In vitro assessment of cord blood–derived proinsulin-specific regulatory T cells for cellular therapy in type 1 diabetes

Paul, Mahinder; Dayal, Devi; Bhansali, Anil; Dhaliwal, Lakhbir Kaur; Sachdeva, Naresh

doi:10.1016/j.jcyt.2018.09.004

Cited by 10 publications

(3 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hence, polyclonal CB Tregs might provide a more comprehensive repertoire from which to seed the periphery. Indeed, a recent study has demonstrated the capacity to expand proinsulin (PI)-reactive Tregs from CB with increased yield compared to peripheral blood from subjects with T1D (137). The resultant pool of PI-specific Tregs was found to maintain lineage stability and suppressive function.…”

Section: Discussionmentioning

confidence: 99%

Human Regulatory T Cells From Umbilical Cord Blood Display Increased Repertoire Diversity and Lineage Stability Relative to Adult Peripheral Blood

et al. 2020

View full text Add to dashboard Cite

Tregs. Interestingly, expression of canonical Treg markers, such as FOXP3, TIGIT, and IKZF2, were increased in CB CD4 + CD127 + conventional T cells (Tconv) compared to APB Tconv, post-expansion, implying perinatal T cells may adopt a default regulatory program. Collectively, these data identify surface markers (namely CXCR3) that could be depleted to improve purity and stability of APB Tregs, and support the use of expanded CB Tregs as a potentially optimal ACT modality for the treatment of autoimmune and inflammatory diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

Human Regulatory T Cells From Umbilical Cord Blood Display Increased Repertoire Diversity and Lineage Stability Relative to Adult Peripheral Blood

et al. 2020

View full text Add to dashboard Cite

show abstract

“…These obstacles inspired the design of strategies to target T cell receptors (TCRs) and chimeric antigen receptors (CARs) to engineer antigen-specific Tregs [ 42 ]. Of note, UCB can serve as an excellent source for producing functional antigen-specific Tregs for immunotherapy [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Multiply restimulated human cord blood-derived Tregs maintain stabilized phenotype and suppressive function and predict their therapeutic effects on autoimmune diabetes

Bi,

Kong,

Peng

et al. 2024

Diabetol Metab Syndr

View full text Add to dashboard Cite

Background Regulatory T cells (Tregs) are involved in the maintenance of immune homeostasis and immune regulation. Clinical trials on the adoptive transfer of Tregs have been ongoing for > 10 years. However, many unresolved issues remain in the production of readymade Treg products and selection of patients. Hence, this study aimed to develop a method to expand off-the-shelf Tregs derived from umbilical cord blood (UCB-Tregs) in vitro without changing their phenotype and inhibitory function. In addition, the study intended to design an approach to precisely select patients who are more likely to benefit from the adoptive Treg transfer therapy. Methods UCB-Tregs were isolated and cultured in a medium containing human recombinant IL-2 and rapamycin and then multiply restimulated with human T-activator CD3/CD28 dynabeads. The phenotype and suppressive capacity of Tregs were assessed on days 18 and 42. The relationship between the suppressive function of UCB-Tregs in vitro and clinical indicators was analyzed, and the ability of the in vitro suppressive capacity to predict the in vivo therapeutic effects was evaluated. Results UCB-Tregs expanded 123-fold and 5,981-fold at 18 and 42 days, respectively. The suppressive function of UCB-Tregs on the proliferation of immune cells at 42 days was not significantly different compared with that of UCB-Tregs obtained at 18 days. The suppression rate of UCB-Tregs to PBMCs was negatively correlated with the course of diabetes. Moreover, the high-suppression group exhibited a better treatment response than the low-suppression group during the 12-month follow-up period. Conclusions Multiply restimulated UCB-Tregs expanded at a large scale without any alterations in their classical phenotypic features and inhibitory functions. The suppressive function of Tregs in vitro was negatively correlated with the disease duration. The present study revealed the possibility of predicting the in vivo therapeutic effects via the in vitro inhibition assay. Thus, these findings provided a method to obtain off-the-shelf Treg products and facilitated the selection of patients who are likely to respond to the treatment, thereby moving toward the goal of precision treatment.

show abstract

“…In particular, India which is currently placed 17 th in the global T1D research ranking is likely to improve its ranking due to a sustained focus on pediatric T1D research during the past decade [15]. Several groups of researchers who are engaged in pediatric T1D research in India over the past two decades will likely contribute to an improved publication output [16][17][18][19][20][21].…”

Section: Medium Of Research Communicationmentioning

confidence: 99%

Pediatric type 1 diabetes research in the 21st century: a scientometric review

Gupta

Dayal²

2020

pedm

Self Cite

View full text Add to dashboard Cite

Introduction: Scientometric studies help scientists to identify research gaps and plan future research. There is no scientometric assessment of research on childhood onset type 1 diabetes (T1D), despite an intensive research in this field over the past 2 decades. Aim of the study: To provide a scientometric assessment of global research output in pediatric T1D. Material and methods: Publications on pediatric T1D indexed in Scopus database over the 20-year period from 2000 to 2019 were examined. The most productive and impactful countries, organizations and authors, trends in research, the media of publications and characteristics of high cited publications were identified using appropriate bibliographic tools. Results: Pediatric T1D research registered 7.84% and 79.99% annual and 10-year cumulative growth and averaged 19.35 citations per paper (CPP). The field witnessed an uneven participation of 141 countries, wherein 82.67% of the global research output share came from top 10 countries. USA leads the ranking with 29.76% share, followed by UK (10.56%), Germany, Italy, Sweden and Australia (5.15% to 7.88%), and Poland, Finland, Canada and Denmark (3.04% to 4.24%). Five countries which registered relative citation index (RCI) higher than their group average of 1.63 were Finland (2.30), UK (1.82), Canada (1.77), Denmark and USA (1.74 each). The number of participating organizations and authors was 3627 and 5596 respectively. Conclusions: The USA and Finland are the most productive and the most impactful countries respectively in global pediatric T1D research. The contribution from developing countries especially from Southeast Asia is meager despite a large disease burden.

show abstract

In vitro assessment of cord blood–derived proinsulin-specific regulatory T cells for cellular therapy in type 1 diabetes

Cited by 10 publications

References 48 publications

Human Regulatory T Cells From Umbilical Cord Blood Display Increased Repertoire Diversity and Lineage Stability Relative to Adult Peripheral Blood

Human Regulatory T Cells From Umbilical Cord Blood Display Increased Repertoire Diversity and Lineage Stability Relative to Adult Peripheral Blood

Multiply restimulated human cord blood-derived Tregs maintain stabilized phenotype and suppressive function and predict their therapeutic effects on autoimmune diabetes

Pediatric type 1 diabetes research in the 21st century: a scientometric review

Contact Info

Product

Resources

About