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1.
Regeneration effects with cellular factors are considered essential in regenerative treatments. Cellular factors derived from multiple cells can be applied in such therapies. Various clinical trial phases are based on studies of mesenchymal stem and progenitor cells (MSPCs). Mesenchymal stem cells (MSCs) are pluripotent stem cells which have multi-directional differentiation potential. MSPCs may exhibit full stem cell functions and can be obtained from different tissues, such as adipose tissue, umbilical cord and bone marrow etc. MSPCs reside in the perivascular niche that is proximal to blood vessels, which allow MSPCs capable of exerting their potential of homing and migration across the endothelium barrier toward lesion sites for tissue repairing or regeneration. MSPCs can be stimulated to release various factors, including surface molecules, growth factors and inhibitory factors. MSPCs’ homing potential depends on the expressing of certain surface molecules. The growth and inhibitory factors contribute to tissue regeneration and immunomodulation effects. This review provides details of how cellular factors derived from MSPCs can be used for homing and repair mechanisms, and ultimately be applied to clinical settings.  相似文献   

2.
Bone is a highly vascularized tissue reliant on the close spatial and temporal association between bloodvessels and bone cells. Therefore, cells that participate in vasculogenesis and osteogenesis play a pivotal role in bone formation during prenatal and postnatal periods. Nevertheless, spontaneous healing of bone fracture is occasionally impaired due to insufficient blood and cellular supply to the site of injury. In these cases, bone regeneration process is interrupted, which might result in delayed union or even nonunion of the fracture. Nonunion fracture is difficult to treat and have a high financial impact. In the last decade, numerous technological advancements in bone tissue engineering and cell-therapy opened new horizon in the field of bone regeneration. This review starts with presentation of the biological processes involved in bone development, bone remodeling, fracture healing process and the microenvironment at bone healing sites. Then, we discuss the rationale for using adult stem cells and listed the characteristics of the available cells for bone regeneration. The mechanism of action and epigenetic regulations for osteogenic differentiation are also described. Finally, we review the literature for translational and clinical trials that investigated the use of adult stem cells(mesenchymal stem cells, endothelial progenitor cells and CD34+ blood progenitors) for bone regeneration.  相似文献   

3.
The discovery that adipose tissue represents an interesting source of multipotent stem cells has led to many studies exploring the clinical potential of these cells in cell-based therapies. Recent advances in understanding the secretory capacity of adipose tissue and the role of adipokines in the development of obesity and associated disorders have added a new dimension to the study of adipose tissue biology in normal and diseased states. Subcutaneous adipose tissue forms the interface between the clinical application of regenerative medicine and the establishment of the pathological condition of obesity. These two facets of adipose tissue should be understood as potentially related phenomena. Because of the functional characteristics of adipose stem cells, these cells represent a fundamental tool for understanding how these two facets are interconnected and could be important for therapeutic applications. In fact, adipose tissue stem cells have multiple functions in obesity related to adipogenic, angiogenic and secretory capacities. In addition, we have also previously described a predominance of larger blood vessels and an adipogenic memory in the subcutaneous adipose tissue after massive weight loss subsequent to bariatric surgery(ex-obese patients). Understanding the reversibility of the behavior of adipose stem cells in obeses and in weight loss is relevant to both physiological studies and the potential use of these cells in regenerative medicine.  相似文献   

4.
In facing the mounting clinical challenge and suboptimal techniques of craniofacial bone defects resulting from various conditions, such as congenital malformations, osteomyelitis, trauma and tumor resection, the ongoing research of regenerative medicine using stem cells and concurrent advancement in biotechnology have shifted the focus from surgical reconstruction to a novel stem cell-based tissue engineering strategy for customized and functional craniofacial bone regeneration. Given the unique ontogenetical and cell biological properties of perinatal stem cells, emerging evidence has suggested these extraembryonic tissue-derived stem cells to be a promising cell source for extensive use in regenerative medicine and tissue engineering. In this review, we summarize the current achievements and obstacles in stem cell-based craniofacial bone regeneration and subsequently we address the characteristics of various types of perinatal stem cells and their novel application in tissue engineering of craniofacial bone. We propose the promising feasibility and scope of perinatal stem cell-based craniofacial bone tissue engineering for future clinical application.  相似文献   

5.
Local signals in stem cell-based bone marrow regeneration   总被引:9,自引:0,他引:9  
Han W  Yu Y  Liu XY 《Cell research》2006,16(2):189-195
The cellular basis of bone marrow (BM) tissue development and regeneration is mediated through hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). Local interplays between hematopoietic cells and BM stromal cells (BMSCs) determine the reconstitution of hematopoiesis after myelosuppression. Here we review the BM local signals in control of BM regeneration after insults. Hematopoietic growth factors (HGFs) and cytokines produced by BMSCs are primary factors in regulation ofBM hematopoiesis. Morphogens which are critical to early embryo development in multiple species have been added to the family of HSCs regulators, including families of Wnt proteins, Notch ligands, BMPs, and Hedgehogs. Global gene expression analysis of HSCs and BMSCs has begun to reveal signature groups of genes for both cell types. More importantly, analysis of global gene expression coupled with biochemical and biological studies of local signals during BM regeneration have strongly suggested that HGFs and cytokines may not be the primary local regulators for BM recovery, rather chemokines (SDF- 1, FGF-4) and angiogenic growth factors (VEGF-A, Ang- 1) play instructive roles in BM reconstitution after myelosuppression. A new direction of management of BM toxicity is emerging from the identification of BM regenerative regulators.  相似文献   

6.
Nayernia K 《Cell research》2007,17(11):895-897
The continuation of the spermatogenic process through-out life relies on a proper regulation of self-renewal and differentiation ofgermline testis stem cells, the spermatogonial stem cells. These are single cells situated on the basal membrane of the seminiferous epithelium. Only 0.03% of all germ cells are spermatogonial stem cells (SSCs) [1-3]. To maintain spermatogenesis, the processes of self-renewal and differentiation of S SCs must be precisely regulated by intrinsic gene expression in the stem cells and extrinsic signals, including soluble factors or adhesion molecules from the surrounding microenvironment, the stem cell niche.[第一段]  相似文献   

7.
Within the epidermis and dermis of the skin, cells secrete and are surrounded by the extracellular matrix(ECM), which provides structural and biochemical support. The ECM of the epidermis is the basement membrane, and collagen and other dermal components constitute the ECM of the dermis. There is significant variation in the composition of the ECM of the epidermis and dermis, which can affect "cell to cell" and "cell to ECM" interactions. These interactions, in turn, can influence biological responses, aging, and wound healing; abnormal ECM signaling likely contributes toskin diseases. Thus, strategies for manipulating cellECM interactions are critical for treating wounds and a variety of skin diseases. Many of these strategies focus on epidermal stem cells, which reside in a unique niche in which the ECM is the most important component; interactions between the ECM and epidermal stem cells play a major role in regulating stem cell fate. As they constitute a major portion of the ECM, it is likely that integrins and type Ⅳ collagens are important in stem cell regulation and maintenance. In this review, we highlight recent research-including our previous work-exploring the role that the ECM and its associated components play in shaping the epidermal stem cell niche.  相似文献   

8.
9.
The transforming growth factor(TGF)-βsignaling pathway controls many cellular processes,including proliferation,differentiation,and apoptosis.Abnormalities in the TGF-βsignaling pathway and its components are closely related to the occurrence of many human diseases,including cancer.Mothers against decapentaplegic homolog 4(Smad4),also known as deleted in pancreatic cancer locus 4,is a typical tumor suppressor candidate gene locating at q21.1 of human chromosome 18 and the common mediator of the TGF-β/Smad and bone morphogenetic protein/Smad signaling pathways.It is believed that Smad4 inactivation correlates with the development of tumors and stem cell fate decisions.Smad4 also interacts with cytokines,miRNAs,and other signaling pathways,jointly regulating cell behavior.However,the regulatory function of Smad4 in tumorigenesis,stem cells,and drug resistance is currently controversial.In addition,Smad4 represents an attractive therapeutic target for cancer.Elucidating the specific role of Smad4 is important for understanding the mechanism of tumorigenesis and cancer treatment.Here,we review the identification and characterization of Smad4,the canonical TGF-β/Smad pathway,as well as the multiple roles of Smad4 in tumorigenesis,stem cells,and drug resistance.Furthermore,we provide novel insights into the prospects of Smad4-targeted cancer therapy and the challenges that it will face in the future.  相似文献   

10.
WU Li 《微生物与感染》2011,6(3):129-132
Human immunodeficiency virus type 1(HIV-1) persistence is a major barrier to the successful treatment and eradication of acquired immunodeficiency syndrome(AIDS).In addition to resting CD4+ T cells,a significant long-lived compartment of HIV-1 infection in vivo includes blood monocytes and tissue macrophages.Studying HIV-1 persistence in monocyte-lineage cells is critical because these cells are important HIV-1 target cells in vivo.Monocyte-lineage cells,including monocytes,dendritic cells(DCs) and macrophages,play a significant role in HIV-1 infection and transmission.These cells have been implicated as viral reservoirs that facilitate HIV-1 latency and persistence.A better understanding of HIV-1 interactions with monocyte-lineage cells can potentially aid in the development of new approaches for intervention.This minireview highlights the latest advances in understanding the role of monocyte-lineage cells in HIV-1 persistence and emphasizes new insights into the mechanisms underlying viral persistence.  相似文献   

11.
Teeth develop as ectodermal appendages from epithelial and mesenchymal tissues. Tooth organogenesis is regulated by an intricate network of cell-cell signaling during all steps of development. The dental hard tissues, dentin, enamel, and cementum, are formed by unique cell types whose differentiation is intimately linked with morphogenesis. During evolution the capacity for tooth replacement has been reduced in mammals, whereas teeth have acquired more complex shapes. Mammalian teeth contain stem cells but they may not provide a source for bioengineering of human teeth. Therefore it is likely that nondental cells will have to be reprogrammed for the purpose of clinical tooth regeneration. Obviously this will require understanding of the mechanisms of normal development. The signaling networks mediating the epithelial-mesenchymal interactions during morphogenesis are well characterized but the molecular signatures of the odontogenic tissues remain to be uncovered.  相似文献   

12.
Epithelial tissues emerge from coordinated sequences of cell renewal, specialization and assembly. Like corresponding immature tissues, adult epithelial tissues are provided by stem cells which are responsible for tissue homeostasis. Advances in epithelial histogenesis has permitted to clarify several aspects related to stem cell identification and dynamics and to understand how stem cells interact with their environment, the so-called stem cell niche. The development and maintenance of epithelial tissues involves epithelial-mesenchymal signalling pathways and cell-matrix interactions which control target nuclear factors and genes. The tooth germ is a prototype for such inductive tissue interactions and provides a powerful experimental system for the study of genetic pathways during development. Clonogenic epithelial cells isolated from developing as well mature epithelial tissues has been used to engineer epithelial tissue-equivalents, e.g. epidermal constructs, that are used in clinical practise and biomedical research. Information on molecular mechanisms which regulate epithelial histogenesis, including the role of specific growth/differentiation factors and cognate receptors, is essential to improve epithelial tissue engineering.  相似文献   

13.
Recent advances in molecular and developmental genetics have provided tools for understanding evolutionary changes in the nature of the epithelial-mesenchymal interactions regulating the patterned outgrowth of the tooth primordia. Tissue recombination experiments in mice have identified the oral epithelium as providing the instructive information for the initiation of tooth development. Teeth were lost in birds for more than 80 million years ago, but despite their disappearance, a number of gene products and the requisite tissue interactions needed for tooth formation are found in the avian oral region. It is believed that the avian ectomesenchyme has lost the odontogenic capacity, whilst the oral epithelium retains the molecular signaling required to induce odontogenesis. In order to investigate the odontogenic capacity of the neural crest-derived mesenchyme and its potential activation of the avian oral epithelium, we have realized mouse neural tube transplantations to chick embryos to replace the neural crest cells of chick with those of mouse. Teeth are formed in the mouse/chick chimeras, indicating that timing is critical for the acquisition of the odontogenic potential by the epithelium and, furthermore, suggesting that odontogenesis is initially directed by species-specific mesenchymal signals interplaying with common epithelial signals.  相似文献   

14.
15.
Tooth-related diseases and tooth loss are widespread and are a major public health issue. The loss of teeth can affect chewing, speech, appearance and even psychology. Therefore, the science of tooth regeneration has emerged, and attention has focused on tooth regeneration based on the principles of tooth development and stem cells combined with tissue engineering technology. As undifferentiated stem cells in normal tooth tissues, dental mesenchymal stem cells (DMSCs), which are a desirable source of autologous stem cells, play a significant role in tooth regeneration. Researchers hope to reconstruct the complete tooth tissues with normal functions and vascularization by utilizing the odontogenic differentiation potential of DMSCs. Moreover, DMSCs also have the ability to differentiate towards cells of other tissue types due to their multipotency. This review focuses on the multipotential capacity of DMSCs to differentiate into various tissues, such as bone, cartilage, tendon, vessels, neural tissues, muscle-like tissues, hepatic-like tissues, eye tissues and glands and the influence of various regulatory factors, such as non-coding RNAs, signaling pathways, inflammation, aging and exosomes, on the odontogenic/osteogenic differentiation of DMSCs in tooth regeneration. The application of DMSCs in regenerative medicine and tissue engineering will be improved if the differentiation characteristics of DMSCs can be fully utilized, and the factors that regulate their differentiation can be well controlled.  相似文献   

16.
Mammalian tooth development relies heavily on the reciprocal and sequential interactions between cranial neural crest-derived mesenchymal cells and stomadial epithelium. During mouse tooth development, odontogenic potential, that is, the capability to direct an adjacent tissue to form a tooth, resides in dental epithelium initially, and shifts subsequently to dental mesenchyme. Recent studies have shown that mouse embryonic dental epithelium possessing odontogenic potential is able to induce the formation of a bioengineered tooth crown when confronted with postnatal mesenchymal stem cells of various sources. Despite many attempts, however, postnatal stem cells have not been used successfully as the epithelial component in the generation of a bioengineered tooth. We show here that epithelial sheets of cultured human keratinocytes, when recombined with mouse embryonic dental mesenchyme, are able to support tooth formation. Most significantly, human keratinocytes, recombined with mouse embryonic dental mesenchyme in the presence of exogenous FGF8, are induced to express the dental epithelial marker PITX2 and differentiate into enamel-secreting ameloblasts that develop a human-mouse chimeric whole tooth crown. We conclude that in the presence of appropriate odontogenic signals, human keratinocytes can be induced to become odontogenic competent; and that these are capable of participating in tooth crown morphogenesis and differentiating into ameloblasts. Our studies identify human keratinocytes as a potential cell source for in vitro generation of bioengineered teeth that may be used in replacement therapy.  相似文献   

17.
18.
The murine tooth development is governed by sequential and reciprocal epithelial-mesenchymal interactions. Multiple signaling molecules are expressed in the developing tooth germ and interact each other to mediate the inductive tissue interactions. Among them are Sonic hedgehog (SHH), Bone Morphogenetic Protein-2 (BMP2) and Bone Morphogenetic Protein-4 (BMP4). We have investigated the interactions between these signaling molecules during early tooth development. We found that the expression of Shh and Bmp2 is downregulated at E12.5 and E13.5 in the dental epithelium of the Msx1 mutant tooth germ where Bmp4 expression is significantly reduced in the dental mesenchyme. Inhibition of BMP4 activity by noggin resulted in repression of Shh and Bmp2 in wild-type dental epithelium. When implanted into the dental mesenchyme of Msx1 mutants, beads soaked with BMP4 protein were able to restore the expression of both Shh and Bmp2 in the Msx1 mutant epithelium. These results demonstrated that mesenchymal BMP4 represents one component of the signal acting on the epithelium to maintain Shh and Bmp2 expression. In contrast, BMP4-soaked beads repressed Shh and Bmp2 expression in the wild-type dental epithelium. TUNEL assay indicated that this suppression of gene expression by exogenous BMP4 was not the result of an increase in programmed cell death in the tooth germ. Ectopic expression of human Bmp4 to the dental mesenchyme driven by the mouse Msx1 promoter restored Shh expression in the Msx1 mutant dental epithelium but repressed Shh in the wild-type tooth germ in vivo. We further demonstrated that this regulation of Shh expression by BMP4 is conserved in the mouse developing limb bud. In addition, Shh expression was unaffected in the developing limb buds of the transgenic mice in which a constitutively active Bmpr-IB is ectopically expressed in the forelimb posterior mesenchyme and throughout the hindlimb mesenchyme, suggesting that the repression of Shh expression by BMP4 may not be mediated by BMP receptor-IB. These results provide evidence for a new function of BMP4. BMP4 can act upstream to Shh by regulating Shh expression in mouse developing tooth germ and limb bud. Taken together, our data provide insight into a new regulatory mechanism for Shh expression, and suggest that this BMP4-mediated pathway in Shh regulation may have a general implication in vertebrate organogenesis.  相似文献   

19.
I Thesleff 《Ontogenez》1989,20(4):341-349
A series of reciprocal interactions between epithelial and mesenchymal tissues control the morphogenesis and cell differentiation in the developing tooth. The molecular mechanisms operating in these interactions are, however, unknown at present. Structural components of the extracellular matrix (ECM) affect cellular behavior in the embryo and appear to be involved also in these regulatory processes. The ECM molecules exert their effects on cells through binding to specific matrix receptors on the cell surface. This review article summarizes our findings on the distribution patterns during tooth development of the ECM glycoproteins, fibronectin and tenascin, and of the cell surface proteoglycan, syndecan, which functions as a receptor for interstitial matrix. Based on the observed changes in these distribution patterns and on experimental evidence, roles for these molecules in epithelial-mesenchymal interactions during tooth development are suggested. Fibronectin and tenascin are enriched in the dental basement membrane at the time of odontoblast differentiation. These matrix glycoproteins may be involved in the cell-matrix interaction which controls differentiation of the dental mesenchymal cells into odontoblasts. Tenascin and syndecan are accumulated in the dental mesenchyme during bud stage of development. We have shown in tissue recombination experiments that the presumptive dental epithelium induces the expression of tenascin and syndecan in mesenchyme. We suggest that these molecules are involved in cell-matrix interactions, which regulate mesenchymal cell condensation during the earliest stages of tooth morphogenesis.  相似文献   

20.
人表皮干细胞(human keratinocyte stem cells,hKSCs)可作为上皮源性的成体干细胞应用于牙齿再生,但是其诱导效率较低.本研究利用小分子化合物CHIR-99021提高hKSCs的Wnt/β-catenin信号活性,再与具有诱导成牙潜能的小鼠牙胚间充质重组,构建嵌合体,并移植裸鼠肾囊膜下培养20 d.将嵌合体组织切片,并利用组织染色和免疫组化等方法鉴定牙齿结构.结果显示,经FGF8诱导处理的hKSCs与小鼠牙胚间充质构成的嵌合体的成牙率为27.80%,其中成釉率仅为40.00%;经CHIR-99021诱导处理的hKSCs与小鼠牙胚间充质构成的嵌合体的成牙率仅为18.20%,其中成釉率高达100%;而CHIR-99021与FGF8协同作用,则进一步提高嵌合体成牙率至40.00%,其中成釉率也达75.00%.进一步的研究发现,经CHIR-99021处理后,hKSCs的Wnt/β-catenin信号活性明显提高,同时FGF8的表达水平也显著上调.以上结果表明,CHIR-99021可通过上调Wnt/β-catenin信号活性水平,同时促进FGF8表达,与FGF8协同,高效诱导hKSCs分化为具有分泌釉质功能的成釉质细胞.研究结果对利用hKSCs作为上皮来源的成体细胞应用于人类牙齿再生的研究具有重要意义.  相似文献   

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