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Participation of Cultured Mesenchymal Multipotent Stromal Cells inRegeneration of a Large Persisting Defect of Rabbit Radius Bone 培养间充质多能基质细胞参与兔桡骨大面积缺损的再生
Pub Date : 2012-01-27 DOI: 10.2174/1875043501205010001
Mamonov V.E., Shipounova I.N., Sats N.V., B. A.E., Svinareva Da, Proskurina Nv, R. M.M., Chemis A.G., Drize N.I.
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引用次数: 1
Diabetes Mellitus During Pregnancy Interferes with the BiologicalCharacteristics of Wharton's Jelly Mesenchymal Stem Cells 妊娠期糖尿病影响沃顿氏果冻间充质干细胞的生物学特性
Pub Date : 2011-12-30 DOI: 10.2174/1875043501104010103
L. Pierdomenico, P. Lanuti, R. Lachmann, G. Grifone, E. Cianci, L. Gialo, S. Pacella, M. Romano, E. Vitacolonna, S. Miscia, M. Marchisio
Recent research indicates that the origin of obesity and related metabolic disorders is not only caused by genetic and risk factors in adult life (unbalanced diet, insufficient physical activity) but also may be influenced by the perinatal environment. In addition, studies in animal models suggest that the mesenchymal stem cell commitment into pre-adipocytes can already occur during fetal development and perinatal life. Since the number of pre-adipocytes and mature adipocytes is lower in normal subjects than in obese subjects, changes in the prenatal maturational process may play a role in the pathogenesis of obesity and metabolic-associated diseases. Hyperglycemia during pregnancy is related to an increased risk of obesity, early onset of metabolic syndrome and type 2 diabetes in the offspring. For this reason it would be useful to investigate how the perinatal environment may affect fetal mesenchymal stem cells, especially in deregulated gestational diabetes, where the fetal environment is modified in terms of hormone levels and nutrition. Therefore, we have compared Wharton’s jelly mesenchymal stem cells (WJ-MSC) obtained from umbilical cord of both healthy and diabetic mothers, in order to better understand the mechanisms involved in metabolic diseases in offspring of diabetic mothers. Results indicate that WJ-MSC from diabetic mothers display, in contrast to cells from healthy mothers, a higher ability to differentiate towards the adipogenic lineage. This suggests that the diabetic uterine environment may be responsible for a “pre-commitment” that could give rise in the post natal life to an alteration of adipocyte production upon an incorrect diet style, which in turn would produce obesity.
最近的研究表明,肥胖和相关代谢紊乱的起源不仅是由遗传和成年生活中的危险因素(饮食不平衡、身体活动不足)引起的,而且可能受到围产期环境的影响。此外,动物模型研究表明,间充质干细胞向前脂肪细胞的转化在胎儿发育和围产期就已经发生了。由于正常受试者的前脂肪细胞和成熟脂肪细胞数量低于肥胖受试者,产前成熟过程的变化可能在肥胖和代谢相关疾病的发病机制中发挥作用。妊娠期高血糖与后代肥胖、早发代谢综合征和2型糖尿病的风险增加有关。因此,研究围产期环境如何影响胎儿间充质干细胞是有用的,特别是在妊娠糖尿病患者中,胎儿环境在激素水平和营养方面发生了改变。因此,我们比较了从健康母亲和糖尿病母亲的脐带中获得的Wharton’s jelly mesenchymal stem cells (WJ-MSC),以便更好地了解糖尿病母亲后代代谢疾病的机制。结果表明,与来自健康母亲的细胞相比,来自糖尿病母亲的WJ-MSC显示出更高的向脂肪形成谱系分化的能力。这表明,糖尿病子宫环境可能是导致产后生活中由于不正确的饮食方式而导致脂肪细胞生成改变的“前承诺”的原因,而这反过来又会导致肥胖。
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引用次数: 22
Preface - Stem Cells are Finally Starting to Jell 前言-干细胞终于开始凝结
Pub Date : 2011-12-30 DOI: 10.2174/1875043501104010001
C. Borlongan
The advent of stem cells as a tool to decipher the cell’s biology and as a source of transplant therapy to correct aging and diseases has become a core research arena for tissue engineering and regenerative medicine. It is thus fitting that The Open Tissue Engineering and Regenerative Medicine hosts this volume dedicated to a pivotal source of stem cells – the umbilical cord’s Wharton jelly. Much kudos go to lead editor Dr. Giampero La Rocca for organizing this special volume of the journal, comprising of pioneering scientists who have advanced the basic and translational applications of Wharton jelly-derived stem cells (La Rocca, TOTERMJ 2011).
干细胞作为一种破译细胞生物学的工具和一种纠正衰老和疾病的移植疗法的来源,已经成为组织工程和再生医学的核心研究领域。因此,《开放组织工程与再生医学》杂志专门为干细胞的关键来源——脐带的沃顿果冻撰写这一卷书是再合适不过了。主编Giampero La Rocca博士组织了该杂志的这一特别卷,其中包括了推进沃顿果冻衍生干细胞的基础和转化应用的先驱科学家(La Rocca, TOTERMJ 2011)。
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引用次数: 0
Editorial - Connecting the Dots: The Promises of Wharton's Jelly Mesenchymal Stem Cells forTissue Repair and Regeneration 社论-连接点:沃顿果冻间充质干细胞对组织修复和再生的承诺
Pub Date : 2011-12-30 DOI: 10.2174/1875043501104010003
G. Rocca
Mesenchymal stem cells (MSC) constitute a variety of cellular populations which were described first about 35 years ago in the bone marrow (BM) stroma [1]. These years have foreseen an exponential increase of reports pointing out features, stemness, markers, tissue sources and clinical applications of these cells. Cells with MSC features can be isolated from virtually every adult organ in the body, as well from a group of fetus-associated sources (cells derived from the latter tissues are collectively known as perinatal stem cells) [2]. In recent years, the umbilical cord arose as a promising source of mesenchymal stem cells, which can be isolated in relatively high numbers (compared to BM) and should be further cultured and cryopreserved. Wharton’s jelly (WJ) is the main constituent of the umbilical cord. This mature mucous tissue extends from the amniotic epithelium to the perivascular zone of the cord, and contains an abundant extracellular matrix with fibroblast-like or myofibroblast-like cells inside. The high interest for new stem cell sources for the most diverse clinical applications and the amount of data accumulating on WJ-MSC, pushed for the development of this special issue [3].
间充质干细胞(Mesenchymal stem cells, MSC)由多种细胞群组成,大约35年前首次在骨髓基质中被发现。近年来,关于这些细胞的特征、干性、标记物、组织来源和临床应用的报道呈指数级增长。具有间充质干细胞特征的细胞几乎可以从身体的每一个成人器官中分离出来,也可以从一组胎儿相关来源(来自后一组织的细胞统称围产期干细胞)中分离出来。近年来,脐带作为间充质干细胞的一个有希望的来源,可以分离出相对较多的间充质干细胞(与骨髓相比),并应进一步培养和冷冻保存。华顿氏冻(WJ)是脐带的主要成分。这种成熟的粘膜组织从羊膜上皮延伸到脐带的血管周围区,含有丰富的细胞外基质,内部有成纤维细胞样细胞或肌成纤维细胞样细胞。对新干细胞来源最多样化的临床应用的高度兴趣和WJ-MSC的大量数据积累,推动了本期特刊[3]的发展。
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引用次数: 19
Umbilical cord lining membrane and wharton's jelly-derived mesenchymal stem cells: The similarities and differences 脐带内膜与华顿氏胶状间充质干细胞的异同
Pub Date : 2011-12-30 DOI: 10.2174/1875043501104010021
M. Jeschke, G. Gauglitz, T. T. Phan, D. Herndon, K. Kita
The umbilical cord tissue has gained attention in recent years as a source of multipotent cells. Due to its wide- spread availability, the umbilical cord may be an excellent alternative source of cells for regenerative medicine. Anatomically, umbilical cord tissue is constituted of several different parts, and, accordingly, immunostaining of cord tissue sections revealed differential distribution of several markers and extracellular matrix, distinguishing the various layers. Wharton's jelly is the major component filling the inner part of the umbilical cord tissue, and it has been commonly used as a source of obtaining multipotent cells from umbilical cord. We recently reported isolating mesenchymal stem cells from cord lining membrane (sub-amnion). However, because of several anatomically distinct zones found in the umbilical cord, isolated multipotent cells sometimes show heterogeneity. In addition, differences in isolation technique may lead to further variation. In this review, we discuss the similarities and differences between the cells derived from each sub-region, including sub-amnion as recently reported by us. We further explore the specific features and advantages/disadvantages of Wharton's jelly and the other sub-compartments in the umbilical cord tissue as sources of stem cells/multipotent cells.
近年来,脐带组织作为多能细胞的来源引起了人们的关注。由于其广泛的可用性,脐带可能是再生医学细胞的一个极好的替代来源。在解剖学上,脐带组织由几个不同的部分组成,因此,脐带组织切片的免疫染色显示出几种标记物和细胞外基质的差异分布,区分了不同的层。华顿氏冻是填充脐带组织内部的主要成分,它通常被用作从脐带获得多能细胞的来源。我们最近报道了从脐带内膜(羊膜下)分离间充质干细胞。然而,由于在脐带中发现了几个解剖上不同的区域,分离的多能细胞有时表现出异质性。此外,分离技术的差异可能导致进一步的变异。在这篇综述中,我们讨论了来自每个亚区域的细胞之间的异同,包括我们最近报道的羊膜亚区。我们进一步探讨了华顿氏果冻和脐带组织中其他亚区作为干细胞/多能细胞来源的具体特征和优缺点。
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引用次数: 47
Perinatal and Wharton's Jelly-Derived Mesenchymal Stem Cells in Cartilage Regenerative Medicine and Tissue Engineering Strategies 围产期和沃顿的果冻衍生间充质干细胞在软骨再生医学和组织工程策略
Pub Date : 2011-12-30 DOI: 10.2174/1875043501104010072
M. Iacono, R. Anzalone, S. Corrao, M. Giuffré, A. Stefano, P. Giannuzzi, F. Cappello, F. Farina, G. Rocca
Stem cells can be found in embryonic and extraembryonic tissues as well as in adult organs. In particular, research in the last few years has delineated the key features of perinatal stem cells derived from fetus-associated tissues. These cells show multiple differentiation potential, can be easily expanded ex vivo, and raise no ethical concerns as regards their use. Several reports indicate that cells isolated from Wharton's jelly (WJ), the main component of umbilical cord extracellular matrix, are multipotent stem cells that express markers shared by other mesenchymal stem cells (MSC) and give rise to different mature cell types belonging to all three germ layers. Moreover, WJ-MSC display promising hypoimmunogenic and immunomodulatory properties, since they express molecules able to modulate NK cells and expand regulatory T-cell populations. In this review, we focus on the use of perinatal stem cells for regenerative medicine aimed at cartilage repair and regeneration. Cartilage is a specialized connective tissue which has poor regeneration and self-repair capacity in vivo. Traumatic injury or autoimmune processes are among the main causes of cartilage damage and degeneration, for which new hope comes from tissue engineering using stem cells which have undergone chondrocyte-like differentiation. We analyze the in vitro and in vivo data on the use of perinatal stem cells, in particular WJ-MSC, for cartilage regenerative medicine. The high variability of cell sources, the use of different types of scaffolds and matrixes, and the administration of several combinations of growth factors clearly point out the need for further research to optimize this cellular therapy approach and translate the results obtained from bench to clinic.
干细胞可以在胚胎和胚胎外组织以及成人器官中发现。特别是,过去几年的研究已经描述了来自胎儿相关组织的围产期干细胞的关键特征。这些细胞显示出多种分化潜力,可以很容易地在体外扩增,并且在使用时不会引起伦理问题。一些报道表明,从脐带细胞外基质的主要成分——沃顿氏胶质(WJ)中分离出来的细胞是多能干细胞,它们表达其他间充质干细胞(MSC)共有的标记,并产生属于所有三个生殖层的不同成熟细胞类型。此外,WJ-MSC表现出有希望的低免疫原性和免疫调节特性,因为它们表达能够调节NK细胞和扩大调节性t细胞群的分子。在这篇综述中,我们重点介绍围产期干细胞在再生医学中的应用,旨在软骨修复和再生。软骨是一种特殊的结缔组织,在体内具有较差的再生和自我修复能力。创伤性损伤或自身免疫过程是软骨损伤和退变的主要原因之一,利用软骨细胞样分化的干细胞进行组织工程研究给软骨损伤和退变带来了新的希望。我们分析了围产期干细胞,特别是WJ-MSC用于软骨再生医学的体外和体内数据。细胞来源的高度可变性、不同类型支架和基质的使用以及多种生长因子组合的施用清楚地表明,需要进一步研究以优化这种细胞治疗方法,并将从实验室获得的结果转化为临床。
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引用次数: 45
Umbilical Cord Perivascular Cells: A Mesenchymal Cell Source for Treatment of Tendon Injuries 脐带血管周围细胞:治疗肌腱损伤的间充质细胞来源
Pub Date : 2011-12-30 DOI: 10.2174/1875043501104010112
H. Emrani, J. Davies
Objective: To model the healing that umbilical cord perivascular cells effect in equines, we have used human umbilical cord perivascular cells (HUCPVCs) to repair tendon damage in a collagenase tendon injury model in immune- compromised rats. Animals: 48 Nude rats (Crl:NIH-Foxn1 rnu ) of 200-250 g weight were used. Procedure: The Achilles tendon was exposed by blunt dissection and, using a 30G needle, 30 µl of either a mixture of cells (2 x10 5 ) and collagenase, or collagenase alone, was injected close to the musculotendinous junction in the direction of the osteotendinous junction. Results: Harvested tendons showed the presence of HUCPVCs at the site of injury, whose morphology changed from ovoid to elongated over the 30 post-injury experimental time period. Human genes for collagen type 1 and β-actin were expressed at all time points and there was also a significant increase in tendon tensile strength and stiffness by 30 days post-injury in the experimental group. Conclusion: HUCPVCs facilitated regeneration in our model through changes in collagen organization; cell shape and orientation; and increase in mechanical properties over those of the untreated controls. Clinical Relevance: Cell therapy has been shown to be effective in treating tendon injuries, especially in equines. We have recently isolated a mesenchymal cell population from equine umbilical cords that is analogous to a well-characterized HUCPVC population. Our results indicate that HUCPVCs are a putative cell source for treating tendon injuries; and this model could explain the benefits of using analogous cells in equines.
目的:利用人脐带血管周围细胞(HUCPVCs)修复免疫功能受损大鼠胶原酶肌腱损伤模型,模拟马脐带血管周围细胞的愈合作用。动物:选用体重200-250 g的裸大鼠48只(Crl:NIH-Foxn1 rnu)。操作步骤:钝性剥离暴露跟腱,使用30G针,将30µl细胞(2 × 10 5)和胶原酶的混合物,或单独的胶原酶,沿骨腱连接处方向注射到肌腱连接处附近。结果:收获肌腱损伤部位存在hupvcs,在损伤后30个实验时间内,其形态由卵形变为细长形。1型胶原蛋白和β-肌动蛋白的人类基因在各时间点均有表达,实验组损伤后30天肌腱的抗拉强度和刚度均有显著增加。结论:HUCPVCs通过改变胶原组织促进模型再生;细胞的形状和方向;与未经处理的对照组相比,机械性能有所提高。临床意义:细胞疗法已被证明是有效的治疗肌腱损伤,特别是在马。我们最近从马脐带中分离出一个间充质细胞群,类似于一个具有良好特征的HUCPVC群。我们的研究结果表明,HUCPVCs是治疗肌腱损伤的一种假定的细胞来源;这个模型可以解释在马身上使用类似细胞的好处。
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引用次数: 18
Wharton's Jelly Stem Cells as Agents for Cancer Therapy 沃顿的果冻干细胞作为癌症治疗的药剂
Pub Date : 2011-12-30 DOI: 10.2174/1875043501104010039
M. Tamura, A. Kawabata, N. Ohta, L. Uppalapati, K. Becker, D. Troyer
Stem cell based therapy has significant potential to treat various diseases including primary and metastatic cancers. The umbilical cord matrix stem cells (UCMSC) derived from human umbilical cord Wharton's jelly (also termed WJMSC) have been shown to exhibit low immunogenicity, which potentially negates immune consequences after cytotherapy. The homing ability of human and rat UCMSC to inflammatory tissues, including cancer tissues, further confers upon these cells the potential for targeted cancer therapy. Our previous studies demonstrated that un-engineered human and rat UCMSC significantly attenuated the growth of multiple cancer cell lines in vivo and in vitro through multiple mechanisms. We have also demonstrated that these cells can be engineered to express cytotoxic cytokines before being delivered to the tumor and can be preloaded with nanoparticle payloads and attenuate tumors after homing to them. In this review, intrinsic stem cell-dependent regulation of cancer growth, potential mechanisms involved in this unique biological function, delivery of exogenous anti-cancer agents, and the potential for clinical applications will be discussed.
干细胞疗法在治疗包括原发性和转移性癌症在内的各种疾病方面具有巨大的潜力。脐带基质干细胞(UCMSC)来源于人脐带沃顿氏冻(也称为WJMSC),已被证明具有低免疫原性,这可能会在细胞治疗后产生免疫后果。人和大鼠UCMSC对炎症组织(包括癌症组织)的归巢能力,进一步赋予了这些细胞靶向癌症治疗的潜力。我们之前的研究表明,未经工程化的人和大鼠UCMSC通过多种机制在体内和体外显著减弱多种癌细胞系的生长。我们还证明,这些细胞在被运送到肿瘤之前可以被改造成表达细胞毒性细胞因子,并且可以预先装载纳米粒子有效载荷,并在返回肿瘤后减弱肿瘤。在这篇综述中,将讨论干细胞对肿瘤生长的内在依赖调节,这种独特生物学功能的潜在机制,外源性抗癌药物的传递以及临床应用的潜力。
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引用次数: 34
Wharton's Jelly Mesenchymal Stem Cells as Off-The-Shelf CellularTherapeutics: A Closer Look into their Regenerative andImmunomodulatory Properties 沃顿的果冻间充质干细胞作为现成的细胞疗法:对其再生和免疫调节特性的深入研究
Pub Date : 2011-12-30 DOI: 10.2174/1875043501104010028
S. Prasanna, V. S. Jahnavi
Mesenchymal stem/stromal cells (MSCs) are isolated from most post-natal tissues and are broadly reported to have similar immuno-phenotype, mesenchymal lineage-differentiation potential and bio-distribution in peri-vascular niches. Thus, several stromal substitutes of bone marrow mesenchymal stem cells (BMMSCs) are being considered for regenerative therapy. Wharton's jelly mesenchymal stem cells (WJMSCs) seem to be the most promising alternative because of easy donor accessibility, high proliferative capacity and greater sample to sample identity. Recent in vitro and in vivo evidences also support the usage of WJMSCs in tissue repair and regeneration. Key to these observations is secretion of trophic and immune regulatory factors, which aid repair, and resolution of injury. In order to extrapolate these results for clinical usage key questions that need to be addressed are: extrapolation of "allogeneic" transplantation ability of BMMSCs to WJMSCs, survival of allogeneic/xenogeneic WJMSCs in transplantation scenario and actual mechanisms of immune-modulation in an "inflammatory" setting. This review focuses on comparing the in vitro and in vivo studies on immune regulatory properties of WJMSCs and BMMSCs and speculates the usage of WJMSCs for immuno-modulation in a disease scenario. Despite commonalities, different tissue-derived MSCs are reported to have unique gene expression signatures. We would evaluate whether WJMSCs have unique inherent properties, owing to their bio-distribution and primitiveness, as compared to BMMSCs. Further, we debate whether these differences remain conserved on in vitro propagation and impact the immune properties of WJMSCs and speculate the pros and cons of using WJMSCs for allogeneic transplantation. Keyword: Mesenchymal stem cells, immunomodulation, allogenic transplantation.
间充质干细胞(MSCs)是从大多数出生后组织中分离出来的,广泛报道具有相似的免疫表型,间充质谱系分化潜力和血管周围生态位的生物分布。因此,骨髓间充质干细胞(BMMSCs)的几种基质替代品正被考虑用于再生治疗。沃顿的果冻间充质干细胞(WJMSCs)似乎是最有希望的替代方案,因为它容易获得供体,增殖能力高,样本间的一致性更强。最近的体外和体内证据也支持WJMSCs在组织修复和再生中的应用。这些观察的关键是营养和免疫调节因子的分泌,这有助于修复和解决损伤。为了将这些结果外推到临床应用,需要解决的关键问题是:外推BMMSCs对WJMSCs的“异体”移植能力,移植场景中异体/异种WJMSCs的存活以及“炎症”环境下免疫调节的实际机制。本文将比较WJMSCs和BMMSCs在体内和体外对免疫调节特性的研究,并推测WJMSCs在疾病情况下的免疫调节作用。尽管存在共性,但据报道,不同组织来源的间充质干细胞具有独特的基因表达特征。由于WJMSCs的生物分布和原始性,我们将评估WJMSCs是否具有与BMMSCs相比的独特固有特性。此外,我们讨论这些差异是否在体外繁殖中保持保守并影响WJMSCs的免疫特性,并推测使用WJMSCs进行同种异体移植的利弊。关键词:间充质干细胞,免疫调节,同种异体移植
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引用次数: 54
Phenotype and Differentiation Potential of Stromal Populations Obtained from Various Zones of Human Umbilical Cord: An Overview 人类脐带不同区域间质群体的表型和分化潜力综述
Pub Date : 2011-12-30 DOI: 10.2174/1875043501104010006
M. Conconi, R. Liddo, M. Tommasini, C. Calore, P. Parnigotto
Fibroblast-like cells with properties similar to mesenchymal stromal cells (MSCs) are present in human umbilical cord (hUC). In accordance with the international minimal criteria for defining multipotent mesenchymal stromal cells, hUC cells are designed MSCs being plastic adherent, positive to specific non hematopoietic lineage biomarkers, able to be both in vitro long term cultured and differentiated into osteoblasts, chondroblasts and adipocytes. In this review, a panoramic view of phenotypic characteristics of hUC cells derived from various UC parts are described. The high heterogeneity of extraction, culture and analysis procedures hinder the ability to precisely identify UC stromal cells. As a result, different phenotypic profiles are detectable not only among the cells obtained from the various parts of cord, but also inside the same UC regions, suggesting that UC-MSCs may represent an unique cell family whose components present various degree of stemness. However, in vitro and in vivo evidence indicates Wharton's jelly as the best source of MSCs, because its cells present a wide range of potential therapeutic applications.
具有类似间充质间质细胞(MSCs)特性的成纤维细胞样细胞存在于人脐带(hUC)中。根据定义多能间充质基质细胞的国际最低标准,hUC细胞被设计为具有可塑性粘附性的MSCs,对特定的非造血谱系生物标志物呈阳性,能够在体外长期培养并分化为成骨细胞、成软骨细胞和脂肪细胞。在这篇综述中,描述了来自UC不同部位的UC细胞的表型特征的全景视图。提取、培养和分析过程的高度异质性阻碍了精确鉴定UC间质细胞的能力。因此,不仅在脐带不同部位获得的细胞中可以检测到不同的表型谱,而且在相同的UC区域内也可以检测到不同的表型谱,这表明UC- mscs可能代表了一个独特的细胞家族,其成分具有不同程度的干性。然而,体外和体内的证据表明,沃顿水母是间充质干细胞的最佳来源,因为它的细胞具有广泛的潜在治疗应用。
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引用次数: 74
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The open tissue engineering and regenerative medicine journal
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