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Stem cell homing and mobilization to and from the bone marrow endosteum. HSC mobilization and homing are mirror processes that strongly depend on the activation state of cell-cell contacts and the SDF-1α/ CXCR4 axis. HSC mobilization from bone marrow mediated by cytokines, e.g. G-CSF or chemokines such as IL-8 is caused by proteases (MMPs, elastase, and cathepsin G) that degrades adhesion molecules, membrane bound c-kit, and SDF-1α and its receptor CXCR4. In contrast, up-regulation of cell adhesion molecules and activation of the SDF-1α/ CXCR4 axis is essential for stem cell homing. The blue coloring represents the SDF-1α gradient in the bone marrow.
Source publication
Migration is an innate and fundamental cellular function that enables hematopoietic stem cells (HSCs) and endothelial progenitors (EPCs) to leave the bone marrow, relocate to distant tissue, and to return to the bone marrow. An increasing number of studies demonstrate the widening scope of the therapeutic potential of both HSCs and endothelial cell...
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The endothelial progenitor cells (EPCs) are angiogenic cells having properties similar to those of embryonal angioblasts. The number and function of EPCs are affected by a variety of conditions, including cytokines and chemokines, which are pivotal inflammatory signaling molecules. The purpose of this paper is to review current knowledge about the...
Citations
... The mobilization of MSCs subsequently secrete VEGF and SDF-1α factors in tissues, which can induce the formation of blood vessels [53]. Additionally, matrix metalloproteinase (MMP-2/9) activities also regulated cell migration and differentiation ability [54]. In line with our results, Pul-Col-Au nanocomposites induced the expression of the CXCR4/ SDF-1α axis, and matrix metalloproteinase (MMP-2/9) activities for MSC and HSF migration ( Figure 6 and Figure S6). ...
Tissue repair engineering supported by nanoparticles and stem cells has been demonstrated as being an efficient strategy for promoting the healing potential during the regeneration of damaged tissues. In the current study, we prepared various nanomaterials including pure Pul, pure Col, Pul–Col, Pul–Au, Pul–Col–Au, and Col–Au to investigate their physicochemical properties, biocompatibility, biological functions, differentiation capacities, and anti-inflammatory abilities through in vitro and in vivo assessments. The physicochemical properties were characterized by SEM, DLS assay, contact angle measurements, UV-Vis spectra, FTIR spectra, SERS, and XPS analysis. The biocompatibility results demonstrated Pul–Col–Au enhanced cell viability, promoted anti-oxidative ability for MSCs and HSFs, and inhibited monocyte and platelet activation. Pul–Col–Au also induced the lowest cell apoptosis and facilitated the MMP activities. Moreover, we evaluated the efficacy of Pul–Col–Au in the enhancement of neuronal differentiation capacities for MSCs. Our animal models elucidated better biocompatibility, as well as the promotion of endothelialization after implanting Pul–Col–Au for a period of one month. The above evidence indicates the excellent biocompatibility, enhancement of neuronal differentiation, and anti-inflammatory capacities, suggesting that the combination of pullulan, collagen, and Au nanoparticles can be potential nanocomposites for neuronal repair, as well as skin tissue regeneration in any further clinical treatments.
... SDF-1α/CXCR4 pathways and matrix metalloproteinase (MMP-2/9) activities regulated stem cell migration and differentiation capacity [65]. A study demonstrated that the effect of PEGylated hollow gold nanoparticles (HGNs) could significantly enhance stem cell migration. ...
A nanocomposite composed of polyethylene glycol (PEG) incorporated with various concentrations (~17.4, ~43.5, ~174 ppm) of gold nanoparticles (Au) was created to investigate its biocompatibility and biological performance in vitro and in vivo. First, surface topography and chemical composition was determined through UV-visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), scanning electron microscopy (SEM), free radical scavenging ability, and water contact angle measurement. Additionally, the diameters of the PEG-Au nanocomposites were also evaluated through dynamic light scattering (DLS) assay. According to the results, PEG containing 43.5 ppm of Au demonstrated superior biocompatibility and biological properties for mesenchymal stem cells (MSCs), as well as superior osteogenic differentiation, adipocyte differentiation, and, particularly, neuronal differentiation. Indeed, PEG-Au 43.5 ppm induced better cell adhesion, proliferation and migration in MSCs. The higher expression of the SDF-1α/CXCR4 axis may be associated with MMPs activation and may have also promoted the differentiation capacity of MSCs. Moreover, it also prevented MSCs from apoptosis and inhibited macrophage and platelet activation, as well as reactive oxygen species (ROS) generation. Furthermore, the anti-inflammatory, biocompatibility, and endothelialization capacity of PEG-Au was measured in a rat model. After implanting the nanocomposites into rats subcutaneously for 4 weeks, PEG-Au 43.5 ppm was able to enhance the anti-immune response through inhibiting CD86 expression (M1 polarization), while also reducing leukocyte infiltration (CD45). Moreover, PEG-Au 43.5 ppm facilitated CD31 expression and anti-fibrosis ability. Above all, the PEG-Au nanocomposite was evidenced to strengthen the differentiation of MSCs into various cells, including fat, vessel, and bone tissue and, particularly, nerve cells. This research has elucidated that PEG combined with the appropriate amount of Au nanoparticles could become a potential biomaterial able to cooperate with MSCs for tissue regeneration engineering.
... For efficient use in human therapy, SCs have to pos sess specific properties such as (i) maximal targeted effi cacy with the minimal adverse effects; (ii) when used as a vehicle, ability to preserve the efficacy and specificity of the carrying agent and to provide targeted delivery and release at the site of action [29 31]. The advantage of SCs in comparison to traditional therapy is the possibility of directed migration [32], local neuroprotection and regen eration, and immune regulation [33 38]. ...
The effects of systemic and intracerebral transplantation of human fetal neural stem and progenitor cells were studied on the model of olfactory bulbectomy in mice with developing signs of sporadic Alzheimer's disease. It was found that transplantation of these cells at certain stages of disease development contributed to improvement of spatial memory and preservation of hippocampal neurons in these animals.
... For efficient use in human therapy, SCs have to pos sess specific properties such as (i) maximal targeted effi cacy with the minimal adverse effects; (ii) when used as a vehicle, ability to preserve the efficacy and specificity of the carrying agent and to provide targeted delivery and release at the site of action [29 31]. The advantage of SCs in comparison to traditional therapy is the possibility of directed migration [32], local neuroprotection and regen eration, and immune regulation [33 38]. ...
It had been commonly believed for a long time, that once established, degeneration of the central nervous system (CNS) is irreparable, and that adult person merely cannot restore dead or injured neurons. The existence of stem cells (SCs) in the mature brain, an organ with minimal regenerative ability, had been ignored for many years. Currently accepted that specific structures of the adult brain contain neural SCs (NSCs) that can self–renew and generate terminally differentiated brain cells, including neurons and glia. However, their contribution to the regulation of brain activity and brain regeneration in natural aging and pathology is still a subject of ongoing studies. Since the 1970s, when Fuad Lechin suggested the existence of repair mechanisms in the brain, new exhilarating data from scientists around the world have expanded our knowledge on the mechanisms implicated in the generation of various cell phenotypes supporting the brain, regulation of brain activity by these newly generated cells, and participation of SCs in brain homeostasis and regeneration. The prospects of the SC research are truthfully infinite and hitherto challenging to forecast. Once researchers resolve the issues regarding SC expansion and maintenance, the implementation of the SC–based platform could help to treat tissues and organs impaired or damaged in many devastating human diseases. Over the past 10 years, the number of studies on SCs has increased exponentially, and we have already become witnesses of crucial discoveries in SC biology. Comprehension of the mechanisms of neurogenesis regulation is essential for the development of new therapeutic approaches for currently incurable neurodegenerative diseases and neuroblastomas. In this review, we present the latest achievements in this fast–moving field and discuss essential aspects of NSC biology, including SC regulation by hormones, neurotransmitters, and transcription factors, along with the achievements of genetic and chemical reprogramming for the safe use of SCs in vitro and in vivo.
... For efficient use in human therapy, SCs have to pos sess specific properties such as (i) maximal targeted effi cacy with the minimal adverse effects; (ii) when used as a vehicle, ability to preserve the efficacy and specificity of the carrying agent and to provide targeted delivery and release at the site of action [29 31]. The advantage of SCs in comparison to traditional therapy is the possibility of directed migration [32], local neuroprotection and regen eration, and immune regulation [33 38]. ...
It had been commonly believed for a long time, that once established, degeneration of the central nervous system (CNS) is irreparable, and that adult person merely cannot restore dead or injured neurons. The existence of stem cells (SCs) in the mature brain, an organ with minimal regenerative ability had been ignored for many years. Currently accepted that specific structures of the adult brain contain neural SCs (NSCs) that can self�renew and generate terminally differentiated brain cells, including neurons and glia. However, their contribution to the regulation of brain activity and brain regeneration in natural aging and pathology is still a subject of ongoing studies. Since the 1970s, when Fuad Lechin suggested the existence of repair mechanisms in the brain, new exhilarating data from scientists around the world has expanded our knowledge on the mechanisms implicated in the generation of various cell phenotypes supporting the brain, regulation of brain activity by these newly generated cells, and participation of SCs in brain homeostasis and regeneration. The prospects of the SC research are truthfully infinite and hitherto challenging to forecast. Once researchers resolve the issues regarding SC expansion and maintenance, the implementation of the SC-based platform could help to treat tissues and organs impaired or damaged in many devastating human diseases. Over the past 10 years, the number of studies on SCs has increased exponentially, and we have already become witnesses of crucial discoveries in SC biology. Comprehension of the mechanisms of neurogenesis regulation is essential for the development of new therapeutic approaches for currently incurable neurodegenerative diseases and neuroblastomas. In this review, we present the latest achievements in this fast-moving field and discuss essential aspects of NSC biology, including SC regulation by hormones, neurotransmitters, and transcription factors, along with the achievements of genetic and chemical reprogramming for the safe use of SCs in vitro and in vivo.
... Based upon our previous studies examining lung epithelial repair mechanisms [16][17][18]23 and other studies demonstrating interactions in progenitor B cells 24,25 , we hypothesized that CXCR4 signaling interacted with FAK during cell migration, and our results demonstrated an increase in association between CXCR4 and FAK in a population of cells enriched in migrating cells (Fig. 1). CXCR4 is a ubiquitous chemokine receptor that is involved in the activation of actin polymerization and initiation of cell migration in different types of cells, including ATII cells [33][34][35] . We previously showed that both inhibition and decreased expression of CXCR4 led to significant inhibition of cell migration in scratch wound models 23 . ...
Alveolar type II epithelial cells (ATII) are instrumental in early wound healing in response to lung injury, restoring epithelial integrity through spreading and migration. We previously reported in separate studies that focal adhesion kinase-1 (FAK) and the chemokine receptor CXCR4 promote epithelial repair mechanisms. However, potential interactions between these two pathways were not previously considered. In the present study, we found that wounding of rat ATII cells promoted increased association between FAK and CXCR4. In addition, protein phosphatase-5 (PP5) increased its association with this heteromeric complex, while apoptosis signal regulating kinase-1 (ASK1) dissociated from the complex. Cell migration following wounding was decreased when PP5 expression was decreased using shRNA, but migration was increased in ATII cells isolated from ASK1 knockout mice. Interactions between FAK and CXCR4 were increased upon depletion of ASK1 using shRNA in MLE-12 cells, but unaffected when PP5 was depleted. Furthermore, we found that wounded rat ATII cells exhibited decreased ASK1 phosphorylation at Serine-966, decreased serine phosphorylation of FAK, and decreased association of phosphorylated ASK1 with FAK. These changes in phosphorylation were dependent upon expression of PP5. These results demonstrate a unique molecular complex comprising CXCR4, FAK, ASK1, and PP5 in ATII cells during wound healing.
... In the following for transendothelia migration directed by chemokine gradient for HSPC homing process, the tissues should be destroyed; for example BM, spleen, bone marrow barrier and even blood; so several cytokines and chemokines are released to repair the destroyed tissues, so both repairing and homing are significant. There have been numerous reviews about HSPCs homing (9)(10)(11)(12)(13)(14)(15)(16)(17)(18).Homing is identified as the early event that lodges and firmly retains HSPCs in the BM prior to their proliferation and expansion (16). Homing occurs when HSPCs are intravenously administered to interact with the micro vascular endothelial cells of the BM, adhere to the vessel wall with sufficient strength to overcome the considerable shear stress exerted by the flowing blood. ...
Hematopoietic stem and progenitor cells (HSPCs) are non-stop travelers throughout body in both time and space. Understanding the mechanism of HSPCs homing and mobilization is important to enhance the efficacy at bone marrow transplantation and cellular therapy. Mobilized HSPCs has largely replaced than the use of bone marrow as a source of stem cells for both allogeneic and autologous stem cell transplantation. This review describes the specific factors which play a key role in homing and mobilization of HSPCs, includes SDF-1 and its receptor CXCR4, proteases (MMPs and CPM). Moreover, chemokines inducing rapid HPSCs mobilization would be discussed. In this article we showed that many factors such as adhesion molecules and SDF-1/CXCR4 have critical roles in homing hematopoietic stem cells and G.CSF, MMPs, adhesion molecules and ROS involvement in mobilization of stem cells. According to above, we can be rich the peripheral blood of HSPCS using of this factors and antagonist for this receptors on the osteoblastic cells or/and HSPCs to bone marrow transplant.
... These findings suggest that PlGF may have an important if ill-defined role in normal ECFC vasoreparative function. The signalling and functional responses of ECFCs exposed to PlGF remains to be elucidated, especially in the context of vascular insufficiency and hypoxia encountered by cells as they home to areas of localised tissue damage [23]. In this study, we define the effects of acute and chronic hypoxia on ECFCs in the absence of other confounding factors. ...
Background
Endothelial colony-forming cells (ECFCs), also termed late outgrowth endothelial cells, are a well-defined circulating endothelial progenitor cell type with an established role in vascular repair. ECFCs have clear potential for cell therapy to treat ischaemic disease, although the precise mechanism(s) underlying their response to hypoxia remains ill-defined. Methods
In this study, we isolated ECFCs from umbilical cord blood and cultured them on collagen. We defined the response of ECFCs to 1% O2 exposure at acute and chronic time points. ResultsIn response to low oxygen, changes in ECFC cell shape, proliferation, size and cytoskeleton phenotype were detected. An increase in the number of senescent ECFCs also occurred as a result of long-term culture in 1% O2. Low oxygen exposure altered ECFC migration and tube formation in Matrigel®. Increases in angiogenic factors secreted from ECFCs exposed to hypoxia were also detected, in particular, after treatment with placental growth factor (PlGF). Exposure of cells to agents that stabilise hypoxia-inducible factors such as dimethyloxalylglycine (DMOG) also increased PlGF levels. Conditioned medium from both hypoxia-treated and DMOG-treated cells inhibited ECFC tube formation. This effect was reversed by the addition of PlGF neutralising antibody to the conditioned medium, confirming the direct role of PlGF in this effect. Conclusions
This study deepens our understanding of the response of ECFCs to hypoxia and also identifies a novel and important role for PlGF in regulating the vasculogenic potential of ECFCs.
... SDF-1 represents a major chemokine for initiating endothelial progenitor cell migration and homing to ischemic tissues [19,20]. Platelets are a major source of SDF-1 and platelet expression levels of SDF-1 are upregulated in the patients with ACS [11,21,22]. ...
Platelet surface expression levels of stromal cell derived factor 1 (SDF-1) are elevated in acute coronary syndrome and associated with LVEF% improvement after myocardial infarction (MI). Platelet SDF-1 might facilitate thrombus formation and endomyocardial expression of SDF-1 is enhanced in inflammatory cardiomyopathy and positively correlates with myocardial fibrosis. The influence of platelet SDF-1 on outcome in the patients with symptomatic coronary artery disease (CAD) is to the best of our knowledge unknown.
Blood samples of 608 consecutive CAD patients were collected during the percutaneous coronary intervention and analyzed for surface expression of SDF-1 by flow cytometry. The primary combined endpoint was defined as the composite of either MI, or ischemic stroke, or all-cause death. Secondary endpoints were defined as the aforementioned single events. The patients with baseline platelet SDF-1 levels above the third quartile showed a significantly worse cumulative event-free survival when compared to the patients with lower baseline SDF-1 levels (first to third quartile) (log rank 0.009 for primary combined endpoint and log rank 0.016 for secondary endpoint all-cause death). Multivariate Cox regression analysis showed that SDF-1 levels above the third quartile were independently associated with the primary combined endpoint and the secondary endpoint all-cause death.
We provide first clinical evidence that high platelet expression levels of SDF-1 influence clinical outcomes in CAD patients in a negative way.
... Inhibition of the SDF-1receptor (CXCR4) improves the lung and heart dynamics in PH (Young et al., 2009;Savai et al., 2012). G-CSF, which is primarily expressed at the injured site, also mobilizes the stem/progenitor cells (Weidt et al., 2007). Our results suggest that ASCs or CM treatment could have either directly inhibited those cytokines or repaired the tissue injury associated with the PH lung or heart, thus minimizing the stimulus to recruit body's defence systems. ...
Background and purpose:
Pulmonary hypertension (PH) and pulmonary fibrosis (PF) are life threatening cardiopulmonary diseases. Existing pharmacological interventions have failed to improve clinical outcomes or reduce disease-associated mortality. Emerging evidence suggests that stem cells offer an effective treatment approach against various pathological conditions. It has been proposed that their beneficial actions may be mediated via secretion of paracrine factors. Herein, we evaluated the therapeutic potential of conditioned media (CM) from adipose stem cells (ASCs) against experimental models of PH and PF.
Experimental approach:
Monocrotaline (MCT) or bleomycin (Bleo) was injected into male Sprague-Dawley rats to induce PH or PF respectively. A subset of MCT and Bleo animals were treated with ASCs or CM. Echocardiographic and haemodynamic measurements were performed at the end of the study. Lung and heart tissues were harvested for RNA, protein and histological measurements.
Key results:
CM treatment attenuated MCT-induced PH by improving pulmonary blood flow and inhibiting cardiac remodelling. Further, histological studies revealed that right ventricular fibrosis, pulmonary vessel wall thickness and pericyte distribution were significantly decreased by CM administration. Likewise, CM therapy arrested the progression of PF in the Bleo model by reducing collagen deposition. Elevated expression of markers associated with tissue remodelling and inflammation were significantly reduced in both PF and PH lungs. Similar results were obtained with ASCs administration.
Conclusions and implications:
Our study indicates that CM treatment is as effective as ASCs in treating PH and PF. These beneficial effects of CM may provide an innovative approach to treat cardiopulmonary disorders.
