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Comparison of ayoub shklar stain and routine haematoylin and eosin stain for the keratin identification in kcot–a pilot study ayoub shklar染色与常规血红素和伊红染色在kcot中鉴定角蛋白的比较——一项初步研究
Pub Date : 2018-06-27 DOI: 10.15406/JSRT.2018.04.00116
Aiman Zafar, P. Ramani, N. Anuja, H. Sherlin, Gheena, R Abhilasha, Giffrina Jayaraj, K. Don
Keratins are one of the major and key structural proteins, found at their highest concentration and diversity in the keratinocytes of cutaneous as well as oral epithelium and accounts for almost 80% of the total protein content in differentiated cells of stratified epithelia. In the 1900s, keratins were believed to be the proteins, which could be extracted from the various epidermal modifications of animals such as wool, horns, claws, etc.1,2 Subsequently, with advancement in research and advent of 21st century technologies, keratin(cytokeratins) are now considered as intermediate filament proteins with specific physicochemical properties, found in any vertebrate epithelia.2 They are part of the multi-gene family of proteins, occurring in basic and acidic protein pairs with varied expression pattern in different types of epithelia, as well as different layers of a single stratified epithelium. The main function of cytokeratins along with microtubules and microfilaments is to provide with structural integrity and mechanical resiliency to all the eukaryotic cells. The oral epithelium can be categorized into keratinized stratified epithelia (ortho and parakeratinized) and non-keratinized epithelia based on the presence or absence of keratinization. Keratinization or cornification involves the process of cytodifferentiation of the keratinocytes, starting from their post formative state, i.e., stratum basale to the final differentiated state of toughened cornified cells filled with keratin filaments found in the surface layer, i.e., stratum corneum.
角蛋白是主要和关键的结构蛋白之一,在皮肤和口腔上皮的角化细胞中含量最高,多样性也最高,几乎占分层上皮分化细胞总蛋白含量的80%。在20世纪初,角蛋白被认为是一种可以从动物的各种表皮修饰物中提取的蛋白质,如羊毛、角、爪等。随后,随着研究的进步和21世纪技术的出现,角蛋白(细胞角蛋白)现在被认为是一种具有特定物理化学性质的中间丝蛋白,存在于任何脊椎动物的上皮中它们是多基因蛋白家族的一部分,出现在碱性和酸性蛋白对中,在不同类型的上皮以及单个分层上皮的不同层中表达模式不同。细胞角蛋白与微管和微丝的主要功能是为真核细胞提供结构完整性和机械弹性。根据有无角化,口腔上皮可分为角化层状上皮(正角化和角化过度)和非角化上皮。角化或角化涉及到角化细胞的细胞分化过程,从它们形成后的状态(即基底层)开始,到最终的分化状态,即表面层(即角质层)中充满角蛋白丝的变韧的角化细胞。
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引用次数: 0
Lipoproteins as drug delivery vehicles for cancer and tumor therapeutics 脂蛋白作为癌症和肿瘤治疗的药物传递载体
Pub Date : 2018-06-25 DOI: 10.15406/JSRT.2018.04.00115
R. Upadhyay
Lipoproteins are biological lipid carriers play important role in transport of fats within the body.1 These are natural nanoparticles which serve as drug-delivery vehicles due to their small size, long residence time in the circulation.2 Low-density lipoprotein (LDL) carries cholesterol in plasma3 and play important role in its metabolism in normal cells as well as in cancer cells.4 Lipoproteins carry highdrug payload and are used as delivery vehicles for transportation of chemotherapeutic agents. These bear unique targeting capabilities because of their easy transportation to cancer and tumor sites. LDL loaded with r11-DOX is used to treat cancer cells. LDL follows receptor pathway is used to deliver radionucleotides for the treatment of neoplasms and tumors.5 Both liposomes and oil emulsions are also used to carry water-insoluble photosensitizers for treatment of tumors.6 Besides, low-density lipoproteins (LDLs) monoclonal antibodies are also most promising delivery vehicles for anticancer drugs. For delivery of therapeutic agents liposomes bind to some antibody and loaded drug are internalized by into macrophages via the receptor-mediated pathway for modified LDL.7 More specifically, loaded drug is assimilated through receptor-mediated pathway in cancer cells and its rate is much higher than that of normal cells. For transport of drugs to new targets, lipoproteins are bound to ligands. Lipoproteins structure is modified to tag nucleic acids, photosensitizers for therapeutics. These also act as biophysical devices like contrast agents and can be loaded with drugs, LPs and phospholipids. These natural drug nanocarriers escape any interaction with immune cells and reticuloendothelial systems.8 Hence, drugs loaded on LDLs safely transported to tumor cells without loss of their activity.9 After receptor-mediated uptake of drug-lipoprotein complex escape enzyme attack.2 Lipoproteins are safe, biocompatible, biodegradable, nonimmunogenic and successfully carry diverse therapeutic molecules to the site of invasion. Lipoproteins: transport vehicles of lipids
脂蛋白是生物脂质载体,在体内脂肪的运输中起着重要作用这些是天然的纳米颗粒,由于它们体积小,在循环中停留时间长,可以作为药物输送载体低密度脂蛋白(LDL)在血浆中携带胆固醇,在正常细胞和癌细胞的代谢中起重要作用脂蛋白携带高药物载荷,是化疗药物运输的运载工具。它们具有独特的靶向能力,因为它们易于运输到癌症和肿瘤部位。LDL装载r11-DOX用于治疗癌细胞。低密度脂蛋白跟随受体途径被用于传递放射性核苷酸,用于肿瘤和肿瘤的治疗脂质体和油乳剂也用于携带水不溶性光敏剂治疗肿瘤此外,低密度脂蛋白(ldl)单克隆抗体也是最有前途的抗癌药物递送载体。为了递送治疗剂,脂质体结合某些抗体和载药通过受体介导的途径内化到巨噬细胞中,以修饰ldl。更具体地说,载药通过受体介导的途径在癌细胞中被吸收,其吸收率远高于正常细胞。为了将药物运输到新的靶点,脂蛋白与配体结合。修饰脂蛋白结构以标记核酸,光敏剂用于治疗。它们也像造影剂一样作为生物物理设备,可以装载药物、脂多糖和磷脂。这些天然药物纳米载体可避免与免疫细胞和网状内皮系统相互作用因此,装载在ldl上的药物安全运输到肿瘤细胞而不丧失其活性受体介导的药物-脂蛋白复合物摄取后逃逸酶攻击脂蛋白是安全的、生物相容性的、可生物降解的、非免疫原性的,并能成功地将各种治疗分子运送到侵袭部位。脂蛋白:脂质的运输载体
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引用次数: 6
Bioprinting and stem cells: the new frontier of tissue engineering and regenerative medicine 生物打印和干细胞:组织工程和再生医学的新前沿
Pub Date : 2018-05-18 DOI: 10.15406/JSRT.2018.04.00114
Thaís Vieira de Souza, A. R. Santos, S. M. Malmonge
Stem cells (SC) have great capacity for proliferation and differentiation. Some of their characteristics are self-renewal, the ability to differentiate into more than one cell line and the ability to originate functional cells in tissues derived from the same lineage.1 These important properties led several research groups to seek the use of stem cells as the main agent in the treatment of diseases, which has come to be called cell therapy. Promising results from various study groups have stimulated different centers around the world to initiate clinical trials that have investigated the feasibility of SC transplantation for the treatment of various diseases. Many interesting and other disappointing results have been reported.2
干细胞具有很强的增殖和分化能力。它们的一些特征是自我更新、分化成多个细胞系的能力,以及在来自同一细胞系的组织中产生功能性细胞的能力这些重要的特性促使几个研究小组寻求使用干细胞作为疾病治疗的主要药物,这被称为细胞疗法。来自不同研究小组的有希望的结果刺激了世界各地不同的中心开展临床试验,研究SC移植治疗各种疾病的可行性。已经报道了许多有趣的和其他令人失望的结果
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引用次数: 3
Diabetes: stem cells offering healthy promises 糖尿病:干细胞带来健康的希望
Pub Date : 2018-05-09 DOI: 10.15406/JSRT.2018.04.00113
A. Saraswat, An, Srivastava
Diabetes is a chronic lifelong disease and according to Diabetes Association of America, in 2015 itself approximately 30.3million Americans (9.4% of the population) have the disease. Unfortunately, almost one fourth (or approximately 7.2million) are unaware that they have it. An additional 84.1million people have pre-diabetes. With increasing prosperity, its prevalence has increased in almost all populations of the world and ranges from 5-15%. As it affects so big portion of the world population a long-lasting cure is urgently warranted. People with diabetes need to manage their disease in order to avoid related complications and maintain healthy social and economic interactions.
糖尿病是一种慢性终身疾病,根据美国糖尿病协会的数据,2015年约有3030万美国人(占人口的9.4%)患有糖尿病。不幸的是,几乎有四分之一(或大约720万)的人没有意识到自己患有糖尿病。另外还有8410万人处于糖尿病前期。随着日益繁荣,它在世界上几乎所有人口中的流行率都有所增加,范围从5-15%不等。由于它影响到世界人口的很大一部分,因此迫切需要一种持久的治疗方法。糖尿病患者需要控制自己的疾病,以避免相关并发症并保持健康的社会和经济互动。
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引用次数: 0
Mesenchymal stem cells for pre-vascularization of engineered tissues 用于工程组织预血管化的间充质干细胞
Pub Date : 2018-04-19 DOI: 10.15406/JSRT.2018.04.00112
Dhavan Sharma, Juan Chica, F. Zhao
Recent advances in the field of stem cell biology and tissue engineering have revolutionized therapeutic approaches to treat various diseases, especially chronic wounds, bone diseases, cardiovascular complications, and neurodegenerative diseases. Different stem cell types have been investigated for designing appropriate therapeutic treatments. Among them, approaches involving embryonic and induced pluripotent stem cells (iPSCs) are ethically and socially controversial. In addition, these stem cell types, due to their high pluripotency, contain risks of teratoma formation.1,2 In the past decade, mesenchymal stem cells (MSCs) have attracted considerable attention due to their straightforward and less invasive isolation procedure as well as their multi-differentiation potential. MSCs can differentiate into various cell types including osteoblasts, chondrocytes, adipocytes, smooth muscle like cells, endothelial like cells and cardiomyocyte like cells. Moreover, being immunoprivileged, allogenic MSCs encounter minimal risk of immune rejection. They also secrete various trophic factors, which can promote cell survival and tissue regeneration.3,4 These promising capabilities have made MSCs potential candidate for construction of various tissue-engineered products. Nevertheless, engineered tissues with a thickness larger than 150μm require a functional micro vascular network to supply gases, nutrients, metabolic byproducts, and integrate with host vasculature after implantation.5 In the physiological capillary structure, endothelial cells (ECs) surround the vessel lumen. These ECs are themselves wrapped by pericytes, which stabilize the capillary structure.6 Numerous studies have confirmed that MSCs can function as pericytes.7,8 Consequently, in order to develop a capillary network in tissue scaffolds various research groups over past several years have investigated the outcome of MSC-EC co-cultures.9‒12 Compared with other pericyte candidates, MSCs are expected to play dual roles: stabilizing engineered micro vessels and performing their stem cell functions after implantation. In this mini review, we discuss important considerations for successful MSC-EC co-cultures to achieve a robust vascular network. These considerations include an appropriate cell source, cell-seeding order, optimum oxygen (O2) levels, appropriate extracellular matrix (ECM) and tissue scaffold features (Figure 1). Figure 1 Considerations for MSC-EC co-culture for development of prevascularized engineered tissues. (A) Various sources from which MSCs can be isolated, (B) MSCs can be cultured on preformed vascular networks formed by ECs. In contrast, ECs cultured on MSC sheet forms better vascular networks, (C) MSCs maintain stemness and increase angiogenic growth factor secretion in a hypoxic environment. Whereas, ECs prefer normoxic environment for cell survival, proliferation and development of vascular networks, (D) Various natural and synthetic materials support MSC-EC co-culture.
干细胞生物学和组织工程领域的最新进展已经彻底改变了治疗各种疾病的方法,特别是慢性伤口、骨骼疾病、心血管并发症和神经退行性疾病。为了设计合适的治疗方法,研究了不同类型的干细胞。其中,涉及胚胎和诱导多能干细胞(iPSCs)的方法在伦理和社会上都存在争议。此外,这些干细胞类型,由于其高度多能性,包含畸胎瘤形成的风险。1,2在过去的十年中,间充质干细胞(MSCs)因其简单、微创的分离过程以及其多向分化的潜力而引起了广泛的关注。MSCs可分化为成骨细胞、软骨细胞、脂肪细胞、平滑肌样细胞、内皮样细胞和心肌样细胞等多种细胞类型。此外,由于具有免疫特权,同种异体间充质干细胞遭遇免疫排斥的风险最小。它们还分泌各种营养因子,促进细胞存活和组织再生。这些有希望的能力使MSCs成为构建各种组织工程产品的潜在候选者。然而,厚度大于150μm的工程组织需要一个功能性的微血管网络来供应气体、营养物质、代谢副产物,并在植入后与宿主血管系统整合在生理性毛细血管结构中,内皮细胞(ECs)包围着血管腔。这些内皮细胞本身被周细胞包裹,周细胞稳定毛细血管结构大量研究证实MSCs具有周细胞的功能。因此,为了在组织支架中建立毛细血管网络,在过去的几年中,各种研究小组研究了MSC-EC共培养的结果。与其他候选周细胞相比,MSCs有望发挥双重作用:稳定工程微血管并在植入后发挥其干细胞功能。在这篇综述中,我们讨论了成功的MSC-EC共培养以实现强健血管网络的重要考虑因素。这些考虑因素包括合适的细胞来源、细胞播种顺序、最佳氧(O2)水平、合适的细胞外基质(ECM)和组织支架特征(图1)。图1 MSC-EC共培养用于培养预血管化工程组织的考虑因素。(A)可以分离MSCs的各种来源,(B) MSCs可以在由ECs形成的预先形成的血管网络上培养。相比之下,在MSC薄片上培养的内皮细胞形成了更好的血管网络,(C) MSCs在缺氧环境下保持干性并增加血管生成生长因子的分泌。(D)多种天然和合成材料支持MSC-EC共培养。脱细胞的ECM促进强健血管网络的发展。
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引用次数: 7
Retinyl acetate mediates autocrine proliferation and wound healing of keratinocytes through a c-neu (erbB-2)-like receptor 醋酸视黄酯通过c-neu (erbB-2)样受体介导角质形成细胞的自分泌增殖和伤口愈合
Pub Date : 2018-04-10 DOI: 10.15406/JSRT.2018.04.00111
J. Wille, Jong Y. Park
Pleiotropic effects of retinoids on cell growth signal transduction and receptor-mediated gene regulation are well documented.1,2 The use of chemically-defined serum free medium (SFM) has identified two protein growth factors, EGF and insulin, that are required for normal human keratinocytes (NHK) proliferation in low calcium (<1mM) SFM medium.3,4 The role of retinoids in regulating proliferation of normal human keratinocytes is less well-understood. For example, all-trans retinoic acid (t-RA) stimulates proliferation in essential fatty acid-supplemented keratinocytes.5 Retinoic acid (t-RA, 10-7M) treatment inhibited proliferation of HaCaT cells adapted to serumfree DME/Hams F12 medium, while retinol (ROL, 10-7M) did not, but overall growth in this SFM was much curtailed.6 By contrast, a panel of retinoids including t-RA, ROL, 13-cis RA, all inhibited the clonal growth of NHK in SFM supplemented with EGF and insulin in rapidly proliferating NHK.7 The strength of inhibition was linearly correlated with their ability to suppress both ornithine decarboxylase enzyme induction by tumor promoter and papilloma formation in the mouse skin model of tumorigenesis. 7 By contrast, t-RA stimulates growth-arrested adult keratinocytes in protein growth factor-deficient SFM.8 These conflicting effects appear to involve differing growth media conditions. Verani et al.9 also reported that induced alterations in membrane intracellular calcium ion fluctuations appear to underlie retinoid growth stimulation.9 Retinoid stimulation of growth-arrested NHK was also found to involve autocrine production of a heparinbonding EGF (hb-EGF), and activation of erbB receptors10 present on suprabasal cells. Moreover, autocrine stimulation via these signaling pathways appears to underlie retinoid-induced epidermal hyperplasia.10 Recently, t-RA was reported to inhibit the expression of the erbB (c-neu) receptor and other proto-oncogenes in several different epidermoid carcinoma cell lines.11 In addition, t-RA reverses the super-induction by alcohol of aryl hydrocarbon hydrylase induced by benzo(α) pyrene in SFM culture of NHK.12 Retinoids also have profound effects on epidermal keratinocyte differentiation in many different tumor cells lines.13 Retinyl acetate (RetAc) is a naturally occurring fatty acid ester of retinol, and is less toxic than t-RA. It is stored in human liver and is involved to metabolic conversion to vitamin A (retinol). Here, we explore the effect of RetAc on the clonal growth of NHK and HaCaT cells treated with different combinations of EGF and insulin. We established that serum can be dispensed with by culturing HaCaT keratinocytes in SFM supplemented with EGF and insulin. This allowed us to conduct detailed clonal assay to determine their minimal growth factor requirements. Clonal growth assay studies also examined the effect of RetAc. Unlike t-RA,7 we report that RetAc stimulates HaCaT clonal growth at physiological levels. We further explored the underlying
类维生素a对细胞生长、信号转导和受体介导的基因调控的多效性作用已被充分证实。1,2使用化学定义的无血清培养基(SFM)已经确定了两种蛋白质生长因子,EGF和胰岛素,它们是正常人角质形成细胞(NHK)在低钙(<1mM) SFM培养基中增殖所必需的。3,4类维生素a在调节正常人角质形成细胞增殖中的作用尚不清楚。例如,全反式维甲酸(t-RA)刺激必需脂肪酸补充的角化细胞增殖视黄酸(t-RA, 10-7M)抑制了适应无血清DME/Hams F12培养基的HaCaT细胞的增殖,而视黄醇(ROL, 10-7M)没有,但这种SFM的总体生长受到很大抑制相比之下,一组类维生素a包括t-RA、ROL、13-顺式RA,在快速增殖的NHK中,在补充了EGF和胰岛素的SFM中,都抑制了NHK的克隆生长。7抑制强度与它们抑制肿瘤启动子诱导鸟氨酸脱羧酶的能力和抑制肿瘤发生小鼠皮肤模型中乳头状瘤的形成能力呈线性相关。相比之下,t-RA刺激蛋白生长因子缺乏的sfm中生长受阻的成人角化细胞。8这些相互冲突的影响似乎涉及不同的生长介质条件。Verani等人也报道了细胞膜内钙离子波动的诱导改变似乎是类视黄醇生长刺激的基础对生长受阻的NHK的类视黄醇刺激也被发现涉及肝素结合的EGF (hb-EGF)的自分泌,以及存在于基底上细胞的erbB受体的激活。此外,通过这些信号通路的自分泌刺激似乎是类视黄酮诱导的表皮增生的基础最近,有报道称t-RA在几种不同的表皮样癌细胞系中抑制erbB (c-neu)受体和其他原癌基因的表达此外,t-RA逆转了乙醇对苯并(α)芘诱导的nhk SFM培养中芳烃水解酶的超诱导作用。类维生素a还对许多不同肿瘤细胞系表皮角质形成细胞的分化有深远的影响视黄醇醋酸酯(RetAc)是一种天然存在的视黄醇脂肪酸酯,毒性比t-RA小。它储存在人体肝脏中,参与代谢转化为维生素A(视黄醇)。在这里,我们探讨了RetAc对不同EGF和胰岛素组合处理的NHK和HaCaT细胞克隆生长的影响。我们发现,HaCaT角质形成细胞可以在添加EGF和胰岛素的SFM中培养,无需血清。这使我们能够进行详细的克隆测定,以确定其最低生长因子需求。克隆生长试验研究也检验了RetAc的效果。与t-RA不同,我们报道RetAc在生理水平上刺激HaCaT克隆生长。我们进一步探讨了潜在的生化事件,揭示了自分泌信号通路和c-neu (erbB-2)细胞质受体的可能参与,以及治疗诱导的病灶膜区易位。最后,我们检验了效果
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引用次数: 0
Determination of her2 overexpression in patients with osteosarcoma 骨肉瘤患者her2过表达的测定
Pub Date : 2018-04-05 DOI: 10.15406/JSRT.2018.04.00110
Zaki Antonio Taissoun-Aslan, L. H. Montalvo, J. D. Chávez, D. C. León, A. Gómez-Pedraza, M. L. Serrano-Arévalo, Andrea Moreno-Tobon, Mateo Mejía Saldarriaga
Abbreviations: CEP 17, chromosome enumeration probe 17; DAB, diaminobenzidine; EGFR, epidermal growth factor receptor; FISH, fluorescent in situ hybridization; H&E, hematoxylin and eosin; her2/neu, human epidermal growth factor receptor 2; HR, hormone receptors; IHC, immunohistochemistry; OS, osteosarcoma; PBS, phosphate-buffered saline; PCR, polymerase chain reaction; PD-l1, tumor programed cell death ligand 1
缩写词:CEP 17,染色体枚举探针17;轻拍,diaminobenzidine;表皮生长因子受体;FISH,荧光原位杂交;H&E、苏木精和伊红;Her2 /neu,人表皮生长因子受体2;HR,激素受体;包含IHC,免疫组织化学;操作系统,骨肉瘤;PBS,磷酸盐缓冲盐水;聚合酶链式反应;PD-l1,肿瘤程序性细胞死亡配体1
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引用次数: 0
Retrospective analysis of role of autologous bone marrow derived mononuclear stem cells in the management of degenerative arthritis of knee 自体骨髓来源的单个核干细胞在膝关节退行性关节炎治疗中的作用回顾性分析
Pub Date : 2018-03-14 DOI: 10.15406/JSRT.2018.04.00109
B. Rajput, R. Kulkarni, A. Bopardikar, Pradeep Somalapur, Raghwendra Kumar
Osteoarthritis (OA) Knee is the most common disease of the joints and a leading cause of chronic disability, especially in the aged population.1 The pathogenesis of OA knee has been linked to biomechanical and biochemical changes in joint cartilage, e.g. inability to withstand normal mechanical stresses, limited nutrients and oxygen supply, inadequate synthesis of extracellular matrix components, increased synthesis of proteinases and overall apoptosis of chondrocytes.2–5 Synovial inflammation is a response of synovial macrophages to cartilage debris and catabolic mediators entering the synovial cavity which limits the cartilage repair.6
骨关节炎(OA)膝关节是最常见的关节疾病,也是慢性残疾的主要原因,尤其是在老年人中OA膝的发病机制与关节软骨的生物力学和生化变化有关,如不能承受正常的机械应力、营养和氧气供应有限、细胞外基质成分合成不足、蛋白酶合成增加和软骨细胞整体凋亡。滑膜炎症是滑膜巨噬细胞对进入滑膜腔的软骨碎片和分解代谢介质的反应,这限制了软骨的修复
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引用次数: 4
Embryonic and mesenchymal stem cells: An examination of the rapidly narrowing gap between their proven abilities 胚胎干细胞和间充质干细胞:对它们已证实的能力之间迅速缩小差距的检查
Pub Date : 2018-03-12 DOI: 10.15406/JSRT.2018.04.00108
A. Hill, J. M. Garcia
Stem cell therapy and biology have displayed increasingly concrete potential resolutions to a diversity of obstacles in the treatment of chronic and degenerative diseases over the past decade. Encouraging results continue to be generated, further increasing the amount of interest in the field and the number of studies performed, giving hope to patients with, until now, incurable chronic and degenerative diseases with few new ideas on the horizon.
在过去的十年中,干细胞治疗和生物学已经显示出越来越具体的潜在解决方案,以治疗慢性和退行性疾病的各种障碍。令人鼓舞的结果继续产生,进一步增加了对该领域的兴趣和进行的研究的数量,给迄今为止无法治愈的慢性和退行性疾病的患者带来了希望,几乎没有新的想法。
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引用次数: 0
Efficacy of umbilical cord tissue derived mesenchymal stem cells in the management of advanced rheumatoid polyarthritis 脐带组织源性间充质干细胞治疗晚期类风湿多发性关节炎的疗效
Pub Date : 2018-02-27 DOI: 10.15406/JSRT.2018.04.00107
Bs Rajput, Rani James, S. Kudari
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引用次数: 1
期刊
Journal of stem cell research & therapeutics
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