These factors were chosen because they were known to be involved in the maintenance. Induced pluripotent stem cells ipscs, reprogrammed from somatic cells with defined factors, hold great promise for regenerative medicine as. Immunogenicity and tumorigenicity of human pluripotent stem cells. Hence, it is crucial to understand the effect of these abnormalities on the immunogenicity and survival of psc grafts. The discovery of reprogramming and generation of humaninduced pluripotent stem cells ipscs has revolutionized the field of regenerative medicine and opened new opportunities in cell replacement therapies. Induced pluripotent stem cell ipsc technology offers the promise of immunematched cellular therapies for a wide range of diseases and injuries. Immunogenicity of induced pluripotent stem cells nature. The reprogramming of somatic cells into pluripotent stem cells has been reported after introducing a combination of several defined factors, such as oct34, sox2, klf4, and cmyc, into the cells. Murine ipscs were transduced with a trifusion tf reporter gene consisting of. Induced pluripotent stem cells ipscs open the great possibility to employ patients own tissue to the previously incurable diseases. Immunogenicity of induced pluripotent stem cells request pdf. Recent clinical trials are evaluating induced pluripotent stem cells ipscs as a cellular therapy in the field of regenerative medicine.
No immunogenicity of ips cells in syngeneic host studied. This approach circumvented the usual ethical problems associated with escs and raised the possibility of. Pluripotent stem cells hold significant promise for the treatment of tissue deficiencies and other human diseases 1, 2. Here, we dynamically demonstrated the immunogenicity and rejection of ipscs in ischemic myocardium using bioluminescent imaging bli. Differentiated cells can be reprogrammed to pluripotency and other cell fates by treatment with defined factors. To investigate the immunerejection and tumorformation potentials of induced pluripotent stem cells and other stem cells, we devised a modeldesignated the mouse clone modelwhich combined the theory of somatic animal cloning, tetraploid complementation, and induced pluripotent stem cells to demonstrate the applicability of stem cells for transplantation therapy. Pluripotent stem cells an overview sciencedirect topics. With clinical trials on the horizon, it is imperative that the immunogenicity of hescs and ipscs be definitively understood.
Immunogenicity and tumorigenicity of pluripotent stem. Immunogenicity of pluripotent stem cells and their. The discovery of induced pluripotent stem cells ipscs has opened up unprecedented opportunities in the pharmaceutical industry, in the clinic and in laboratories. The breakthrough of induced pluripotent stem cell ipsc technology has raised the possibility. If you continue browsing the site, you agree to the use of cookies on this website. Damaged cartilage can be repaired with celltissue sources that are transplanted, however, autologous chondrocytes are limited in number as a cell source. Ipscderived neural crest stem cells ncscs have significant potential. The promise of induced pluripotent stem cells ipscs potentially more efficient integrative approaches.
The recent breakthrough in the generation of induced pluripotent stem cells ipscs by reprogramming somatic cells with defined factors has raised the hope that ipscs, which are identical to human embryonic stem cells hescs in the context of pluripotency, could become a renewable source of autologous cells for transplantation into human patients. Jci hurdles to clinical translation of human induced. Derivation of induced pluripotent stem cells ipscs from patients followed by differentiation into diseaserelevant cell types holds great promise for in vitro disease modeling, drug screening, and autologous cell replacement therapy for multiple diseases 1, 2. To investigate functional immunogenicity, we used ipscncscs as stimulator. It is generally assumed that cells derived from autologous ipscs will be immune privileged. Immunogenicity of induced pluripotent stem cells circulation. To learn more about ips cells watch what are induced pluripotent stem cells. Induced pluripotent stem cells ipscs, reprogrammed from somatic cells with defined factors, hold great promise for regenerative medicine as the renewable source of autologous cells 1,2,3,4,5. We found that the injection of ipscs derived from different ages of mice into syngeneic c57bl6 mice produced teratoma and was not. Cardiac repair in guinea pigs with human engineered heart. Immunogenicity and tumorigenicity of human pluripotent. The generation of induced pluripotent stem cells ipscs from somatic cells demonstrated that adult mammalian cells can be reprogrammed to a pluripotent state by the enforced expression of a few embryonic transcription factors. The potential clinical applications of the more primitive embryonic stem cells escs and induced pluripotent stem cells ipscs have so far been discouraging, as both have exhibited several. The potential and limitations of induced pluripotent stem cells to.
The breakthrough of induced pluripotent stem cell ipsc technology has raised the possibility that. Therefore, human pscs hold great promise for regenerative medicine. The potential and limitations of induced pluripotent stem. Liu x, li w, fu x and xu y 2017 the immunogenicity and immune tolerance of pluripotent stem cell derivatives.
Induced pluripotent stem cells ipsc are an exciting cell type with. Human induced pluripotent stem cells ipscs have been proposed as a potential source of autologous stem cells for therapy, but even these autologous stem cells may be targets of immune rejection. Induced pluripotent stem cells ipscs hold great promise in. A heart attack destroys cardiac muscle, resulting in a fibrotic scar. Inherent immunogenicity or lack thereof of pluripotent stem cells. On the other hand, embryonic stem cells escs and newly found type of stem cell, induced pluripotent stem cells ipscs, encounter major impediments to clinical therapeutic trials bongso and. Whereas it has been generally assumed that these autologous cells should be immunetolerated by the recipient from whom the ipscs are derived, their. What are induced pluripotent stem cells or ips cells. Scientists immediately recognized that these induced pluripotent stem cells ipscs 2 represent a potential source of autologous cell therapies that could avoid the issues of immunogenicity associated with allogeneic sources such as human embryonic stem cells hescs or donated tissue 3. One key advantage of ipscs for human cell therapy is that patientspecific ipscs are autologous, and, therefore, it has been assumed that the cells derived from them can be transplanted into the same patient without concerns over immune rejection. Recently, the suitability of induced pluripotent stem cells applied for patienttailored cell therapy has been questioned since the discovery of several genetic and epigenetic aberrations during the reprogramming process. Creative commons attribution license ccby for citation purposes. Hscs can be generated from induced pluripotent stem cells ipscs, which requires the understanding of the.
Humanized mice reveal differential immunogenicity of cells. While the discovery of ips cells was a very important development, more research needs to be done to discover if they will offer the same research value as embryonic stem cells and if they will be as useful for therapy. Induced pluripotent stem cells ipscs collection 2019. The immunogenicity and immune tolerance of pluripotent stem cell. Low immunogenicity of mouse induced pluripotent stem cellderived neural stemprogenitor cells. However, the immunogenicity of autologous human ipsc hipscderived cells is not well understood. While generation of ipscs represents a significant breakthrough, the clinical relevance of ipscs for cellbased therapies requires generation of highquality specialized cells. Whether differentiation of induced pluripotent stem cells ipscs in ischemic myocardium enhances their immunogenicity, thereby increasing their chance for rejection, is unclear. Induced pluripotent stem cells genetics and genomics. Diabetes mellitus is caused by the death or dysfunction of insulinproducing. Induced pluripotent stem cells are easier to derive than human embryonic stem cells, are largely free of ethical problems, and have enabled a major expansion in.
Pluripotent stem cells pscs, including human embryonic stem cells hescs and induced pluripotent stem cells ipscs, are capable of unlimited selfrenewal and differentiating into all types of cells. Understanding the persistence and effects of these abnormalities in induced pluripotent stem cell derivatives is critical to allow clinicians to predict graft fate after transplantation, and to take. Donorspecific induced pluripotent stem cells ipscs offer opportunities for personalized cell replacement therapeutic approaches due to their. Negligible immunogenicity of induced pluripotent stem. The ipscs show unlimited growth while maintaining their.
Induced pluripotent stem cells also known as ips cells or ipscs are a type of pluripotent stem cell that can be generated directly from adult cells. Induced pluripotent stem cells ipscs collection 2019 pluripotent stem cells remain at the cutting edge of research with fascinating new molecular insights and promising treatment approaches being reported at an everaccelerating pace. Limited immunogenicity of human induced pluripotent stem. Both human induced pluripotent stem cells hipscs and embryonic stem cells hescs are capable of differentiating into a multitude of cell types from each of three germ layers, allowing investigators to devise novel platforms for research and therapeutic drug screening 3. Low immunogenicity of mouse induced pluripotent stem cell. Induced pluripotent stem cells ipscs are a relatively new and abundant cell source and can be made from the patient, but at a considerable cost. Slideshare uses cookies to improve functionality and performance, and to provide you with relevant advertising. These issues could be circumvented by the derivation of mscs from pluripotent stem cells.
In 2006 and 2007, takahashi and yamanaka made landmark discoveries in mouse and human induced pluripotent stem cells ipscs, respectively, with the introduction of only four transcription factors, namely oct4, sox2, klf4, and cmyc 5, 6. In this study, expression of mhc and t cell costimulatory molecules in hipscs, and the effects on activation, proliferation and cytokine production in allogeneic human peripheral. Although hematopoietic stem cell hsc therapy for hematological diseases can lead to a good outcome from the clinical point of view, the limited number of ideal donors, the comorbidity of patients and the increasing number of elderly patients may limit the application of this therapy. The immunogenicity and immune tolerance of pluripotent. Mouse clone model for evaluating the immunogenicity and. Human induced pluripotent stem cells hipscs have potential applications in cell replacement therapy and regenerative medicine. The breakthrough of induced pluripotent stem cell ipsc technology has raised the possibility that patientspecific ipscs may become a renewable source of autologous cells for cell therapy without the concern of immune rejection. Pdf induced pluripotent stem cells and their implication for. This differential immunogenicity is due in part to abnormal expression of immunogenic antigens. Humanized mice reveal differential immunogenicity of.
Induced pluripotent stem cells ipscs, reprogrammed from somatic cells with defined factors, hold great promise for regenerative medicine as the renewable source of autologous cells. The observation that embryonic stem cells escs expressed reduced levels of major histocompatibility mhc class i genes, no mhc class ii or costimulatory molecules suggested early on that pluripotent stem cells pscs could be immuneprivileged and were unable to. In vivo directed differentiation of pluripotent stem cells. Pluripotent stem cells represent an attractive alternative to tissue specific stem cells as they have unlimited proliferation capacity and the ability to differentiate into all somatic cell lineages. Induced pluripotent stem cells in medicine and biology. The potential for immunogenicity of autologous induced. Induced pluripotent stem cells ipscs are created from more differentiated cells by transient overexpression of genes normally expressed only in pluripotent scs. Recently, the usage of autologous pluripotent stem cells for transplantation became conceivable by description of induced pluripotent stem cells ipscs and multipotent adult germline stem cells magscs. Induced pluripotent stem cells display several genetic and epigenetic abnormalities that could promote tumorigenicity and immunogenicity in vivo. In vitro immunogenicity of undifferentiated pluripotent. Induced pluripotent stem cells ipsc are an exciting cell type with enhanced therapeutic and translational potential. Human pluripotent stem cells were first described in 1998 when james thomson and colleagues isolated embryonic stem es cells from the inner cell mass of blastocyst stage human embryos. The ipsc technology was pioneered by shinya yamanakas lab in kyoto, japan, who showed in 2006 that the introduction of four specific genes encoding transcription factors could convert adult cells into pluripotent stem cells. Maherali n, ahfeldt t, rigamonti a, utikal j, cowan c, hochedlinger k.
Pdf immunogenicity of induced pluripotent stem cells. A highefficiency system for the generation and study of human induced pluripotent stem cells. The widespread clinical utility of ipscs is expected to be realized using allogeneic cells that have undergone thorough safety evaluations, including assessment of their immunogenicity. However, limited information is available regarding the immunologic features of ipscs. The immunogenicity of cells derived from induced pluripotent stem. Molecular imaging of induced pluripotent stem cell. The result of this transient overexpression is demethylation of the genome, an epigenetic reprogramming that opens up the ipsc to development programs. The promise of induced pluripotent stem cells ipscs. Human ipscderived neural crest stem cells exhibit low. These threedimensional strips were placed over injured areas of guinea pig hearts. Negligible immunogenicity of induced pluripotent stem cells. Resolving the immunogenicity of cells derived from induced pluripotent stem cells ipscs remains an important challenge for cell transplant strategies that use banked allogeneic cells. Induced pluripotent stem cells ipscs 8,9 are a potential cell source for all cell types, including chondrocytes. Generation and applications of induced pluripotent stem.
These cells were termed induced pluripotent stem cells ipscs. However these cells can be used in cell therapy only if they are not rejected when transplanted back into the syngeneic host. Cells within teratomas formed by hipscs can be immunogenic in humice. The immunogenicity of induced pluripotent stem cells ipscderived teratomas. Hematopoietic stem cells from induced pluripotent stem.
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