic and both damage adjacent healthy cells. Side effects may be acute (occurring within few weeks after therapy), intermediate or late (occurring months or years after the therapy). Some important side effects of chemotherapy are: nausea, vomiting, diarrhea, mucositis, alopecia, constipation etc; whereas radiation therapy though administered locally, can produce systemic side effects such as fatigue, anorexia, nausea, vomiting, alteration in the taste, sleep disturbance, headache, anemia, dry skin, constipation etc. Late complications of these therapies also include pharyngitis, esophagitis, laryngitis, persistent dysphagia, fatigue, hepatotoxicity, infertility and cognitive deficits. These arrays of side effects have a devastating effect on the quality of life of cancer survivors. Due to the inadequacy of most of the radio-protectors and chemo-protectors in controlling the side effects of conventional cancer therapy the complementary and alternative medicines have attracted the view of researchers and medical practitioners more recently. This review aims at providing a comprehensive management protocol of above mentioned chemo-radiotherapy induced side effects based on Ayurveda, which is an ancient system of traditional medicine practiced in Indian peninsula since 5000 BC. When the major side effects of chemo-radiotherapy are looked through an ayurvedic perspective, it appears that they are the manifestations of aggravated pitta dosha, especially under the group of disorders called Raktapitta (haemorrhage) or Raktadushti (vascular inflammation). Based on comprehensive review of ancient vedic literature and modern scientific evidences, ayurveda based interventions are put forth. This manuscript should help clinicians and people suffering from cancer to combat serious chemo-radiotherapy related side effects through simple but effective home-based ayurveda remedies. The remedies described are commonly available and safe. These simple ayurveda based solutions may act as an important adjuvant to chemo-radiotherapy and enhance the quality of life of cancer patients.

化疗药物和放疗都是剧毒的,都会损害邻近的健康细胞。副作用可能是急性的(在治疗后几周内发生),中期或晚期(在治疗后数月或数年发生)。化疗的一些重要副作用有:恶心、呕吐、腹泻、黏膜炎、脱发、便秘等;而放射治疗虽然是局部进行的,但会产生全身副作用,如疲劳、厌食、恶心、呕吐、味觉改变、睡眠障碍、头痛、贫血、皮肤干燥、便秘等。这些治疗的晚期并发症还包括咽炎、食管炎、喉炎、持续性吞咽困难、疲劳、肝毒性、不孕症和认知缺陷。这些副作用对癌症幸存者的生活质量造成了毁灭性的影响。由于大多数放射保护剂和化学保护剂在控制常规癌症治疗的副作用方面的不足,补充和替代药物最近吸引了研究人员和医生的注意。本文旨在提供一种基于阿育吠陀的综合治疗方案,阿育吠陀是公元前5000年以来在印度半岛流传的一种古老的传统医学体系。从阿育吠陀医学的角度来看,化疗的主要副作用似乎是皮塔多沙加重的表现,特别是在称为Raktapitta(出血)或Raktadushti(血管炎症)的疾病组下。在全面回顾古代吠陀文献和现代科学证据的基础上,提出了基于阿育吠陀的干预措施。这篇手稿应该帮助临床医生和癌症患者通过简单而有效的家庭阿育吠陀疗法来对抗与化疗相关的严重副作用。所描述的补救措施通常是可用的和安全的。这些简单的基于阿育吠陀的解决方案可以作为化疗放疗的重要辅助,提高癌症患者的生活质量。
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引用次数: 0
In vitro osteogenic potential of canine adipose derived stem cells. 犬脂肪干细胞体外成骨潜能的研究。
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2012-01-01 DOI: jsc.2013.7.4.201
Mansi K Aparnathi, Jasminkumari A Patel, Ajai K Tripathi, Devshibhai R Barvalia, Chaitanya G Joshi

Stem cells based tissue engineering is a promising approach for the regenerative treatment of various tissue disorders. Adipose tissue is an abundant source of cells which are competent of multipotential differentiation, called adipose-derived stem cells (ADSCs). The present study was contemplated with the objective of assessing the osteogenic differentiation potential of the canine ADSCs in vitro. The canine ADSCs were isolated from adipose tissue around falciform ligament and abdominal subcutaneous fat. Yield of viable ADSCs from both the tissue sources was found to be nearly equivalent. Tissue subjected to trypsinization yielded more viable, but lesser number of cells as compared to collagenase treatment. The stemness of ADSCs was affirmed by reverse transcriptase PCR which exhibited the expression of stem cell specific genes, OCT4 and NANOG.The monolayer of ADSCs was subjected to differentiation into adipogenic and osteogenic lineages. Assessment of the osteogenic potential of ADSCs in vitro opens a new therapeutic horizon for development of in vivo strategies employing autologous stem cell based tissue regeneration in orthopedics.

基于干细胞的组织工程是一种很有前途的再生治疗各种组织疾病的方法。脂肪组织是具有多能分化能力的细胞的丰富来源,称为脂肪来源干细胞(ADSCs)。本研究旨在评估犬ADSCs在体外的成骨分化潜力。从镰状韧带周围脂肪组织和腹部皮下脂肪中分离犬ADSCs。两种组织来源的可活ADSCs的产量几乎相等。与胶原酶处理相比,胰蛋白酶化组织产生了更多的活细胞,但细胞数量较少。逆转录酶PCR证实了ADSCs的干性,显示了干细胞特异性基因OCT4和NANOG的表达。单层ADSCs分化为成脂系和成骨系。体外对ADSCs成骨潜能的评估,为骨科中基于自体干细胞的组织再生的体内策略的发展开辟了新的治疗前景。
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引用次数: 0
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Journal of Stem Cells
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