Combinatorial islet protective therapeutic approaches in β‐cell transplantation: Rationally designed solutions using a target product profile DOI Creative Commons
Katie Lu, Timothy Brauns, Ann E. Sluder

et al.

FASEB BioAdvances, Journal Year: 2023, Volume and Issue: 5(7), P. 287 - 304

Published: June 2, 2023

Abstract While progress has been made in the development of islet cell transplantation (ICT) as a viable alternative to use exogenous insulin therapy treatment type 1 diabetes, it not yet achieved its full potential clinical studies. Ideally, ICT would enable lifelong maintenance euglycemia without need for insulin, blood glucose monitoring or systemic immune suppression. To achieve such an optimal result, therapeutic approaches should simultaneously promote long‐term viability, functionality, and localized protection. In practice, however, these factors are typically tackled individually. Furthermore, while requirements implicitly acknowledged across numerous publications, literature contains few comprehensive articulations target product profile (TPP) product, including key characteristics safety efficacy. This review aims provide novel TPP presents promising tried untried combinatorial that could be used profile. We also highlight regulatory barriers adoption ICT, particularly United States, where is only approved academic trials reimbursed by insurance carriers. Overall, this argues clear definition addition help overcome widespread diabetes.

Language: Английский

Harnessing cellular therapeutics for type 1 diabetes mellitus: progress, challenges, and the road ahead DOI
Alessandro Grattoni, Gregory S. Korbutt, Alice A. Tomei

et al.

Nature Reviews Endocrinology, Journal Year: 2024, Volume and Issue: 21(1), P. 14 - 30

Published: Sept. 3, 2024

Language: Английский

Citations

17
Immune-privileged tissues formed from immunologically cloaked mouse embryonic stem cells survive long term in allogeneic hosts DOI Creative Commons

Jeffrey Harding,

Kristina Vintersten-Nagy,

Huijuan Yang

et al.

Nature Biomedical Engineering, Journal Year: 2023, Volume and Issue: 8(4), P. 427 - 442

Published: Nov. 23, 2023

Abstract The immunogenicity of transplanted allogeneic cells and tissues is a major hurdle to the advancement cell therapies. Here we show that overexpression eight immunomodulatory transgenes ( Pdl1 , Cd200 Cd47 H2-M3 Fasl Serpinb9 Ccl21 Mfge8 ) in mouse embryonic stem (mESCs) sufficient immunologically ‘cloak’ as well derived from them, allowing their survival for months outbred inbred recipients. Overexpression human orthologues these genes ESCs abolished activation peripheral blood mononuclear inflammatory responses. Moreover, by using previously reported FailSafe transgene system, which transcriptionally links gene essential division with an inducible cell-proliferation-dependent kill switch, generated cloaked mESCs served immune-privileged subcutaneous sites protected uncloaked xenogeneic rejection immune-competent hosts. combination cloaking technologies may allow generation safe allogeneically accepted lines off-the-shelf products.

Language: Английский

Citations

26
Recent Advances in Alginate-Based Hydrogels for Cell Transplantation Applications DOI Creative Commons

Alireza Kavand,

François Noverraz,

Sandrine Gerber‐Lemaire

et al.

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(4), P. 469 - 469

Published: March 27, 2024

With its exceptional biocompatibility, alginate emerged as a highly promising biomaterial for large range of applications in regenerative medicine. Whether the form microparticles, injectable hydrogels, rigid scaffolds, or bioinks, provides versatile platform encapsulating cells and fostering an optimal environment to enhance cell viability. This review aims highlight recent studies utilizing diverse formulations transplantation, offering insights into efficacy treating various diseases injuries within field

Language: Английский

Citations

9
Immune Evasion in Stem Cell-Based Diabetes Therapy—Current Strategies and Their Application in Clinical Trials DOI Creative Commons
Razik Mu-u-min, Abdoulaye Diané,

Asma Allouch

et al.

Biomedicines, Journal Year: 2025, Volume and Issue: 13(2), P. 383 - 383

Published: Feb. 6, 2025

Background/Objectives: Human pancreatic islet transplantation shows promise for long-term glycemic control in diabetes patients. A shortage of healthy donors and the need continuous immunosuppressive therapy complicates this. Enhancing our understanding immune tolerance mechanisms related to graft rejection is crucial generate safer strategies. This review will examine advancements protection strategies stem cell-derived discuss key clinical trials involving β-cells their protective against host system. Methods: comprehensive literature search was performed on peer-reviewed publications Google Scholar, Pubmed, Scopus up September 2024 extract relevant studies various evasion humans. The extended assimilate all wherein are transplanted treat diabetes. Results: Our analysis highlighted importance human pluripotent cells (hPSCs) as a potentially unlimited source insulin-producing β-cells. These can be an effective insulin patients if they protected Various protection, such encapsulation genetic manipulation, currently being studied clinically tested. Conclusions: Investigating hPSC-derived islets may help achieve cure without relying exogenous insulin. Although reports show reducing dependency patients, safety efficacy needs further promote use solution

Language: Английский

Citations

1
No Time to Die—How Islets Meet Their Demise in Transplantation DOI Creative Commons
Atharva Kale, Natasha M. Rogers

Cells, Journal Year: 2023, Volume and Issue: 12(5), P. 796 - 796

Published: March 3, 2023

Islet transplantation represents an effective treatment for patients with type 1 diabetes mellitus (T1DM) and severe hypoglycaemia unawareness, capable of circumventing impaired counterregulatory pathways that no longer provide protection against low blood glucose levels. The additional beneficial effect normalizing metabolic glycaemic control is the minimisation further complications related to T1DM insulin administration. However, require allogeneic islets from up three donors, long-term independence inferior achieved solid organ (whole pancreas) transplantation. This likely due fragility caused by isolation process, innate immune responses following portal infusion, auto- allo-immune-mediated destruction β-cell exhaustion review covers specific challenges islet vulnerability dysfunction affect cell survival

Language: Английский

Citations

21
Emerging strategies to bypass transplant rejection via biomaterial-assisted immunoengineering: Insights from islets and beyond DOI Creative Commons
Samin Abbaszadeh,

Vahideh Nosrati‐Siahmazgi,

Kiyan Musaie

et al.

Advanced Drug Delivery Reviews, Journal Year: 2023, Volume and Issue: 200, P. 115050 - 115050

Published: Aug. 6, 2023

Novel transplantation techniques are currently under development to preserve the function of impaired tissues or organs. While current technologies can enhance survival recipients, they have remained elusive date due graft rejection by undesired in vivo immune responses despite systemic prescription immunosuppressants. The need for life-long immunomodulation and serious adverse effects medicines, novel biomaterial-based immunoengineering strategies has attracted much attention lately. Immunomodulatory 3D platforms alter locally and/or prevent transplant through protection from attack system. These new approaches aim overcome complexity long-term administration immunosuppressants, including risks infection, cancer incidence, toxicity. In addition, decrease effective dose delivered drugs via direct delivery at site. this review, we comprehensively address mechanisms, followed recent developments prolong survival. We also compare efficacy safety these with conventional agents. Finally, challenges barriers clinical translation transplants prospects discussed.

Language: Английский

Citations

17
Immunoprotection Strategies in β‐Cell Replacement Therapy: A Closer Look at Porcine Islet Xenotransplantation DOI Creative Commons

Sarah Grimus,

Victoria Sarangova,

Petra B. Welzel

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(31)

Published: June 17, 2024

Abstract Type 1 diabetes mellitus (T1DM) is characterized by absolute insulin deficiency primarily due to autoimmune destruction of pancreatic β‐cells. The prevailing treatment for T1DM involves daily subcutaneous injections, but a substantial proportion patients face challenges such as severe hypoglycemic episodes and poorly controlled hyperglycemia. For patients, more effective therapeutic option the replacement β‐cells through allogeneic transplantation either entire pancreas or isolated islets. Unfortunately, scarcity transplantable human organs has led growing list waiting an islet transplant. One potential alternative xenotransplantation porcine However, inter‐species molecular incompatibilities, tissues trigger robust immune response in humans, leading xenograft rejection. Several promising strategies aim overcome this challenge enhance long‐term survival functionality xenogeneic grafts. These include use islets derived from genetically modified pigs, immunoisolation encapsulation biocompatible materials, creation immunomodulatory microenvironment co‐transplanting with accessory cells utilizing biomaterials. This review concentrates on delineating primary obstacles elucidates fundamental principles recent breakthroughs aimed at addressing these challenges.

Language: Английский

Citations

7
The Current Status of Allogenic Islet Cell Transplantation DOI Creative Commons
Zofia Czarnecka, Nidheesh Dadheech, Haide Razavy

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(20), P. 2423 - 2423

Published: Oct. 10, 2023

Type 1 Diabetes (T1D) is an autoimmune destruction of pancreatic beta cells. The development the Edmonton Protocol for islet transplantation in 2000 revolutionized T1D treatment and offered a glimpse at cure disease. In 2022, 20-year follow-up findings cell demonstrated long-term safety despite chronic immunosuppression. Protocol, however, remains limited by two obstacles: scarce organ donor availability risks associated with To overcome these challenges, search has begun alternative source. 2006, pluripotency genomic factors, coined “Yamanaka Factors,” were discovered, which reprogram mature somatic cells back to their embryonic, pluripotent form (iPSC). iPSCs can then be differentiated into specialized types, including This discovery opened gateway personalized medicine approach treating diabetes, circumventing issues supply this review, we present brief history allogenic from early days remnant work on encapsulating stem cell-derived We review data outcomes ongoing challenges transplant.

Language: Английский

Citations

15
Antigen-specific immunotherapies in type 1 diabetes DOI
Xuejiao Zhang,

Ying Dong,

Dianyuan Liu

et al.

Journal of Trace Elements in Medicine and Biology, Journal Year: 2022, Volume and Issue: 73, P. 127040 - 127040

Published: July 15, 2022

Language: Английский

Citations

22
Advances in Organ and Tissue Xenotransplantation DOI

Asghar Ali,

Elisabeth Kemter, Eckhard Wolf

et al.

Annual Review of Animal Biosciences, Journal Year: 2023, Volume and Issue: 12(1), P. 369 - 390

Published: Oct. 31, 2023

End-stage organ failure can result from various preexisting conditions and occurs in patients of all ages, transplantation remains its only treatment. In recent years, extensive research has been done to explore the possibility transplanting animal organs into humans, a process referred as xenotransplantation. Due their matching sizes other anatomical physiological similarities with pigs are preferred donor species. Organ rejection due host immune response possible interspecies infectious pathogen transmission have biggest hurdles xenotransplantation's success. Use genetically engineered tissue donors for xenotransplantation helped address these hurdles. Although several preclinical trials conducted nonhuman primates, some barriers still exist demand further efforts. This review focuses on advances remaining challenges

Language: Английский

Citations

12