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 are easier to derive than human embryonic stem cells, are largely free of ethical problems, and have enabled a major expansion in. Induced pluripotent stem cells ipscs hold great promise in. Whether differentiation of induced pluripotent stem cells ipscs in ischemic myocardium enhances their immunogenicity, thereby increasing their chance for rejection, is unclear. Immunogenicity of induced pluripotent stem cells nature. The potential and limitations of induced pluripotent stem cells to. Induced pluripotent stem cells ipscs, reprogrammed from somatic cells with defined factors, hold great promise for regenerative medicine as. Low immunogenicity of mouse induced pluripotent stem cell. Induced pluripotent stem cells display several genetic and epigenetic abnormalities that could promote tumorigenicity and immunogenicity in vivo. Creative commons attribution license ccby for citation purposes. Induced pluripotent stem cells ipsc are an exciting cell type with enhanced therapeutic and translational potential. Induced pluripotent stem cells ipscs 8,9 are a potential cell source for all cell types, including chondrocytes. 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. Pdf immunogenicity of induced pluripotent stem cells.
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. Pdf induced pluripotent stem cells and their implication for. We found that the injection of ipscs derived from different ages of mice into syngeneic c57bl6 mice produced teratoma and was not. With clinical trials on the horizon, it is imperative that the immunogenicity of hescs and ipscs be definitively understood.
Cells within teratomas formed by hipscs can be immunogenic in humice. The promise of induced pluripotent stem cells ipscs. 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 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. Humanized mice reveal differential immunogenicity of. Generation and applications of induced pluripotent stem. Jci hurdles to clinical translation of human induced. Inherent immunogenicity or lack thereof of 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. 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. Slideshare uses cookies to improve functionality and performance, and to provide you with relevant advertising.
The potential for immunogenicity of autologous induced. Diabetes mellitus is caused by the death or dysfunction of insulinproducing. The potential and limitations of induced pluripotent stem. Induced pluripotent stem cells in medicine and biology.
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. Immunogenicity and tumorigenicity of human pluripotent. 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. Low immunogenicity of mouse induced pluripotent stem cellderived neural stemprogenitor cells. 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. Molecular imaging of induced pluripotent stem cell. 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. 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. Human ipscderived neural crest stem cells exhibit low.
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. Hscs can be generated from induced pluripotent stem cells ipscs, which requires the understanding of the. Murine ipscs were transduced with a trifusion tf reporter gene consisting of. It is generally assumed that cells derived from autologous ipscs will be immune privileged. Pluripotent stem cells an overview sciencedirect topics. Human induced pluripotent stem cells hipscs have potential applications in cell replacement therapy and regenerative medicine. A highefficiency system for the generation and study of human induced pluripotent stem cells. Differentiated cells can be reprogrammed to pluripotency and other cell fates by treatment with defined factors. These cells were termed induced pluripotent stem cells ipscs. Induced pluripotent stem cells ipsc are an exciting cell type with. While generation of ipscs represents a significant breakthrough, the clinical relevance of ipscs for cellbased therapies requires generation of highquality specialized 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. To investigate functional immunogenicity, we used ipscncscs as stimulator. Damaged cartilage can be repaired with celltissue sources that are transplanted, however, autologous chondrocytes are limited in number as a cell source.
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. 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. 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. If you continue browsing the site, you agree to the use of cookies on this website.
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. 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. Induced pluripotent stem cells genetics and genomics. The ipscs show unlimited growth while maintaining their.
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. Immunogenicity of induced pluripotent stem cells request pdf. This differential immunogenicity is due in part to abnormal expression of immunogenic antigens. 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. 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. Maherali n, ahfeldt t, rigamonti a, utikal j, cowan c, hochedlinger k. Negligible immunogenicity of induced pluripotent stem. This approach circumvented the usual ethical problems associated with escs and raised the possibility of. The result of this transient overexpression is demethylation of the genome, an epigenetic reprogramming that opens up the ipsc to development programs. 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. 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.
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. These issues could be circumvented by the derivation of mscs from pluripotent stem cells. The discovery of induced pluripotent stem cells ipscs has opened up unprecedented opportunities in the pharmaceutical industry, in the clinic and in laboratories. Therefore, human pscs hold great promise for regenerative medicine. Cardiac repair in guinea pigs with human engineered heart. However, the immunogenicity of autologous human ipsc hipscderived cells is not well understood. Here, we dynamically demonstrated the immunogenicity and rejection of ipscs in ischemic myocardium using bioluminescent imaging bli. 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. Negligible immunogenicity of induced pluripotent stem cells. Induced pluripotent stem cell ipsc technology offers the promise of immunematched cellular therapies for a wide range of diseases and injuries. Whereas it has been generally assumed that these autologous cells should be immunetolerated by the recipient from whom the ipscs are derived, their. 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. A heart attack destroys cardiac muscle, resulting in a fibrotic scar.
Immunogenicity of induced pluripotent stem cells circulation. The immunogenicity of cells derived from induced pluripotent stem. Immunogenicity and tumorigenicity of human pluripotent stem cells. Immunogenicity of pluripotent stem cells and their. Ipscderived neural crest stem cells ncscs have significant potential. Humanized mice reveal differential immunogenicity of cells. The breakthrough of induced pluripotent stem cell ipsc technology has raised the possibility. The immunogenicity of induced pluripotent stem cells ipscderived teratomas. Hematopoietic stem cells from induced pluripotent stem. These factors were chosen because they were known to be involved in the maintenance. These threedimensional strips were placed over injured areas of guinea pig hearts.
Recent clinical trials are evaluating induced pluripotent stem cells ipscs as a cellular therapy in the field of regenerative medicine. Induced pluripotent stem cells ipscs open the great possibility to employ patients own tissue to the previously incurable diseases. Pluripotent stem cells hold significant promise for the treatment of tissue deficiencies and other human diseases 1, 2. The immunogenicity and immune tolerance of pluripotent.
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. What are induced pluripotent stem cells or ips cells. Induced pluripotent stem cells ipscs are created from more differentiated cells by transient overexpression of genes normally expressed only in pluripotent scs. Hence, it is crucial to understand the effect of these abnormalities on the immunogenicity and survival of psc grafts. Mouse clone model for evaluating the immunogenicity and. Immunogenicity and tumorigenicity of 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. Liu x, li w, fu x and xu y 2017 the immunogenicity and immune tolerance of pluripotent stem cell derivatives. Induced pluripotent stem cells ipscs collection 2019. The breakthrough of induced pluripotent stem cell ipsc technology has raised the possibility that. In vitro immunogenicity of undifferentiated pluripotent. The immunogenicity and immune tolerance of pluripotent stem cell.
No immunogenicity of ips cells in syngeneic host studied. 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. 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. 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. To learn more about ips cells watch what are induced pluripotent stem cells. In vivo directed differentiation of pluripotent stem cells. However these cells can be used in cell therapy only if they are not rejected when transplanted back into the syngeneic host. The promise of induced pluripotent stem cells ipscs potentially more efficient integrative approaches. Donorspecific induced pluripotent stem cells ipscs offer opportunities for personalized cell replacement therapeutic approaches due to their. Limited immunogenicity of human induced pluripotent stem.
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