International Journal of Molecular Sciences

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13 pages, 2961 KiB

Open AccessArticle

IGF-1 Genome-Edited Human MSCs Exhibit Robust Anti-Arthritogenicity in Collagen-Induced Arthritis

by Dong-Sik Chae, Seongho Han and Sung-Whan Kim

Int. J. Mol. Sci. 2024, 25(8), 4442; https://doi.org/10.3390/ijms25084442 - 18 Apr 2024

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Abstract

Stem cell therapy stands out as a promising avenue for addressing arthritis treatment. However, its therapeutic efficacy requires further enhancement. In this study, we investigated the anti-arthritogenic potential of human amniotic mesenchymal stem cells (AMM) overexpressing insulin-like growth factor 1 (IGF-1) in a [...] Read more.

Stem cell therapy stands out as a promising avenue for addressing arthritis treatment. However, its therapeutic efficacy requires further enhancement. In this study, we investigated the anti-arthritogenic potential of human amniotic mesenchymal stem cells (AMM) overexpressing insulin-like growth factor 1 (IGF-1) in a collagen-induced mouse model. The IGF-1 gene was introduced into the genome of AMM through transcription activator-like effector nucleases (TALENs). We assessed the in vitro immunomodulatory properties and in vivo anti-arthritogenic effects of IGF-1-overexpressing AMM (AMM/I). Co-culture of AMM/I with interleukin (IL)-1β-treated synovial fibroblasts significantly suppressed NF-kB levels. Transplantation of AMM/I into mice with collagen-induced arthritis (CIA) led to significant attenuation of CIA progression. Furthermore, AMM/I administration resulted in the expansion of regulatory T-cell populations and suppression of T-helper-17 cell activation in CIA mice. In addition, AMM/I transplantation led to an increase in proteoglycan expression within cartilage and reduced infiltration by inflammatory cells and also levels of pro-inflammatory factors including cyclooxygenase-2 (COX-2), IL-1β, NF-kB, and tumor necrosis factor (TNF)-α. In conclusion, our findings suggest that IGF-1 gene-edited human AMM represent a novel alternative therapeutic strategy for the treatment of arthritis. Full article

(This article belongs to the Special Issue Recent Advancements in Genome Editing Technologies and Their Applications for Human Diseases)

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18 pages, 816 KiB

Open AccessArticle

Polymorphic Variants of Genes Encoding Angiogenesis-Related Factors in Infertile Women with Recurrent Implantation Failure

by Aleksandra E. Mrozikiewicz, Grażyna Kurzawińska, Marcin Ożarowski, Michał Walczak, Katarzyna Ożegowska and Piotr Jędrzejczak

Int. J. Mol. Sci. 2023, 24(5), 4267; https://doi.org/10.3390/ijms24054267 - 21 Feb 2023

Cited by 2 | Viewed by 1762

Abstract

Recurrent implantation failure (RIF) is a global health issue affecting a significant number of infertile women who undergo in vitro fertilization (IVF) cycles. Extensive vasculogenesis and angiogenesis occur in both maternal and fetal placental tissues, and vascular endothelial growth factor (VEGF) and fibroblast [...] Read more.

Recurrent implantation failure (RIF) is a global health issue affecting a significant number of infertile women who undergo in vitro fertilization (IVF) cycles. Extensive vasculogenesis and angiogenesis occur in both maternal and fetal placental tissues, and vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) family molecules and their receptors are potent angiogenic mediators in the placenta. Five single nucleotide polymorphisms (SNPs) in the genes encoding angiogenesis-related factors were selected and genotyped in 247 women who had undergone the ART procedure and 120 healthy controls. Genotyping was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). A variant of the kinase insertion domain receptor (KDR) gene (rs2071559) was associated with an increased risk of infertility after adjusting for age and BMI (OR = 0.64; 95% CI: 0.45–0.91, p = 0.013 in a log-additive model). Vascular endothelial growth factor A (VEGFA) rs699947 was associated with an increased risk of recurrent implantation failures under a dominant (OR = 2.34; 95% CI: 1.11–4.94, p_adj. = 0.022) and a log-additive model (OR = 0.65; 95% CI 0.43–0.99, p_adj. = 0.038). Variants of the KDR gene (rs1870377, rs2071559) in the whole group were in linkage equilibrium (D’ = 0.25, r² = 0.025). Gene–gene interaction analysis showed the strongest interactions between the KDR gene SNPs rs2071559–rs1870377 (p = 0.004) and KDR rs1870377–VEGFA rs699947 (p = 0.030). Our study revealed that the KDR gene rs2071559 variant may be associated with infertility and rs699947 VEGFA with an increased risk of recurrent implantation failures in infertile ART treated Polish women. Full article

(This article belongs to the Special Issue Recent Advancements in Genome Editing Technologies and Their Applications for Human Diseases)

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Review

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25 pages, 1330 KiB

Open AccessReview

Applications of Genome Editing Technologies in CAD Research and Therapy with a Focus on Atherosclerosis

by Michelle C. E. Mak, Rijan Gurung and Roger S. Y. Foo

Int. J. Mol. Sci. 2023, 24(18), 14057; https://doi.org/10.3390/ijms241814057 - 13 Sep 2023

Cited by 1 | Viewed by 1573

Abstract

Cardiovascular diseases, particularly coronary artery disease (CAD), remain the leading cause of death worldwide in recent years, with myocardial infarction (MI) being the most common form of CAD. Atherosclerosis has been highlighted as one of the drivers of CAD, and much research has [...] Read more.

Cardiovascular diseases, particularly coronary artery disease (CAD), remain the leading cause of death worldwide in recent years, with myocardial infarction (MI) being the most common form of CAD. Atherosclerosis has been highlighted as one of the drivers of CAD, and much research has been carried out to understand and treat this disease. However, there remains much to be better understood and developed in treating this disease. Genome editing technologies have been widely used to establish models of disease as well as to treat various genetic disorders at their root. In this review, we aim to highlight the various ways genome editing technologies can be applied to establish models of atherosclerosis, as well as their therapeutic roles in both atherosclerosis and the clinical implications of CAD. Full article

(This article belongs to the Special Issue Recent Advancements in Genome Editing Technologies and Their Applications for Human Diseases)

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