scholarly journals FoxC1-Induced Vascular Niche Improves Survival and Myocardial Repair of Mesenchymal Stem Cells in Infarcted Hearts

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Lan Zhao ◽  
Rui Zhang ◽  
Feng Su ◽  
Libing Dai ◽  
Jiahong Wang ◽  
...  

Aims. Forkhead box C1 (FoxC1) is essential for maintaining the hair follicle stem cell niche. The role of FoxC1 in maintaining mesenchymal stem cell (MSC) niches after myocardial infarction (MI) has not been directly determined to date. In this study, we determined to explore the possible roles and mechanisms of FoxC1 on MSC survival and function in the ischemic niche. Methods and Results. MI model was established in this study, and expression level of FoxC1 was overexpressed or knocked down through efficient delivery of FoxC1 transfection or siFoxC1. Fifteen days later, the animals were allocated randomly to receive phosphate-buffered saline (PBS) injection or MSC transplantation. We identified FoxC1 as a key regulator of maintaining the vascular niche in the infarcted hearts (IHs) by driving proangiogenic and anti-inflammatory cytokines while repressing inflammatory and fibrotic factor expression. This vascular niche improved MSC survival and capacity in the IHs. Importantly, FoxC1 interacted with MSCs and was required for vessel specification and differentiation of engrafted MSCs in the ischemic niches, promoting myocardial repair. Inhibiting FoxC1 abolished these effects. Conclusion. These results definitively implicate FoxC1 signaling in maintaining ischemic vascular niche, which may be helpful in myocardial repair induced by MSC therapy.

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Katie Joanna Lee ◽  
Peter David Clegg ◽  
Eithne Josephine Comerford ◽  
Elizabeth Gail Canty-Laird

Ligament is prone to injury and degeneration and has poor healing potential and, with currently ineffective treatment strategies, stem cell therapies may provide an exciting new treatment option. Ligament-derived stem cell (LDSC) populations have been isolated from a number of different ligament types with the majority of studies focussing on periodontal ligament. To date, only a few studies have investigated LDSC populations in other types of ligament, for example, intra-articular ligaments; however, this now appears to be a developing field. This literature review aims to summarise the current information on nondental LDSCs includingin vitrocharacteristics of LDSCs and their therapeutic potential. The stem cell niche has been shown to be vital for stem cell survival and function in a number of different physiological systems; therefore, the LDSC niche may have an impact on LDSC phenotype. The role of the LDSC niche on LDSC viability and function will be discussed as well as the therapeutic potential of LDSC niche modulation.


Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1002
Author(s):  
Fabiola Marino ◽  
Mariangela Scalise ◽  
Eleonora Cianflone ◽  
Luca Salerno ◽  
Donato Cappetta ◽  
...  

Over the years strong evidence has been accumulated showing that aerobic physical exercise exerts beneficial effects on the prevention and reduction of cardiovascular risk. Exercise in healthy subjects fosters physiological remodeling of the adult heart. Concurrently, physical training can significantly slow-down or even reverse the maladaptive pathologic cardiac remodeling in cardiac diseases, improving heart function. The underlying cellular and molecular mechanisms of the beneficial effects of physical exercise on the heart are still a subject of intensive study. Aerobic activity increases cardiovascular nitric oxide (NO) released mainly through nitric oxidase synthase 3 activity, promoting endothelium-dependent vasodilation, reducing vascular resistance, and lowering blood pressure. On the reverse, an imbalance between increasing free radical production and decreased NO generation characterizes pathologic remodeling, which has been termed the “nitroso-redox imbalance”. Besides these classical evidence on the role of NO in cardiac physiology and pathology, accumulating data show that NO regulate different aspects of stem cell biology, including survival, proliferation, migration, differentiation, and secretion of pro-regenerative factors. Concurrently, it has been shown that physical exercise generates physiological remodeling while antagonizes pathologic remodeling also by fostering cardiac regeneration, including new cardiomyocyte formation. This review is therefore focused on the possible link between physical exercise, NO, and stem cell biology in the cardiac regenerative/reparative response to physiological or pathological load. Cellular and molecular mechanisms that generate an exercise-induced cardioprotective phenotype are discussed in regards with myocardial repair and regeneration. Aerobic training can benefit cells implicated in cardiovascular homeostasis and response to damage by NO-mediated pathways that protect stem cells in the hostile environment, enhance their activation and differentiation and, in turn, translate to more efficient myocardial tissue regeneration. Moreover, stem cell preconditioning by and/or local potentiation of NO signaling can be envisioned as promising approaches to improve the post-transplantation stem cell survival and the efficacy of cardiac stem cell therapy.


2019 ◽  
Vol 38 (19) ◽  
Author(s):  
Daniel Peña‐Jimenez ◽  
Silvia Fontenete ◽  
Diego Megias ◽  
Coral Fustero‐Torre ◽  
Osvaldo Graña‐Castro ◽  
...  

2022 ◽  
pp. 1-10
Author(s):  
Patrick Wuchter ◽  
Anke Diehlmann ◽  
Harald Klüter

<b><i>Background:</i></b> The stem cell niche in human bone marrow provides scaffolds, cellular frameworks and essential soluble cues to support the stemness of hematopoietic stem and progenitor cells (HSPCs). To decipher this complex structure and the corresponding cellular interactions, a number of in vitro model systems have been developed. The cellular microenvironment is of key importance, and mesenchymal stromal cells (MSCs) represent one of the major cellular determinants of the niche. Regulation of the self-renewal and differentiation of HSPCs requires not only direct cellular contact and adhesion molecules, but also various cytokines and chemokines. The C-X-C chemokine receptor type 4/stromal cell-derived factor 1 axis plays a pivotal role in stem cell mobilization and homing. As we have learned in recent years, to realistically simulate the physiological in vivo situation, advanced model systems should be based on niche cells arranged in a three-dimensional (3D) structure. By providing a dynamic rather than static setup, microbioreactor systems offer a number of advantages. In addition, the role of low oxygen tension in the niche microenvironment and its impact on hematopoietic stem cells need to be taken into account and are discussed in this review. <b><i>Summary:</i></b> This review focuses on the role of MSCs as a part of the bone marrow niche, the interplay between MSCs and HSPCs and the most important regulatory factors that need to be considered when engineering artificial hematopoietic stem cell niche systems. <b><i>Conclusion:</i></b> Advanced 3D model systems using MSCs as niche cells and applying microbioreactor-based technology are capable of simulating the natural properties of the bone marrow niche more closely than ever before.


2020 ◽  
Author(s):  
Abid Hussain ◽  
Leila El Kebriti ◽  
Virginie Deleuze ◽  
Yaël Glasson ◽  
Nelly Pirot ◽  
...  

ABSTRACTLymphoblastic leukemia-derived sequence 1 (Lyl1) encodes a hematopoietic- and endothelial-specific transcriptional factor. Lyl1-deficient mice are viable, but they display mild hematopoietic and vascular defects. Here, we report that young Lyl1-/- mice exhibit transient obesity associated with general expansion of adipose tissues and unrelated to food intake. The increased fat tissue development in Lyl1-/- mice resulted from an earlier adipocyte differentiation of adipose stem cells (ASCs) through non-cell autonomous mechanisms. Specifically, we found that in Lyl1-/- mice, the vascular structures of adipose tissues are unstable, more prone to angiogenesis and, consequently, cannot maintain adipose progenitors in the niche vessel wall. Together, our data show that in Lyl1-/- mice, the impaired vascular compartment of the adipose niche promotes uncontrolled ASC activation and differentiation, leading to early adipocyte expansion and premature depletion of ASCs. Our study highlights the major structural role of the adipose tissue vascular niche in coordinating stem cell self-renewal and differentiation into adipocytes.


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