Tumor-Free Transplantation of Patient-Derived Induced Pluripotent Stem Cell Progeny for Customized Islet Regeneration

Khatib, Moustafa M. El; Ohmine, Seiga; Jacobus, Egon J.; Tonne, Jason M.; Morsy, Salma G.; Holditch, Sara J.; Schreiber, Claire A.; Uetsuka, Koji; Fusaki, Noemi; Wigle, Dennis A.; Terzic, André; Kudva, Yogish C.; Ikeda, Yasuhiro

doi:10.5966/sctm.2015-0017

Cited by 34 publications

(25 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As summarized in Table , multiple reports describe the generation of iPSCs from patients with diabetes‐related disorders, including types 1 and 2 diabetes mellitus; maturity‐onset diabetes of the young types 1, 2, 3, 5 and 8, in which a single gene mutation causes diabetes; and mitochondria diabetes. A report analyzing maturity‐onset diabetes of the young type 2 showed that iPSC models can reproduce the disease phenotype caused by mutations in a glucokinase gene that cause a decrease in insulin secretion by glucose stimulation.…”

Section: Disease Modeling and Drug Discoverymentioning

confidence: 99%

iPSC technology‐based regenerative therapy for diabetes

Kondo

Toyoda

Inagaki

et al. 2017

J of Diabetes Invest

View full text Add to dashboard Cite

The directed differentiation of human pluripotent stem cells, such as embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs), into pancreatic endocrine lineages has been vigorously examined by reproducing the in vivo developmental processes of the pancreas. Recent advances in this research field have enabled the generation from hESCs/iPSCs of functionally mature β‐like cells in vitro that show glucose‐responsive insulin secretion ability. The therapeutic potentials of hESC/iPSC‐derived pancreatic cells have been evaluated using diabetic animal models, and transplantation methods including immunoprotective devices that prevent immune responses from hosts to the implanted pancreatic cells have been investigated towards the development of regenerative therapies against diabetes. These efforts led to the start of a clinical trial that involves the implantation of hESC‐derived pancreatic progenitors into type 1 diabetes patients. In addition, patient‐derived iPSCs have been generated from diabetes‐related disorders towards the creation of novel in vitro disease models and drug discovery, although few reports so far have analyzed the disease mechanisms. Considering recent advances in differentiation methods that generate pancreatic endocrine lineages, we will see the development of novel cell therapies and therapeutic drugs against diabetes based on iPSC technology‐based research in the next decade.

show abstract

Section: Disease Modeling and Drug Discoverymentioning

confidence: 99%

iPSC technology‐based regenerative therapy for diabetes

Kondo

Toyoda

Inagaki

et al. 2017

J of Diabetes Invest

View full text Add to dashboard Cite

show abstract

“…Before iPSCs can be considered for clinical application newer methods that have been developed using non‐integrating systems must be applied in these species to reduce the risk of the reprogramming factors becoming re‐activated and leading to tumor formation by the cells. Recent work has demonstrated that the generation of mouse iPSCs through non‐integrating methods (along with efficient removal of undifferentiated cells prior to transplantation) reduces the risk of tumor formation .…”

Section: Differentiation Of Companion Animal Pluripotent Cells Into Tmentioning

confidence: 99%

Characterization of companion animal pluripotent stem cells

2017

View full text Add to dashboard Cite

Pluripotent stem cells have the capacity to grow indefinitely in culture and differentiate into derivatives of the three germ layers. These properties underpin their potential to be used in regenerative medicine. Originally derived from early embryos, pluripotent stem cells can now be derived by reprogramming an adult cell back to a pluripotent state. Companion animals such as horses, dogs, and cats suffer from many injuries and diseases for which regenerative medicine may offer new treatments. As many of the injuries and diseases are similar to conditions in humans the use of companion animals for the experimental and clinical testing of stem cell and regenerative medicine products would provide relevant animal models for the translation of therapies to the human field. In order to fully utilize companion animal pluripotent stem cells robust, standardized methods of characterization must be developed to ensure that safe and effective treatments can be delivered. In this review we discuss the methods that are available for characterizing pluripotent stem cells and the techniques that have been applied in cells from companion animals. We describe characteristics which have been described consistently across reports as well as highlighting discrepant results. Significant steps have been made to define the in vitro culture requirements and drive lineage specific differentiation of pluripotent stem cells in companion animal species. However, additional basic research to compare pluripotent stem cell types and define characteristics of pluripotency in companion animal species is still required. V C 2017 International Society for Advancement of Cytometry

show abstract

“…For example, Doi et al found that, when using ESC‐derived neural cells, remaining undifferentiated ESCs induced tumor formation when grafted into monkey brains . A separate group found that, when progenitors of iPSCs reprogrammed with lentiviral vectors were transplanted into immunodeficient mice, more than 90% of the recipient animals formed invasive teratocarcinoma‐like tumors . Conversely, tumor‐free transplantation was achieved via the combination of transgene‐free reprogramming as well as the elimination of residual stem cells .…”

Section: Introductionmentioning

confidence: 99%

Concise Review: Molecular Cytogenetics and Quality Control: Clinical Guardians for Pluripotent Stem Cells

Rohani

Johnson

Naghsh

et al. 2018

Stem Cells Translational Medicine

View full text Add to dashboard Cite

Now that induced pluripotent stem cell (iPSC)‐based transplants have been performed in humans and organizations have begun producing clinical‐grade iPSCs, it is imperative that strict quality control standards are agreed upon. This is essential as both ESCs and iPSCs have been shown to accumulate genomic aberrations during long‐term culturing. These aberrations can include copy number variations, trisomy, amplifications of chromosomal regions, deletions of chromosomal regions, loss of heterozygosity, and epigenetic abnormalities. Moreover, although the differences between iPSCs and ESCs appear largely negligible when a high enough n number is used for comparison, the reprogramming process can generate further aberrations in iPSCs, including copy number variations and deletions in tumor‐suppressor genes. If mutations or epigenetic signatures are present in parental cells, these can also be carried over into iPSCs. To maximize patient safety, we recommend a set of standards to be utilized when preparing iPSCs for clinical use. Reprogramming methods that do not involve genomic integration should be used. Cultured cells should be grown using feeder‐free and serum‐free systems to avoid animal contamination. Karyotyping, whole‐genome sequencing, gene expression analyses, and standard sterility tests should all become routine quality control tests. Analysis of mitochondrial DNA integrity, whole‐epigenome analyses, as well as single‐cell genome sequencing of large cell populations may also prove beneficial. Furthermore, clinical‐grade stem cells need to be produced under accepted regulatory good manufacturing process standards. The creation of haplobanks that provide major histocompatibility complex matching is also recommended to improve allogeneic stem cell engraftment. Stem Cells Translational Medicine 2018;7:867–875

show abstract

Tumor-Free Transplantation of Patient-Derived Induced Pluripotent Stem Cell Progeny for Customized Islet Regeneration

Cited by 34 publications

References 50 publications

iPSC technology‐based regenerative therapy for diabetes

iPSC technology‐based regenerative therapy for diabetes

Characterization of companion animal pluripotent stem cells

Concise Review: Molecular Cytogenetics and Quality Control: Clinical Guardians for Pluripotent Stem Cells

Contact Info

Product

Resources

About