Multiprotein collagen/keratin hydrogel promoted myogenesis and angiogenesis of injured skeletal muscles in a mouse model.

Volumetric loss is one of the challenging issues in muscle tissue structure that causes functio laesa. Tissue engineering of muscle tissue using suitable hydrogels is an alternative to restoring the physiological properties of the injured area. Here, myogenic properties of type I collagen (0.5%) and keratin (0.5%) were investigated in a mouse model of biceps femoris injury. Using FTIR, gelation time, and rheological analysis, the physicochemical properties of the collagen (Col)/Keratin scaffold were analyzed. Mouse C2C12 myoblast-laden Col/Keratin hydrogels were injected into the injury site and histological examination plus western blotting were performed to measure myogenic potential after 15 days. FTIR indicated an appropriate interaction between keratin and collagen. The blend of Col/Keratin delayed gelation time when compared to the collagen alone group. Rheological analysis revealed decreased stiffening in blended Col/Keratin hydrogel which is favorable for the extrudability of the hydrogel. Transplantation of C2C12 myoblast-laden Col/Keratin hydrogel to injured muscle tissues led to the formation of newly generated myofibers compared to cell-free hydrogel and collagen groups (p < 0.05). In the C2C12 myoblast-laden Col/Keratin group, a low number of CD31+ cells with minimum inflammatory cells was evident. Western blotting indicated the promotion of MyoD in mice that received cell-laden Col/Keratin hydrogel compared to the other groups (p < 0.05). Despite the increase of the myosin cell-laden Col/Keratin hydrogel group, no significant differences were obtained related to other groups (p > 0.05). The blend of Col/Keratin loaded with myoblasts provides a suitable myogenic platform for the alleviation of injured muscle tissue.

Exosome-bearing hydrogels and cardiac tissue regeneration.

BACKGROUND: In recent years, cardiovascular disease in particular myocardial infarction (MI) has become the predominant cause of human disability and mortality in the clinical setting. The restricted capacity of adult cardiomyocytes to proliferate and restore the function of infarcted sites is a challenging issue after the occurrence of MI. The application of stem cells and byproducts such as exosomes (Exos) has paved the way for the alleviation of cardiac tissue injury along with conventional medications in clinics. However, the short lifespan and activation of alloreactive immune cells in response to Exos and stem cells are the main issues in patients with MI. Therefore, there is an urgent demand to develop therapeutic approaches with minimum invasion for the restoration of cardiac function. MAIN BODY: Here, we focused on recent data associated with the application of Exo-loaded hydrogels in ischemic cardiac tissue. Whether and how the advances in tissue engineering modalities have increased the efficiency of whole-based and byproducts (Exos) therapies under ischemic conditions. The integration of nanotechnology and nanobiology for designing novel smart biomaterials with therapeutic outcomes was highlighted. CONCLUSION: Hydrogels can provide suitable platforms for the transfer of Exos, small molecules, drugs, and other bioactive factors for direct injection into the damaged myocardium. Future studies should focus on the improvement of physicochemical properties of Exo-bearing hydrogel to translate for the standard treatment options.

Phenolated alginate hydrogel induced osteogenic properties of mesenchymal stem cells via Wnt signaling pathway.

Osteogenic properties of phenolated alginate (1.2 %) hydrogel containing collagen (0.5 %)/nano-hydroxyapatite (1 %) were studied on human mesenchymal stem cells in vitro. The phenolation rate and physical properties of the hydrogel were assessed using nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FTIR), Scanning electron microscope (SEM), swelling ratio, gelation time, mechanical assay, and degradation rate. The viability of encapsulated cells was monitored on days 7, 14, and 21 using an MTT assay. Osteoblast differentiation was studied using western blotting, and real-time PCR. Using PCR array analysis, the role of the Wnt signaling pathway was also investigated. Data showed that the combination of alginate/collagen/nanohydroxyapatite yielded proper mechanical features. The addition of nanohydroxyapatite, and collagen reduced degradation, swelling rate coincided with increased stiffness. Elasticity and pore size were also diminished. NMR and FTIR revealed suitable incorporation of collagen and nanohydroxyapatite in the structure of alginate. Real-time PCR analysis and western blotting indicated the expression of osteoblast-related genes such as Runx2 and osteocalcin. PCR array revealed the induction of numerous genes related to Wnt signaling pathways during the maturation of human stem cells toward osteoblast-like cells. In vivo data indicated that transplantation of phenolated alginate/collagen/nanohydroxyapatite hydrogel led to enhanced de novo bone formation in rats with critical-sized calvarial defects. Phenolated alginate hydrogel can promote the osteogenic capacity of human amniotic membrane mesenchymal stem cells in the presence of nanohydroxyapatite and collagen via engaging the Wnt signaling pathway.

Polyurethane-based nanofibrous mat containing porphyrin with photosensitivity and bactericidal properties can promote cutaneous tissue healing in rats.

The regeneration of cutaneous tissue is one of the most challenging issues in human regenerative medicine. To date, several studies have been done to promote cutaneous tissue healing with minimum side effects. The healing potential of polyurethane (PU)/Poly (caprolactone)-poly (ethylene glycol)-poly (caprolactone) (PCEC)/chitosan (CS) (PCS) nanofibrous mat with cationic photosensitizer meso tetrakis (N-methyl pyridinium-4-yl) porphyrin tetratosylate salt (TMP) was examined. The CS tripolyphosphate nanoparticles (CSNPs) were prepared and loaded by TMP to provide an efficient drug release system (TMPNPs) for delivery of TMP to promote wound healing. In in vitro setting, parameters such as bactericidal effects, cytocompatibility, and hemolytic effects were examined. The healing potential of prepared nanofibrous mats was investigated in a rat model of full-thickness cutaneous injury. PCS/TMP/TMPNPs nanofibers can efficiently release porphyrin in the aqueous phase. The addition of TMPNPs and CS to the PU backbone increased the hydrophilicity, degradation, and reduced mechanical properties. The culture of human fetal foreskin fibroblasts (HFFF2) on PCS/TMP/TMPNPs scaffold led to an increased survival rate and morphological adaptation analyzed by MTT and SEM images. Irradiation with a red laser (635 nm, 3 J/cm2) for the 30 s reduced viability of S. aureus and E. Coli bacteria plated on PCS/TMP and PCS/TMP/TMPNPs nanofibrous mats compared to PU/PCEC (PC) and PU/PCEC/CS (PCS) groups, indicating prominent antibacterial effects of PCS/TMP and PCS/TMP/TMPNPs nanofibrous (p < 0.05). Data indicated that PCS/TMP/TMPNPs mat enhanced healing of the full-thickness excisional wound in a rat model by the reduction of inflammatory response and fibrotic changes compared to the PC, and PCS groups (p < 0.05). Immunofluorescence imaging indicated that levels of Desmoglein were increased in rats that received PCS/TMP/TMPNPs compared to the other groups. It is found that a PU-based nanofibrous mat is an appropriate scaffold to accelerate the healing of injured skin.

Exosome-loaded microneedle patches: Promising factor delivery route.

During the past decades, the advent of different microneedle patch (MNPs) systems paves the way for the targeted and efficient delivery of several growth factors into the injured sites. MNPs consist of several micro-sized (25-1500 µm) needle rows for painless delivery of incorporated therapeutics and increase of regenerative outcomes. Recent data have indicated the multifunctional potential of varied MNP types for clinical applications. Advances in the application of materials and fabrication processes enable researchers and clinicians to apply several MNP types for different purposes such as inflammatory conditions, ischemic disease, metabolic disorders, vaccination, etc. Exosomes (Exos) are one of the most interesting biological bioshuttles that participate in cell-to-cell paracrine interaction with the transfer of signaling biomolecules. These nano-sized particles, ranging from 50 to 150 nm, can exploit several mechanisms to enter the target cells and deliver their cargo into the cytosol. In recent years, both intact and engineered Exos have been increasingly used to accelerate the healing process and restore the function of injured organs. Considering the numerous benefits provided by MNPs, it is logical to hypothesize that the development of MNPs loaded with Exos provides an efficient therapeutic platform for the alleviation of several pathologies. In this review article, the authors collected recent advances in the application of MNP-loaded Exos for therapeutic purposes.

Tissue engineering modalities in skeletal muscles: focus on angiogenesis and immunomodulation properties.

Muscular diseases and injuries are challenging issues in human medicine, resulting in physical disability. The advent of tissue engineering approaches has paved the way for the restoration and regeneration of injured muscle tissues along with available conventional therapies. Despite recent advances in the fabrication, synthesis, and application of hydrogels in terms of muscle tissue, there is a long way to find appropriate hydrogel types in patients with congenital and/or acquired musculoskeletal injuries. Regarding specific muscular tissue microenvironments, the applied hydrogels should provide a suitable platform for the activation of endogenous reparative mechanisms and concurrently deliver transplanting cells and therapeutics into the injured sites. Here, we aimed to highlight recent advances in muscle tissue engineering with a focus on recent strategies related to the regulation of vascularization and immune system response at the site of injury.

Interaction of alginate with nano-hydroxyapatite-collagen using strontium provides suitable osteogenic platform.

BACKGROUND: Hydrogels based on organic/inorganic composites have been at the center of attention for the fabrication of engineered bone constructs. The establishment of a straightforward 3D microenvironment is critical to maintaining cell-to-cell interaction and cellular function, leading to appropriate regeneration. Ionic cross-linkers, Ca2+, Ba2+, and Sr2+, were used for the fabrication of Alginate-Nanohydroxyapatite-Collagen (Alg-nHA-Col) microspheres, and osteogenic properties of human osteoblasts were examined in in vitro and in vivo conditions after 21 days. RESULTS: Physicochemical properties of hydrogels illustrated that microspheres cross-linked with Sr2+ had reduced swelling, enhanced stability, and mechanical strength, as compared to the other groups. Human MG-63 osteoblasts inside Sr2+ cross-linked microspheres exhibited enhanced viability and osteogenic capacity indicated by mineralization and the increase of relevant proteins related to bone formation. PCR (Polymerase Chain Reaction) array analysis of the Wnt (Wingless-related integration site) signaling pathway revealed that Sr2+ cross-linked microspheres appropriately induced various signaling transduction pathways in human osteoblasts leading to osteogenic activity and dynamic growth. Transplantation of Sr2+ cross-linked microspheres with rat osteoblasts into cranium with critical size defect in the rat model accelerated bone formation analyzed with micro-CT and histological examination. CONCLUSION: Sr2+ cross-linked Alg-nHA-Col hydrogel can promote functionality and dynamic growth of osteoblasts.

Asthma can Promote Cardiomyocyte Mitophagy in a Rat Model.

Clinical observations have shown the risk of cardiovascular disease during asthmatic changes. Whether and how asthma causes heart failure is the subject of debate. Here, we aimed to investigate the possibility of cardiomyocyte mitophagy in a rat model of asthma. Twelve mature Wistar rats were randomly allocated into the Control and Asthmatic rats (n = 6). To induce asthma, ovalbumin was injected intraperitoneally on days 1 and 8 and procedure followed by nebulization from days 14 to 32. After 2 weeks, we performed the pathological examination of both lungs and heart using Hematoxylin-Eosin staining. Real-time PCR analysis was used to measure the expression of mitophagic factors, such as Optineurin, Pink1, and mitofusin 1 and 2. Typical changes like increased inter-alveolar septa thickness and interstitial pneumonia were evident in asthmatic lungs. In cardiac tissue, slight inflammatory response, and hydropic degeneration with an eosinophilic appearance were detected in the cytoplasm of cardiomyocytes. Real-time PCR analysis showed mitophagic response in pulmonary and cardiac tissues via upregulation of mitophagy-related genes like Optineurin and Pink-1 in asthmatic lungs and hearts compared to the control group (p < 0.05). Likewise, asthmatic changes increased the expression of genes associated with mitochondrial fusion in the lungs and heart. The expression of mitofusin1 and 2 was significantly increased following inflammatory response in pulmonary and cardiac tissues (p < 0.05). Our findings showed the expression of certain factors related to mitophagy during chronic asthmatic conditions. The findings open a new avenue in the understanding of cardiomyocyte injury during asthma.

Putative therapeutic impacts of cardiac CTRP9 in ischaemia/reperfusion injury.

Recently, cytokines belonging to C1q/tumour necrosis factor-related proteins (CTRPs) superfamily have attracted increasing attention due to multiple metabolic functions and desirable anti-inflammatory effects. These various molecular effectors exhibit key roles upon the onset of cardiovascular diseases, making them novel adipo/cardiokines. This review article aimed to highlight recent findings correlated with therapeutic effects and additional mechanisms specific to the CTRP9, particularly in cardiac ischaemia/reperfusion injury (IRI). Besides, the network of the CTPR9 signalling pathway and its possible relationship with IRI were discussed. Together, the discovery of all involved underlying mechanisms could shed light to alleviate the pathological sequelae after the occurrence of IRI.

Application of microneedle patches for drug delivery; doorstep to novel therapies.

In the past decade, microneedle-based drug delivery systems showed promising approaches to become suitable and alternative for hypodermic injections and can control agent delivery without side effects compared to conventional approaches. Despite these advantages, the procedure of microfabrication is facing some difficulties. For instance, drug loading method, stability of drugs, and retention time are subjects of debate. Besides, the application of novel refining fabrication methods, types of materials, and instruments are other issues that need further attention. Herein, we tried to summarize recent achievements in controllable drug delivery systems (microneedle patches) in vitro and in vivo settings. In addition, we discussed the influence of delivered drugs on the cellular mechanism and immunization molecular signaling pathways through the intradermal delivery route. Understanding the putative efficiency of microneedle patches in human medicine can help us develop and design sophisticated therapeutic modalities.

An Examination of the Putative Role of Melatonin in Exosome Biogenesis.

During the last two decades, melatonin has been found to have pleiotropic effects via different mechanisms on its target cells. Data are abundant for some aspects of the signaling pathways within cells while other casual mechanisms have not been adequately addressed. From an evolutionary perspective, eukaryotic cells are equipped with a set of interrelated endomembrane systems consisting of intracellular organelles and secretory vesicles. Of these, exosomes are touted as cargo-laden secretory vesicles that originate from the endosomal multivesicular machinery which participate in a mutual cross-talk at different cellular interfaces. It has been documented that cells transfer various biomolecules and genetic elements through exosomes to sites remote from the original cell in a paracrine manner. Findings related to the molecular mechanisms between melatonin and exosomal biogenesis and cargo sorting are the subject of the current review. The clarification of the interplay between melatonin and exosome biogenesis and cargo sorting at the molecular level will help to define a cell's secretion capacity. This review precisely addresses the role and potential significance of melatonin in determining the efflux capacity of cells via the exosomal pathway. Certain cells, for example, stem cells actively increase exosome efflux in response to melatonin treatment which accelerates tissue regeneration after transplantation into the injured sites.

Culture of rabbit bone marrow mesenchymal stem cells on polyurethane/pyrrole surface promoted differentiation into endothelial lineage.

Due to the electrical conductivity, pyrrole-based scaffolds are one of the attractive biomaterials in the regeneration of electrically active tissues like the heart and brain. Here, we investigated the impact of polyurethane/pyrrole scaffold on the angiogenesis differentiation of rabbit mesenchymal stem cells toward endothelial lineage in vitro. Nanoelectrospun polyurethane/pyrrole fibers were synthesized and characterized using attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectrum analysis, scanning electron microscope (SEM) imaging. Mechanical properties, electroconductivity, and hydrophobicity were also measured. The viability of cells was monitored 72 hours after being plated on the polyurethane/pyrrole surface. The endothelial differentiation of stem cells was explored using western blotting. ATR-FTIR revealed that the pyrrole was successfully polymerized to polypyrrole and blend with polyurethane fibers. The addition of pyrrole to polyurethane increased the tensile strength compared to the polyurethane group. These features coincided with the reduction of the hydrophilic properties of polyurethane. Based on our data, the electro-conductivity of polyurethane/pyrrole was superior compared to the polyurethane group. SEM imaging showed an appropriate cell attachment to the surface of polyurethane/pyrrole and polyurethane groups synthesized membranes. MTT assay revealed a significantly increased survival rate in the polyurethane/pyrrole group compared to the polyurethane group (P < .05). We noted a statistically significant increase of endothelial-associated proteins, CD31, von Willebrand factor, and CD34, in cells expanded on polyurethane/pyrrole compared to the polyurethane group (P < .05). As a more general note, it could be hypothesized that the polyurethane/pyrrole blend could improve the angiogenesis potency of rabbit bone marrow mesenchymal stem cells for regenerative purposes.

Distinct chemical composition and enzymatic treatment induced human endothelial cells survival in acellular ovine aortae.

OBJECTIVE: The current experiment aimed to assess the impact of detergents such as 3% Triton X-100, 1% peracetic acid, 1% Tween-20, and 1% SDS in combination with Trypsin-EDTA on acellularization of ovine aortae after 7 days. RESULTS: Hematoxylin-Eosin staining showed an appropriate acellularization rate in ovine aortae, indicated by a lack of cell nuclei in the tunica media layer. DAPI staining confirmed the lack of nuclei in the vascular wall after being exposed to the combination of chemical and enzymatic solutions. Verhoeff-Van Gieson staining showed that elastin fibers were diminished in acellular samples compared to the control group while collagen stands were unchanged. CCK-8 survival assay showed enhanced viability in human umbilical vein endothelial cells 5 days after being cultured on decellularized samples compared to the cells cultured on a plastic surface (p < 0.05). SEM imaging showed flattening of endothelial cells on the acellular surface.

A giant splenic hydatid cyst: Why calcified cysts should not be considered as a dead cyst.

Our case report showed that peripheral wall calcification of the hydatid cyst does not mean inactivation of the cyst and calcification of cyst wall may occur in all stages of disease.

Comparison of the Therapeutic Effects of a Pigtail Catheter and Chest Tube in the Treatment of Spontaneous Pneumothorax: A Randomized Clinical Trial Study.

OBJECTIVE: The purpose of this study was to compare the therapeutic effects of a pigtail catheter with a chest tube in the management of patients with spontaneous pneumothorax (SP). MATERIAL AND METHODS: A randomized controlled trial study was performed on patients with SP from August 2016 to December 2017 at Imam Reza Hospital, Tabriz, Iran. Forty-four patients were randomly assigned into 2 groups: group A with a 14-Fr pigtail catheter and group B using a 28-Fr chest tube. Two patients were excluded from the study. RESULTS: Forty-two patients participated in the study with 21 patients in each group. There were no significant differences between the groups in the patients' baseline data. The success rate was higher in patients with pigtail catheters (85.7%) than in patients with chest tubes (76.2%). However, the difference was not significant (P = .43). The procedure time was significantly shorter in the pigtail group compared to the chest tube group (P < .01). According to the visual analog scale (VAS), patients with pigtail catheters experienced milder pain during tube insertion than patients with chest tubes (P = .02). However, the pain score at the insertion site was not significantly different between the 2 groups for the first 2 days after the procedure. Patients with pigtail catheters experienced significantly less pain than patients with chest tubes during removal of the tube (P < .01). Also, there was no significant difference between the pain experienced by the 2 groups at the time of hospital discharge (P = .19). Analgesic drug usage was lower in patients with pigtail catheters compared to patients with chest tubes (P < .01). There was a trend toward lower median hospital stays demonstrated by patients with pigtail catheters compared to patients with chest tubes (P = .2). CONCLUSION: Pigtail catheters might be as effective as chest tubes for treating patients with SP in terms of lung re-expansion.

Comparison of end-to-side hand-sewn and side-to-side stapled cervical esophagogastric anastomosis in patients with lower thoracic esophageal cancer undergoing transhiatal esophagectomy: an Iranian retrospective cohort study.

BACKGROUND: Controversies in terms of efficacy and postoperative advantages surround stapled esophagogastric anastomosis compared with the hand-sewn technique as a treatment for patients with esophageal cancer. The purpose of this study was to compare the clinical outcomes of hand-sewn end-to-side esophago-gastrostomy and side-to-side stapled cervical esophagogastric anastomosis after esophagectomy for the aforementioned patients. METHODS: This retrospective cohort study involved examining the medical records of 433 patients who underwent transhiatal esophagectomy for esophageal cancer from March 2010 to March 2016. All the patients were operated using end-to-side hand-sewn esophago-gastrostomy and side-to-side stapled cervical esophagogastric anastomosis. 409 of the patients received a year's worth of follow-up evaluations. All the cases were revisited in 2 weeks as well as in four, eight, and 12 months after surgery. The patients were assessed in terms of postoperative outcomes, including reflux symptoms, anastomotic leakage and stricture, and the need for anastomotic dilatation. RESULTS: Hand-sewn anastomosis was carried out in 271 (62.5%) patients, whereas stapled anastomosis was performed in 162 (37.4%) patients. The mean operative times were 214.46 ± 84.33 min and 250.55 ± 43.31 min for the stapled and hand-sewn anastomosis groups, respectively (P = 0.028). The two groups showed no significant differences with respect to stays in intensive care units and hospitals. Postoperatively, 38 (14.67%) cases of anastomotic leakage were detected in the hand-sewn anastomosis group, with incidence being significantly higher than that in the stapled anastomosis group (8 cases or 5.33%; P = 0.002). Anastomotic stricture occurred less frequently in the patients who underwent stapled anastomosis (P = 0.004). Within the one-year follow-up period, the patients treated via hand-sewn anastomosis more frequently required anastomotic dilatation (P = 0.02). CONCLUSION: Side-to-side stapled cervical esophagogastric anastomosis may reduce operation times and decrease the rates of anastomotic leakage, anastomotic stricture, and anastomotic dilatation in patients with lower thoracic esophageal cancer undergoing transhiatal esophagectomy.

Cytoprotective and cytofunctional effect of polyanionic polysaccharide alginate and gelatin microspheres on rat cardiac cells.

This study investigated the cyto-functional effect of Alginate-Gelatin microspheres on rat cardiomyoblasts after 7 days. Rat cardiomyoblasts were encapsulated inside Alginate-Gelatin microspheres via application of high voltage rate and dropping in a stirring CaCl2 solution. The swelling rate, biodegradation, and mechanical features were measured. Cell viability was assessed using MTT. Cell membrane integrity was monitored via calculation supernatant SGOT, SGPT, CPK, and LDH. We also measured SOD, GPx, and anti-oxidant capacity. Protein levels of Nrf-2 and PCCG-1α were detected via western blotting. The cyto-functional activity of encapsulated cells was monitored using real-time PCR assay targeting the expression of Connexin-43, α-actinin, and myosin light chain. Data showed suitable biodegradation and swelling rate in Alginate-gelatin microspheres by time. 7-day incubation of rat cells inside microspheres did not exert cytotoxicity compared to control cells (p > 0.05). The release of SGPT, SGOT, CPK, and LDH in encapsulated cells was significantly decreased compared to the control group (p < 0.05). We also found enhanced anti-oxidant capacity and SOD and GPx activity in cells after being-encapsulated inside Alginate-Gelatin microspheres (p < 0.05) coincided with increased Nrf-2 synthesis (p < 0.05) compared to control cells. The expression of Connexin-43, α-actinin, and myosin light chain was significantly up-regulated, showing cyto-functional effect of Alginate-Gelatin microspheres after 7-days.

Developing a high-performance liquid chromatography fast and accurate method for quantification of silibinin.

OBJECTIVE: Silibinin is an antioxidant agent and is shown to have anticancer effects in different cancers including lung, breast, colorectal, liver, prostate, and kidney. There are challenges in the clinical use of silibinin. The main limitation is low solubility, poor oral absorption, and extensive hepatic metabolism. We aim to develop a High-Performance Liquid Chromatography (HPLC) sensitive method for quantification of silibinin in aqueous samples to quantify its concentration in new formulations. A reverse-phase high-performance liquid chromatography (RP-HPLC) composed of C18 column as stationary phase and the mixture of methanol (90%) and water (10%) as mobile phase. The developed method was validated based on the established guidelines. RESULTS: The retention time for silibinin was seen in 2.97 min after injection. The calibration curve was drawn and the established method demonstrated a linear ranged from 10 to 100 µg/ml, with a correlation coefficient of 0.996. The sensitivity of the developed method was 10 µg/ml. The accuracy calculated in the range of 88-105.9% and the precision (as relative standard deviation) was between 2.7 and 10.9%. These results demonstrate that the developed method can be a fast and accurate method for quantification of silibinin in aqueous samples.

Cardioprotective role of extracellular vesicles: A highlight on exosome beneficial effects in cardiovascular diseases.

Extracellular vesicles (EVs) are nano-sized vesicles, released from many cell types including cardiac cells, have recently emerged as intercellular communication tools in cell dynamics. EVs are an important mediator of signaling within cells that influencing the functional behavior of the target cells. In heart complex, cardiac cells can easily use EVs to transport bioactive molecules such as proteins, lipids, and RNAs to the regulation of neighboring cell function. Cross-talk between intracardiac cells plays pivotal roles in the heart homeostasis and in adaptive responses of the heart to stress. EVs were released by cardiomyocytes under baseline conditions, but stress condition such as hypoxia intensifies secretome capacity. EVs secreted by cardiac progenitor cells and cardiosphere-derived cells could be pinpointed as important mediators of cardioprotection and cardiogenesis. Furthermore, EVs from many different types of stem cells could potentially exert a therapeutic effect on the damaged heart. Recent evidence shows that cardiac-derived EVs are rich in microRNAs, suggesting a key role in the controlling of cellular processes. EVs harboring exosomes may be clinically useful in cell-free therapy approaches and potentially act as prognosis and diagnosis biomarkers of cardiovascular diseases.

Toll-like receptors in the functional orientation of cardiac progenitor cells.

Cardiac progenitor cells (CPCs) have the potential to differentiate into several cell lineages with the ability to restore in cardiac tissue. Multipotency and self-renewal activity are the crucial characteristics of CPCs. Also, CPCs have promising therapeutic roles in cardiac diseases such as valvular disease, thrombosis, atherosclerosis, congestive heart failure, and cardiac remodeling. Toll-like receptors (TLRs), as the main part of the innate immunity, have a key role in the development and differentiation of immune cells. Some reports are found regarding the effect of TLRs in the maturation of stem cells. This article tried to find the potential role of TLRs in the dynamics of CPCs. By showing possible crosstalk between the TLR signaling pathways and CPCs dynamics, we could achieve a better conception related to TLRs in the regeneration of cardiac tissue.