Differentiation of stem cells into mature cells through the use of physical approaches is of great interest. Transcription factorinduced reprogramming of specialized cells into other cell types and to pluripotency has revolutionized our thinking about cell plasticity, differentiation, and stem cells. For example, the yamanaka factors pou5f1, sox2, klf4 and myc oskm can reprogram somatic cells into induced pluripotent stem cells ipscs takahashi and. Novel approaches to transdifferentiation cloning and stem cells. Solid tumors exhibit diverse patterns of neovascularization, including sprouting angiogenesis, vasculogenesis, intussusception, vessel cooption, vascular.
Transdifferentiation of adiposederived stem cells into. Human mesenchymal stem cells mscs are good candidates for brain cell replacement strategies and have already been used as adjuvant treatments in neurological disorders. Moreover, ips cells are often karyotypically unstable when grown in feeder free. Transdifferentiation note cards questions and study guide. Using techniques like potency reprogramming or switch lineages. A list of examples of in vivo transdifferentiation through transfection. Nov 24, 2015 first, cell fusion of cancer cells, epithelial cells or stem cells with bmdcs, especially macrophages, is a common event in tumorigenesis and metastasis. Pdf differentiation and transdifferentiation potentials of. In a variation of transdifferentiation experiments, scientists have. Cancer stem cells not all the cells within a tumor can maintain tumor growth, most cancers are not clonal. Transdifferentiation lineage reprogramming, or conversion, is a process in which one mature. The discovery of novel drugs for neurodegenerative diseases has been a real challenge over the last decades.
Transdifferentiation of human endothelial progenitors into. Differentiation and transdifferentiation potentials of cancer stem cells article pdf available in oncotarget 637 october 2015 with 756 reads how we measure reads. Here, we prepared smart nanoenvironments by cellimprinted substrates based on. Transdifferentiation an overview sciencedirect topics. The transdifferentiating potential of stem cells varies with source and according to that. Pdf transdifferentiation is defined as the conversion of one cell type to another. In adult organisms, stem cells and progenitor cells act as a repair system for the body, replenishing adult tissues. Studies of neural transdifferentiation of mscs can be divided into two groups, namely in vitro studies 10, 11, 1418, 20, 21 and transplantation studies 8, 9, 12, 19. The success of these studies, the cloning of dolly, and more current studies involving adult stem cells and transdifferentiation provide us with a large repository of potential candidate molecules and experimental systems that will assist in the generation of safe, transgene free pluripotential cells. Jan 21, 2011 by contrast, neural stem cells can be effectively reprogrammed using just oct4. Several longknown oncogenic pathways are pivotal to the maintenance of normal stem cell selfrenewal. Transdifferentiation of human adult peripheral blood t cells. Previously unknown possibilities of cell differentiation beyond the known commitment of a given stem cell have been described using keywords such as. Pdf dedifferentiation, transdifferentiation and reprogramming.
Stem cells for generation and regeneration of retinal neurons in teleost fish jenny r. Transdifferentiation, conversion of one differentiated mature cell type into another cell type. Similar transdifferentiation has resulted in induced neuron in cells, also by introducing 3 tissuespecific transcription factors 6. Stem cell and transdifferentiation study literatures. The inhibition of line1 elements impairs the transdifferentiation potential of mef cells. Because similar signaling pathways are activated by damageassociated molecular patterns, epigenetic plasticity induced by innate immunity may play a fundamental role in transdifferentiation during wound healing and regeneration.
Because similar signaling pathways are activated by. Successful transdifferentiation from one cell type to. Research open access transdifferentiation of malme3m. Stem cells ipscs applications in regenerative medicine. In some cases transdifferentiation is a onestep process, while in others the cells pass through an intermediate state, as shown in a study to reprogram b cells into macrophages where the cells express low levels of both b cellspecific genes and macrophagespecific genes before they completely transdifferentiate into macrophages. Skin regeneration is an important area of research in the field of tissueengineering, especially for cases involving loss of massive areas of skin, where current treatments are not capable of. Transdifferentiation, metaplasia and tissue regeneration ncbi. In vitro transdifferentiation of human adipose tissuederived stem cells to neural lineage cells a stagespecific incidence subathra radhakrishnan a,b, omana anna trentz c, mettu srinivas reddy a,d, mohamed rela a,d. Transdifferentiation versus stem cell hypothesis for the. Jun 05, 2019 dedifferentiation, transdifferentiation and reprogramming. What can transdifferentiation and nuclear reprogramming teach us about ips cell generation. Nov 24, 2004 embryonic stem es cells are normally derived from the inner cell mass of the blastocyst, and are pluripotent i. Transdifferentiation, metaplasia and tissue regeneration. By contrast, the fate of stem cells, which exist in an undifferentiated state, is more difficult to.
Neural transdifferentiation of mesenchymal stem cells a. However, ips cells have significant linetoline variability in terms of differentiation capacity, presumably due to variations in their epigenetic and pluripotent state 57. In vitro transdifferentiation of human adipose tissuederived. Transdifferentiation, also known as lineage reprogramming, is a process in which one mature somatic cell transforms into another mature somatic cell without undergoing an intermediate pluripotent state or progenitor cell type.
Evidence suggests that transdifferentiation of mesenchymal stem cells mscs into various neuronal cells contributes to functional recovery after experimental spinal cord. It is a type of metaplasia, which includes all cell fate switches, including the interconversion of stem cells. It has been demonstrated that pigmented epithelial cells pecs of the lens. The development of patient andor diseasespecific in vitro models represents a powerful strategy for the development and validation of lead candidates in preclinical settings. Reprogramming of adult stem cells for tissue repair and regeneration. To convincingly show transdifferentiation of adult stem cells across lineage boundaries requires stringent experimental criteria such as clonal analyses. The implementation of a reliable platform modeling dopaminergic neurons will be an asset in the study.
Horb, in handbook of stem cells second edition, 20. Transdifferentiation involves reprogramming one type of adult cell into another mature cell type, without having to generate intermediary stem cells. Replating these cells in embryonic stem cell medium confirmed that they were true induced pluripotent stem cells that could be expanded in. Techniques used in the stem cell field have identified selfrenewing cells. The handbook of stem cells, edited by robert lanza and. Pharmacological transdifferentiation of human nasal olfactory.
Pdf stem cell plasticity, cell fusion, and transdifferentiation. In this article, orlando and colleagues show that line1 elements are reactivated and retrotransposed upon transdifferentiation of mef cells into induced dopaminergic neurons. Adult stem cells have been shown to display a broader differentiation potential than anticipated and may contribute to tissues other than those in which they reside. It has been demonstrated that pigmented epithelial cells pecs of the lens regenerate and proliferation can be promoted by neuregulin, an extracellular further differentiate to form a new lens. The classical definition of a stem cell is a type of undifferentiated cell that is both self. If the inline pdf is not rendering correctly, you can. D espite the large amount of literature demonstrating transdifferentiation and cellular. Differentiation and transdifferentiation potentials of cancer. Transdifferentiation of mscs into neurons has aroused considerable interest. Pdf differentiation and transdifferentiation potentials. Recently a large amount of new data on the plasticity of stem cells of various lineages have emerged, providing new perspectives especially for the therapeutic application. Dedifferentiation, transdifferentiation and reprogramming. Transdifferentiation may be achieved in several ways.
Fusion between epithelial cancer cells and macrophages was reported in the intestine, which generates hybrid cells that have the characteristics of cancer cells and macrophages upon nuclear. In this article, orlando and colleagues show that line1 elements are reactivated and retrotransposed upon transdifferentiation of mef cells into induced dopaminergic neurons ida. Organized in two volumes entitled pluripotent stem cells and cell biology and adult and fetal stem cells, this work contains contributions from the worlds experts in stem cell research to provide a description of the tools, methods, and experimental protocols needed to study and characterize stem cells and progenitor populations as well as a. Differentiation and transdifferentiation potentials of. Dedifferentiation, transdifferentiation and cell fusion. Recently our group has published the about obtaining betalikecells from white blood cells by reprogramming blood monocytes in the presence of. Transdifferentiation of nonislet cells to islet cells. Transdifferentiation of human endothelial progenitors into smooth muscle cells hayeun ji a,1, leigh atchison b,1, zaozao chen a, syandan chakraborty a, youngmee jung d, george a. In vitro transdifferentiation of human adipose tissue. In adult organisms, stem cells and progenitor cells act as a repair system for the. During normal development, the only cells with the potential to change lineage identity are uncommitted stem and progenitor cells.
Neural stem cells red derived from female skin cells using a transdifferentiation protocol with yamanaka factors first pass through a pluripotent stem cell state green. Transdifferentiation of human adult peripheral blood t. Some of these cardiogenic progenitors have been reported to contribute replacement muscle through endogenous reparative processes or via cell transplantation in preclinical. Stem cells is read and written by clinical and basic scientists whose expertise encompasses the rapidly expanding fields of stem and progenitor cell biology. Examples of in vivo transdifferentiation by lineage. Thomas graf believes ips system is safer than transdifferentiation one of the first people to differentiate blood cells slide 7 in this view, pluripotent cells ips cells and embryonic stem. Transdifferentiation of cancer stem cells into endothelial cells. Human induced pluripotent stem cells free of vector and transgene sequences. Transdifferentiation of human fibroblasts to endothelial cells. Neuronal transdifferentiation potential of human mesenchymal. The term transdifferentiation was first introduced by selman. In addition, novel transdifferentiation strategies are being developed.
The neogenetic process involves differentiation of duct. Research paper in vitro transdifferentiation of human adipose tissuederived stem cells to neural lineage cells a stagespecific incidence subathra radhakrishnana,b, omana anna. Cardiogenic differentiation and transdifferentiation of. Novel approaches to transdifferentiation cloning and. Transdifferentiation of adult cells into insulinproducing cells also provides another exciting opportunity for. Transdifferentiation occurs naturally in only a few instances of regeneration. These techniques raise high hopes that patientpersonalized cell therapies will become a reality in the notsodistant future. Transdifferentiation of differentiated stem cells contributes. Transdifferentiation of cancer stem cells into endothelial. Most reprogramming studies use heterogeneous fibroblasts as donor cells, raising the question as to whether the transdifferentiation capability is limited to undifferentiated progenitor cells 29. These include pluripotent embryonic stem cells, as well various adult stem cells resident in compartments including bone marrow, peripheral tissues, and the heart itself. By contrast, neural stem cells can be effectively reprogrammed using just oct4. It has received significant attention because it may have a considerable number of applications in cell and cancer therapy. Therefore, it seems that by using defined combinations of tissuespecific transcription factors it is possible to generate cells of different tissue types.
Human adiposederived stem cells asc have been shown to differentiate invitro into both mesenchymal lineages and nonmesenchymal lineages, confirming their. First, we will introduce various regeneration systems in plants and animals, and then discuss the origin of regenerating cells. Jun 19, 2018 during normal development, the only cells with the potential to change lineage identity are uncommitted stem and progenitor cells. Pharmacological transdifferentiation of human nasal. Therefore, it seems that by using defined combinations of. Conclusions this study suggests that manipulation of innate immune signaling may be generally used to modify cell fate. Novel markers for delineation cancer stem cells and inducedpluripotent stem cells. Another route in generating cells of a different cell type is by utilizing transdifferentiation. The ability to convert one cell type into another has caused great excitement in the stem cell field. Research open access transdifferentiation of malme3m and mcf. Growth of microvessels in serumfree matrix culture of rat. The stem cells are located at the crypt base and produce progenitor cells, called transit amplifying cells, that divide a few times before differentiating into one of the four mature cell types van.
Evidence suggests that transdifferentiation of mesenchymal stem cells mscs into various neuronal cells contributes to functional recovery after experimental spinal cord injury. Transdifferentiation is of particular interest in the field of regenerative medicine, since transdifferentiated cells already exist in a mature state, avoiding concerns about the fate of the cells following transplantation into the patient. The recent advances in this area were enabled by the confluence of a number of experimental breakthroughs that took place over the past 60 years. Recent work shows the occurrence of alternative vasculogenic patterns is due to the presence of stem cell population cancer stem cells, csc at least in melanoma and glioblastoma.
Skin regeneration is an important area of research in the field of tissueengineering, especially for cases involving loss of massive areas of skin, where current treatments are not capable of inducing permanent satisfying replacements. Historically, the terms transdifferentiation and metaplasia were introduced to describe different phenomena. Human cell models for disease based on induced pluripotent stem ips cells have proven to. Jul 30, 2015 neural stem cells red derived from female skin cells using a transdifferentiation protocol with yamanaka factors first pass through a pluripotent stem cell state green, indicating xchromosome. Transdifferentiation of human adult peripheral blood t cells into neurons koji tanabea,b,1. Recently a large amount of new data on the plasticity of stem cells of various lineages have emerged, providing new perspectives especially for the therapeutic application of adult stem cells.
On the one hand, morphallatic regeneration involves migration of stem cells to the damage site, where they differentiate into tissue. Pdf transdifferentiation, metaplasia and tissue regeneration. Line1 retrotransposition in postmitotic ida cells is lineage specific and correlates with chromatin opening and lncrna. Several longknown oncogenic pathways are pivotal to the maintenance of normal. Toward transgenefree induced pluripotent stem cells.