Generation of universal and hypoimmunogenic human pluripotent stem cells

Ye, Qingsong; Sung, Tzu Cheng; Yang, Jen Ming; Ling, Qing; He, Yan; Higuchi, Akon

doi:10.1111/cpr.12946

Cited by 27 publications

(17 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As an essential immune tolerance regulator in the human body, HLA-G5 is involved in processes such as foetal tolerance and autoimmunity during pregnancy, as well as inflammatory diseases and receiving allotransplantation from patients (37,38), and can achieve immune tolerance and protect the human body by interacting with inhibitory receptors on the surface of immune cells. HLA-G can interact with immunoglobulin-like proteins on dendritic cells (DC) (39,40), and through such self-made interactions, can suppress immune cells (41). Importantly, in normal tissues, HLA-G is most abundantly distributed on the surface of trophoblast cells in the placenta, which can effectively inhibit the local immune response in the uterus and promote the tolerance of the mother to the foetus (6,42).…”

Section: Discussionmentioning

confidence: 99%

Novel nucleic acid aptamer gold (Au)-nanoparticles (AuNPs-AptHLA-G5-1 and AuNPs-AptHLA-G5-2) to detect the soluble human leukocyte antigen G5 subtype (HLA-G5) in liquid samples

Wang

Yao

2021

Ann Transl Med

View full text Add to dashboard Cite

Background: The human leukocyte antigen G5 subtype (HLA-G5) is a major histocompatibility complex (MHC) molecule that is selectively expressed at the maternal-foetal tissue interface and is required for the successful implantation of the in vitro fertilized embryo. It is critical to detect HLA-G5, especially HLA-G5 expression in embryo fluid, during in vitro embryo incubation and culture. However, the specificity and sensitivity of traditional ELISA methods to detect sHLA-G5 are insufficient. This work aimed to explore novel nucleic acid aptamer gold (Au)-nanoparticles to detect soluble HLA-G5 in liquid samples.Methods: Soluble HLA-G5 was obtained using a prokaryotic expression system, and two novel aptamers (HLA-G5-Apt1 and HLA-G5-Apt2) detecting HLA-G5 were screened by the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) method. Small (10 nm) gold nanoparticles (AuNPs) were incubated with AptHLAs to form two novel nucleic acid aptamers: Au-nanoparticles (AuNPs-AptHLA-G5-1 and AuNPs-AptHLA-G5-2). Results:The results showed that AptHLA-G5-1 and AptHLA-G5-2 have a high affinity for HLA-G5 and can detect its presence in liquid samples. Using the colorimetric sensing method, AuNPs-AptHLA-G1 had a detection limit as low as 20 ng/mL (recovery range between 98.7% to 102.0%), while AuNPs-AptHLA-G2 had a detection limit as low as 20 ng/mL (recovery range between 98.9% to 103.6%).Conclusions: Our work demonstrates that novel AuNPs are efficient detectors for HLA-G5 and are useful for diagnosis and treatment in the field of obstetrics-gynaecology.

show abstract

Section: Discussionmentioning

confidence: 99%

Novel nucleic acid aptamer gold (Au)-nanoparticles (AuNPs-AptHLA-G5-1 and AuNPs-AptHLA-G5-2) to detect the soluble human leukocyte antigen G5 subtype (HLA-G5) in liquid samples

Wang

Yao

2021

Ann Transl Med

View full text Add to dashboard Cite

show abstract

“…Recently, several engineering strategies to reduce immune rejection have emerged by modification of HLA molecules. [7][8][9] Disruption of all HLA-I (classical HLA-A, HLA-B, HLA-C and non-classical HLA-E, HLA-F, HLA-G) and HLA-II (HLA-DR, HLA-DQ, HLA-DP) by knocking out B2M and CIITA genes [10][11][12] results in reduced immune surveillance 13 and NK cell-mediated killing because of a lack of ligands for the inhibitory receptors of NK cells. 12,14 To overcome these barriers, overexpression of HLA-I (e.g., HLA-E, 15 HLA-G, 16,17 and HLA-A 18 ) or CD47 19 on the surface of hPSCs lacking HLA-I and HLA-II may be a significant attempt.…”

Section: Allogeneic Immune Rejection Is Caused Mainly By Mismatches Ofmentioning

confidence: 99%

“…Allogeneic immune rejection is caused mainly by mismatches of HLAs between the donor and recipient. Recently, several engineering strategies to reduce immune rejection have emerged by modification of HLA molecules 7–9 . Disruption of all HLA‐I (classical HLA‐A, HLA‐B, HLA‐C and non‐classical HLA‐E, HLA‐F, HLA‐G) and HLA‐II (HLA‐DR, HLA‐DQ, HLA‐DP) by knocking out B2M and CIITA genes 10–12 results in reduced immune surveillance 13 and NK cell‐mediated killing because of a lack of ligands for the inhibitory receptors of NK cells 12,14 .…”

Section: Introductionmentioning

confidence: 99%

Genome editing HLA alleles for a pilot immunocompatible hESC line in a Chinese hESC bank for cell therapies

Ji,

Niu,

Fang

et al. 2023

Cell Proliferation

View full text Add to dashboard Cite

Robust allogeneic immune reactions after transplantation impede the translational pace of human embryonic stem cells (hESCs)-based therapies. Selective genetic editing of human leucocyte antigen (HLA) molecules has been proposed to generate hESCs with immunocompatibility, which, however, has not been specifically designed for the Chinese population yet. Herein, we explored the possibility of customizing immunocompatible hESCs based on Chinese HLA typing characteristics. We generated an immunocompatible hESC line by disrupting HLA-B, HLA-C, and CIITA genes while retaining HLA-A*11:01 (HLA-A*11:01-retained, HLA-A11 R ), which covers $21% of the Chinese population. The immunocompatibility of HLA-A11 R hESCs was verified by in vitro co-culture and confirmed in humanized mice with established human immunity. Moreover, we precisely knocked an inducible caspase-9 suicide cassette into HLA-A11 R hESCs (iC9-HLA-A11 R ) to promote safety. Compared with wide-type hESCs, HLA-A11 R hESC-derived endothelial cells elicited much weaker immune responses to human HLA-A11 + T cells, while maintaining HLA-I moleculemediated inhibitory signals to natural killer (NK) cells. Additionally, iC9-HLA-A11 R hESCs could be induced to undergo apoptosis efficiently by AP1903. Both cell lines displayed genomic integrity and low risks of off-target effects. In conclusion, we

show abstract

“…Moreover, observing the current progress in the development of medicine and sciences in the field of biotechnology, tissue engineering, and cellular transformation, the transformation of stem cells taken from the patient and their differentiation into insulin and glucagon producing cells seems a reasonable and very promising approach. Additionally, stem cells with ablation of HLA complex gain more and more interest as they give the possibility to construct universal cell lines which, can be applied for any patient without the need for immunosuppression [ 40 ].…”

Section: Available Treatments For Patients With Type 1 Diabetesmentioning

confidence: 99%

Stem Cells as a Source of Pancreatic Cells for Production of 3D Bioprinted Bionic Pancreas in the Treatment of Type 1 Diabetes

Wszoła¹,

Nitarska²,

Cywoniuk³

et al. 2021

Cells

View full text Add to dashboard Cite

Type 1 diabetes (T1D) is the third most common autoimmune disease which develops due to genetic and environmental risk factors. Often, intensive insulin therapy is insufficient, and patients require a pancreas or pancreatic islets transplant. However, both solutions are associated with many possible complications, including graft rejection. The best approach seems to be a donor-independent T1D treatment strategy based on human stem cells cultured in vitro and differentiated into insulin and glucagon-producing cells (β and α cells, respectively). Both types of cells can then be incorporated into the bio-ink used for 3D printing of the bionic pancreas, which can be transplanted into T1D patients to restore glucose homeostasis. The aim of this review is to summarize current knowledge about stem cells sources and their transformation into key pancreatic cells. Last, but not least, we comment on possible solutions of post-transplant immune response triggered stem cell-derived pancreatic cells and their potential control mechanisms.

show abstract

Generation of universal and hypoimmunogenic human pluripotent stem cells

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 27 publications

References 54 publications

Novel nucleic acid aptamer gold (Au)-nanoparticles (AuNPs-AptHLA-G5-1 and AuNPs-AptHLA-G5-2) to detect the soluble human leukocyte antigen G5 subtype (HLA-G5) in liquid samples

Novel nucleic acid aptamer gold (Au)-nanoparticles (AuNPs-AptHLA-G5-1 and AuNPs-AptHLA-G5-2) to detect the soluble human leukocyte antigen G5 subtype (HLA-G5) in liquid samples

Genome editing HLA alleles for a pilot immunocompatible hESC line in a Chinese hESC bank for cell therapies

Stem Cells as a Source of Pancreatic Cells for Production of 3D Bioprinted Bionic Pancreas in the Treatment of Type 1 Diabetes

Contact Info

Product

Resources

About