ILK regulates MSCs survival and angiogenesis partially through AKT and mTOR signaling pathways

Zeng, Bin; Liu, Lei; Wang, Shaofeng; Dai, Zhiguo

doi:10.1016/j.acthis.2017.04.003

Cited by 20 publications

(8 citation statements)

References 26 publications

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“…Integrin-linked kinase (ILK) overexpression in MSCs increased their survival and angiogenesis via AKT and mTOR signaling pathways in an infarcted myocardium. It was noticed that the ILKoverexpressed MSCs increased MSCs survival at day 4, and angiogenesis at week 3 post transplantation [47].…”

Section: Improving Survivalmentioning

confidence: 99%

Improved therapeutics of modified mesenchymal stem cells: an update

Pei²,

et al. 2020

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Background: Mesenchymal stromal cells (MSCs) have attracted intense interest due to their powerful intrinsic properties of self-regeneration, immunomodulation and multi-potency, as well as being readily available and easy to isolate and culture. Notwithstanding, MSC based therapy suffers reduced efficacy due to several challenges which include unfavorable microenvironmental factors in vitro and in vivo. Body: In the quest to circumvent these challenges, several modification techniques have been applied to the naïve MSC to improve its inherent therapeutic properties. These modification approaches can be broadly divided into two groups to include genetic modification and preconditioning modification (using drugs, growth factors and other molecules). This field has witnessed great progress and continues to gather interest and novelty. We review these innovative approaches in not only maintaining, but also enhancing the inherent biological activities and therapeutics of MSCs with respect to migration, homing to target site, adhesion, survival and reduced premature senescence. We discuss the application of the improved modified MSC in some selected human diseases. Possible ways of yet better enhancing the therapeutic outcome and overcoming challenges of MSC modification in the future are also elaborated. Conclusion: The importance of prosurvival and promigratory abilities of MSCs in their therapeutic applications can never be overemphasized. These abilities are maintained and even further enhanced via MSC modifications against the inhospitable microenvironment during culture and transplantation. This is a turning point in MSC-based therapy with promising preclinical studies and higher future prospect.

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Section: Improving Survivalmentioning

confidence: 99%

Improved therapeutics of modified mesenchymal stem cells: an update

Pei²,

et al. 2020

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“…Furthermore, the overexpression of integrin and focal adhesion complex by genetically modified MSCs increases by 1.5 times their survival, by fourfold their retention rate, and by 32% their adhesion to ischemic cardiomyocytes when compared to non-modified cells [ 53 ]. Also, the transplantation of pre-treated MSCs overexpressing Integrin-linked kinase improves their survival and angiogenic function [ 54 ]. Figure 2 showed the novel therapeutic strategies of MSC therapy.…”

Section: Mechanisms Of Action Of Msc Therapymentioning

confidence: 99%

Surfing the clinical trials of mesenchymal stem cell therapy in ischemic cardiomyopathy

et al. 2021

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While existing remedies failed to fully address the consequences of heart failure, stem cell therapy has been introduced as a promising approach. The present review is a comprehensive appraisal of the impacts of using mesenchymal stem cells (MSCs) in clinical trials mainly conducted on ischemic cardiomyopathy. The benefits of MSC therapy for dysfunctional myocardium are likely attributed to numerous secreted paracrine factors and immunomodulatory effects. The positive outcomes associated with MSC therapy are scar size reduction, reverse remodeling, and angiogenesis. Also, a decreasing in the level of chronic inflammatory markers of heart failure progression like TNF-α is observed. The intense inflammatory reaction in the injured myocardial micro-environment predicts a poor response of scar tissue to MSC therapy. Subsequently, the interval delay between myocardial injury and MSC therapy is not yet determined. The optimal requested dose of cells ranges between 100 to 150 million cells. Allogenic MSCs have different advantages compared to autogenic cells and intra-myocardial injection is the preferred delivery route. The safety and efficacy of MSCs-based therapy have been confirmed in numerous studies, however several undefined parameters like route of administration, optimal timing, source of stem cells, and necessary dose are limiting the routine use of MSCs therapeutic approach in clinical practice. Lastly, pre-conditioning of MSCs and using of exosomes mediated MSCs or genetically modified MSCs may improve the overall therapeutic effect. Future prospective studies establishing a constant procedure for MSCs transplantation are required in order to apply MSC therapy in our daily clinical practice and subsequently improving the overall prognosis of ischemic heart failure patients.

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“…Tumor angiogenesis and inflammation are important factors in cancer progression. Although there are few studies in colon cancer showing direct angiogenesis induction by ILK, one report has revealed that ILK overexpression regulates mesenchymal stem cell survival and angiogenesis via Akt and mTOR phosphorylation and VEGF expression ( Zeng et al, 2017 ). Another study showed that ILK overexpression in melanoma cells promotes angiogenesis of endothelial cells by activating the NF-κB/IL-6 signaling pathway in vitro and in vivo ( Wani et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

“…NF-κB and IL-6 and other inflammatory cytokines are also induced by ILK in experimental colitis and colorectal cancer ( Yan et al, 2014 ; Ahmed et al, 2017 ). Furthermore, a study has reported that the Akt-mTOR signaling pathway which is known to be regulated by ILK ( Zeng et al, 2017 ) is also involved in angiogenesis in colon cancer. For example, Cryptotanshinone, which is derived from Salvia miltiorrhiza Bunge , suppresses CT26 colon cancer cell angiogenesis via inhibiting the PI3K/Akt/mTOR signaling pathway, nuclear hypoxia inducible factor-1α (HIF-1α), VEGF and VEGFR gene activation ( Zhang et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

A Potential Role for Integrin-Linked Kinase in Colorectal Cancer Growth and Progression via Regulating Senescence and Immunity

et al. 2021

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Integrin-linked kinase (ILK) has been implicated as a molecular driver and mediator in both inflammation and tumorigenesis of the colon. ILK functions as an adaptor and mediator protein linking the extracellular matrix with downstream signaling pathways. ILK is broadly expressed in many human tissues and cells. It is also overexpressed in many cancers, including colorectal cancer (CRC). Inflammation, as evidenced by inflammatory bowel disease (IBD), is one of the highest risk factors for initiating CRC. This has led to the hypothesis that targeting ILK therapeutically could have potential in CRC, as it regulates different cellular processes associated with CRC development and progression as well as inflammation in the colon. A number of studies have indicated an ILK function in senescence, a cellular process that arrests the cell cycle while maintaining active metabolism and transcription. Senescent cells produce different secretions collectively known as the senescence-associated secretory phenotype (SASP). The SASP secretions influence infiltration of different immune cells, either positively for clearing senescent cells or negatively for promoting tumor growth, reflecting the dual role of senescence in cancer. However, a role for ILK in senescence and immunity in CRC remains to be determined. In this review, we discuss the possible role for ILK in senescence and immunity, paying particular attention to the relevance of ILK in CRC. We also examine how activating Toll-like receptors (TLRs) and their agonists in CRC could trigger immune responses against cancer, as a combination therapy with ILK inhibition.

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ILK regulates MSCs survival and angiogenesis partially through AKT and mTOR signaling pathways

Cited by 20 publications

References 26 publications

Improved therapeutics of modified mesenchymal stem cells: an update

Improved therapeutics of modified mesenchymal stem cells: an update

Surfing the clinical trials of mesenchymal stem cell therapy in ischemic cardiomyopathy

A Potential Role for Integrin-Linked Kinase in Colorectal Cancer Growth and Progression via Regulating Senescence and Immunity

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