A Future for Autologous Hematopoietic Stem Cell Transplantation in Type 1 Diabetes

Megen, Kayleigh M. van; Wout, Ernst-Jan T van 't; Forman, Stephen J.; Roep, Bart O.

doi:10.3389/fimmu.2018.00690

Cited by 13 publications

(12 citation statements)

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“…Stem cell transplantation is actively studied as a therapeutic option for autoimmune and degenerative disorders (e.g., HSCs for type 1 diabetes and NSCs for Alzheimer's disease) (19,171). However, their application is challenging, as in vitro, the mutation accumulation rate in adult stem cells is nearly 40-fold higher than in vivo, which is likely caused by oxidative stress imposed by culturing conditions (90,144).…”

Section: Resultsmentioning

confidence: 99%

Metabolic Regulation of Stem Cells and Differentiation: A Forkhead Box O Transcription Factor Perspective

Ludikhuize

Colman

2021

Antioxidants & Redox Signaling

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Significance: Stem cell activation and differentiation occur along changes in cellular metabolism. Metabolic transitions translate into changes in redox balance, cell signaling, and epigenetics, thereby regulating these processes. Metabolic transitions are key regulators of cell fate and exemplify the moonlighting nature of many metabolic enzymes and their associated metabolites. Recent Advances: Forkhead box O transcription factors (FOXOs) are bona fide regulators of cellular homeostasis. FOXOs are multitasking proteins able to regulate cell cycle, cellular metabolism, and redox state. Recent and ongoing research poses FOXOs as key factors in stem cell maintenance and differentiation in several tissues. Critical Issues: The multitasking nature of FOXOs and their tissue-specific expression patterns hinders to disclose a possible conserved mechanism of regulation of stem cell maintenance and differentiation. Moreover, cellular metabolism, cell signaling, and epigenetics establish complex regulatory interactions, which challenge the establishment of the causal/temporal nature of metabolic changes and stem cell activation and differentiation. Future Directions: The development of single-cell technologies and in vitro models able to reproduce the dynamics of stem cell differentiation are actively contributing to define the role of metabolism in this process. This knowledge is key to understanding and designing therapies for those pathologies where the balance between proliferation and differentiation is lost. Importantly, metabolic interventions could be applied to optimize stem cell cultures meant for therapeutical applications, such as transplantations, to treat autoimmune and degenerative disorders. Antioxid. Redox Signal. 00, 000-000.

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Section: Resultsmentioning

confidence: 99%

Metabolic Regulation of Stem Cells and Differentiation: A Forkhead Box O Transcription Factor Perspective

Ludikhuize

Colman

2021

Antioxidants & Redox Signaling

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“…The putative mechanism points to greater diversity in the T-cell repertoire ( 11 ), thymus reactivation of regulatory T cells (Tregs) ( 12 ), and an increase in the function or number of Tregs ( 13 ). The clinical efficacy of aHSCT among patients with type 1 diabetes was remarkable, with most achieving long-term insulin independence ( 13 , 14 ). Our patient, who had no history of autoimmunity but carried high-risk HLA-DR4 and had prediabetes, underwent aHSCT before pembrolizumab therapy.…”

Section: Discussionmentioning

confidence: 99%

Anti–PD-1 Therapy–Associated Type 1 Diabetes in a Pediatric Patient With Relapsed Classical Hodgkin Lymphoma

et al. 2020

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Immune checkpoint inhibitors (ICIs) perturb T-cell regulatory pathways to enhance antitumor immunity. However, an increase reporting of ICI-associated diabetes is observed in adults. To our knowledge, no cases have been reported in the pediatric population. RESEARCH DESIGN AND METHODS We describe a pediatric case of ICI-associated type 1 diabetes in a 12-year-old Hispanic boy with Hodgkin lymphoma. The patient had a history of autologous hematopoietic stem cell transplantation and was treated with pembrolizumab after disease progression. RESULTS The patient was admitted for diabetic ketoacidosis after five cycles of pembrolizumab. The patient was discharged with daily insulin injections and has continued on exogenous insulin ever since. CONCLUSIONS The expanded ICI use may lead to more cases in pediatric patients as has been observed in adults. Considering the acute manifestation of diabetes and the added burden of lifelong insulin therapy, in particular for pediatric patients and their families, monitoring and education of ICI-associated diabetes in children is needed. Insulin-dependent diabetes associated with immune checkpoint inhibitors (ICIs) is a rare phenomenon but of high clinical significance due to its presentation as potentially life-threatening diabetic ketoacidosis (DKA). In the setting of advanced malignancies, ICI-associated diabetes may seem peripheral, but its chronicity, complications, and daily glucose monitoring and insulin injections drastically alter patients' quality of life and complicate cancer treatment. Moreover, the unprecedented level of interest in immunotherapy research will lead to more widespread use of ICIs and a subsequent increase in diabetes, as evidenced by recent data (1-3). One study reported 283 new cases during a 4-year period, with more than half reported in 2017 (1). The primary cancer types were melanoma (43%), lung (32%), and renal (10%), indicative of early ICI approvals in these tumors. While the nature of ICI-associated diabetes is better defined for melanoma, other malignancies, such as lymphoma, are rarely reported, making it difficult to assess patient characteristics in various types of cancer that are approved for ICI use, especially for hematologic malignancies.

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“…In recent years, autologous HSCT has been used in clinical trials to eliminate various types of refractory autoimmune diseases such as multiple sclerosis, systemic sclerosis (SSc), systemic lupus erythematous (SLE), rheumatoid arthritis (RA), Crohn's disease, juvenile arthritis, and type 1 diabetes (T1D), presenting better results than traditional therapies and showing promising prospects for long-term remission of autoimmune diseases without IS ( 90 , 93 , 95 , 101 – 105 ). At present, autologous HSCT has also been widely used in various types of liver cirrhosis, improving liver function in varying degrees ( 106 – 109 ).…”

Section: Hematopoietic Stem Cell Transplantation (Hsct) For the Inducmentioning

confidence: 99%

Progress in Liver Transplant Tolerance and Tolerance-Inducing Cellular Therapies

Chang

Guo

et al. 2020

Front. Immunol.

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Liver transplantation is currently the most effective method for treating end-stage liver disease. However, recipients still need long-term immunosuppressive drug treatment to control allogeneic immune rejection, which may cause various complications and affect the long-term survival of the recipient. Many liver transplant researchers constantly pursue the induction of immune tolerance in liver transplant recipients, immunosuppression withdrawal, and the maintenance of good and stable graft function. Although allogeneic liver transplantation is more tolerated than transplantation of other solid organs, and it shows a certain incidence of spontaneous tolerance, there is still great risk for general recipients. With the gradual progress in our understanding of immune regulatory mechanisms, a variety of immune regulatory cells have been discovered, and good results have been obtained in rodent and non-human primate transplant models. As immune cell therapies can induce long-term stable tolerance, they provide a good prospect for the induction of tolerance in clinical liver transplantation. At present, many transplant centers have carried out tolerance-inducing clinical trials in liver transplant recipients, and some have achieved gratifying results. This article will review the current status of liver transplant tolerance and the research progress of different cellular immunotherapies to induce this tolerance, which can provide more support for future clinical applications.

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A Future for Autologous Hematopoietic Stem Cell Transplantation in Type 1 Diabetes

Cited by 13 publications

References 50 publications

Metabolic Regulation of Stem Cells and Differentiation: A Forkhead Box O Transcription Factor Perspective

Metabolic Regulation of Stem Cells and Differentiation: A Forkhead Box O Transcription Factor Perspective

Anti–PD-1 Therapy–Associated Type 1 Diabetes in a Pediatric Patient With Relapsed Classical Hodgkin Lymphoma

Progress in Liver Transplant Tolerance and Tolerance-Inducing Cellular Therapies

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