Cell Journal (Yakhteh)
Volume:24 Issue: 7, Jul 2022

Although recent progress in medicine has substantially reduced cardiovascular diseases (CVDs)-relatedmortalities, current therapeutics have failed miserably to be beneficial for all patients with CVDs. A wide array ofevidence suggests that newly-introduced cell-free treatments (CFT) have more reliable results in the improvementof cardiac function. The main regeneration activity of CFT protocols is based on bypassing cells and using paracrinefactors. In this article, we aim to compare various stem cell secretomes, a part of a CFT strategy, to generalize theireffective clinical outcomes for patients with CVDs. Data for this review article were collected from 70 published articles(original, review, randomized clinical trials (RCTs), and case reports/series studies done on human and animals)obtained from Cochrane, Science Direct, PubMed, Scopus, Elsevier, and Google Scholar) from 2015 to April 2020using six keywords. Full-text/full-length articles, abstract, section of book, chapter, and conference papers in Englishlanguage were included. Studies with irrelevant/insufficient/data, or undefined practical methods were excluded. CFTapproaches involved in growth factors (GFs); gene-based therapies; microRNAs (miRNAs); extracellular vesicles (EVs)[exosomes (EXs) and microvesicles (MVs)]; and conditioned media (CM). EXs and CM have shown more remarkableresults than stem cell therapy (SCT). GF-based therapies have useful results as well as side effects like pathologicangiogenesis side effect. Cell source, cell′s aging and CM affect secretomes. Genetic manipulation of stem cellscan change the secretome’s components. Growing progression to end stage heart failure (HF), propounds CFT asan advantageous method with practical and clinical values for replacement of injured myocardium, and induction ofneovascularization. To elucidate the secrets behind amplifying the expansion rate of cells, increasing life-expectancy,and improving quality of life (QOL) for patients with ischemic heart diseases (IHDs), collaboration among cell biologist,basic medical scientists, and cardiologists is highly recommended.

Extremely low-frequency magnetic field (ELF-MF) exposure, as a targeted tumor therapy, presents severalpotential advantages. In this research, we investigated effects of different ELF-MF intensities on cell viability and expression levels of the mammalian target of rapamycin (mTOR) and hsa_circ_100338 in the normal fibroblast (Hu02) and human gastric adenocarcinoma (AGS) cell lines.

In this experimental study, cell lines of AGS and Hu02, were cultured under the exposure of ELFMF with magnetic flux densities (MFDs) of 0.25, 0.5, 1 and 2 millitesla (mT) for 18 hours. The 3-(4, 5-dimethylthiazoyl-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay was used to evaluate the cell viability. Relative expression of mTOR and hsa_circ_100338 RNAs was estimated by quantitative real-time polymerase chain reaction (qRT-PCR) technique.

Viability of the normal cells was significantly increased at MFDs of 0.5, 1 and 2 mT, while viability of the tumor cells was significantly decreased at MFD of 0.25 and increased at MFD of 2 mT. Expression level of mTOR was significantly increased at the all applied MFDs in the normal cells, while it was significantly decreased at MFDs of 0.25 and 0.5mT in the tumor cells. MFDs of 1 and 2 mT in tumor cells inversely led to the increase in mTOR expression. hsa_circ_100338 was downregulated in MFD of 0.25 mT and then it was increased parallel to the increase of MFD in the normal and tumor cells.

Results of the present study indicated that ELF-MF at MFDs of 0.25 and 0.5 mT can lead to decrease in the both mTOR and hsa_circ_100338 expression levels. Given the role of mTOR in cell growth, proliferation and differentiation, in addition to the potential role of hsa_circ_100338 in metastasis, expression inhibition of these two genes could be a therapeutic target in cancer treatment.

Tendon repair strategies usually are accompanied by pathological mineralization and scar tissue formation that increases the risk of re-injuries. This study aimed to establish an efficient tendon regeneration method simultaneously with a reduced risk of ectopic bone formation.

In this experimental study, tenogenic differentiation was induced through transforming growth factor- β3 (TGFB3) treatment in combination with the inhibiting concentrations of bone morphogenetic proteins (BMP) antagonists, gremlin-2 (GREM2), and a Wnt inhibitor, namely sclerostin (SOST). The procedure’s efficacy was evaluated using real-time polymerase chain reaction (qPCR) for expression analysis of tenogenic markers and osteochondrogenic marker genes. The expression level of two tenogenic markers, SCX and MKX, was also evaluated by immunocytochemistry. Sirius Red staining was performed to examine the amounts of collagen fibers. Moreover, to investigate the impact of the substrate on tenogenic differentiation, the nanofibrous scaffolds that highly resemble tendon extracellular matrix was employed.

Aggregated features formed in spontaneous normal culture conditions followed by up-regulation of tenogenicand osteogenic marker genes, including SCX, MKX, COL1A1, RUNX2, and CTNNB1. TGFB3 treatment exaggeratedmorphological changes and markedly amplified tenogenic differentiation in a shorter period of time. Along with TGFB3 treatment, inhibition of BMPs by GREM2 and SOST delayed migratory events to some extent and dramatically reduced osteo-chondrogenic markers synergistically. Nanofibrous scaffolds increased tenogenic markers while declining the expression of osteo-chondrogenic genes.

These findings revealed an appropriate in vitro potential of spontaneous tenogenic differentiation of eq- ASCs that can be improved by simultaneous activation of TGFB and inhibition of osteoinductive signaling pathways.

The main objective of this study is to determine the myogenic effects of skeletal muscle extracellular matrix, vascular endothelial growth factor and human umbilical vein endothelial cells on adipose-derived stem cells to achieve a 3-dimensional engineered vascular-muscle structure.

The present experimental research was designed based on two main groups, i.e. monocultureof adipose tissue-derived stem cells (ADSCs) and co-culture of ADSCs and human umbilical vein endothelial cells ( HUVECs) in a ratio of 1:1. Skeletal muscle tissue was isolated, decellularized and its surface was electrospun using polycaprolactone/gelatin parallel nanofibers and then matrix topography was evaluated through H&E, trichrome staining and SEM. The expression of MyHC2 gene and tropomyosin protein were examined through real-time reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence, respectively. Finally, the morphology of mesenchymal and endothelial cells and their relationship with each other and with the engineered scaffold were examined by scanning electron microscopy (SEM).

According to H&E and Masson’s Trichrome staining, muscle tissue was completely decellularized. SEM showed parallel Polycaprolactone (PCL)/gelatin nanofibers with an average diameter of about 300 nm. The immunofluorescence proved that tropomyosin was positive in the ADSCs monoculture and the ADSCs/HUVECs coculture in horse serum (HS) and HS/VEGF groups. There was a significant difference in the expression of the MyHC2 gene between the ADSCs and ADSCs/HUVECs culture groups (P<0.05) and between the 2D and 3D models in HS/ VEGF differentiation groups (P<001). Moreover, a significant increase existed between the HS/VEGF group and other groups in terms of endothelial cells growth and proliferation as well as their relationship with differentiated myoblasts (P<0.05).

Co-culture of ADSCs/HUVECs on the engineered cell-free muscle scaffold and the dual effects of VEGF can lead to formation of a favorable engineered vascular-muscular tissue. These engineered structures can be used as an acceptable tool for tissue implantation in muscle injuries and regeneration, especially in challenging injuries such as volumetric muscle loss, which also require vascular repair.

In this study, we aimed to develop new Lipo-niosomes based nanoparticles loaded with Amphotericin B(AmB) and Thymus Essential Oil (TEO) and test their effectiveness in the treatment of fungal-infected human adipose stem cells (hASCs).

In this experimental study, optimal formulation of AmB and TEO loaded lipo-niosome (based on lipid-surfactant thin-film hydration method) was chemically, and biologically characterized. Therefore, encapsulation capacity, drug release, size, and the survival rate of cells with different concentrations of free and encapsulated AmB/ TEO were evaluated using the MTT method, and its antifungal activity was compared with conventional AmB.

Lipo-Niosome containing Tween 60 surfactant: cholesterol: Dipalmitoyl phosphatidylcholine (DPPC): Polyethylene glycol (PEG) with a ratio of 20:40:60:3 were chosen as optimal formulation. Lipo-Niosomes entrapment efficiency was %94.15. The drug release rate after 24 hours was %52, %54, and %48 for Lipo-AmB, Lipo-TEO, and Lipo-AmB/TEO, respectively. Physical and chemical characteristics of the Lipo-Niosomes particles indicated size of 200 nm and a dispersion index of 0.32 with a Zeta potential of -24.56 mv. Furthermore, no chemical interaction between drugs and nano-carriers was observed. The cell viability of adipose mesenchymal stem cells exposed to 50 μg/ml of free AmB, free TEO, and free AmB/TEO was %13.4, %58, and %36.9, respectively. Whereas the toxicity of the encapsulated formulas of these drugs was %48.9, %70.8, and %58.3 respectively. The toxicity of nanoparticles was very low (%8.5) at this concentration. Fluorescence microscopic images showed that the antifungal activity of Lipo- AmB/TEO was significantly higher than free formulas of AmB, TEO, and AmB/TEO.

In this study, we investigated the efficacy of the TEO/AmB combination, in both free and encapsulatedniosomal form, on the growth of fungal infected-hASCs. The results showed that the AmB/TEO-loaded Lipo-Niosomes can be suggested as a new efficient anti-fungal nano-system for patients treated with hASCs.

Multiple sclerosis (MS) is a complex multifactorial neuro-inflammatory disorder. This complexity arises from the evidence suggesting that MS is developed by interacting with environmental and genetic factors. This study aimed to evaluate the miR-106a, miR-125b, and miR330- expression levels in relapsing-remitting multiple sclerosis (RRMS) patients. The miRNAs' impact on TNFSF4 and Sp1 genes through the NF-кB/TNF-α signaling pathway was analyzed by measuring the expression levels in case and controls.

In this in silico-experimental study, we evaluated the association of miR-106a, miR- 125b, and miR330- with TNFSF4 and SP1 gene expression levels in 60 RRMS patients and 30 healthy controls by real-time polymerase chain reaction (PCR).

The expression levels of miR-330, miR-106a, and miR125-b in blood samples of RRMS patients were predominantly reduced. The expression of TNFSF4 in patients demonstrated a significant enhancement, in contrast to the diminishing Sp1 gene expression level in controls.

Our findings indicated an association between miR-106a and miR-330 and miR125-b expression and RRMS in our study population. Our data suggested that the miR106-a, miR125-b, and mir330- expression are correlated with TNFSF4 and Sp1 gene expression levels.

Transforming growth factor-beta (TGF-β) superfamily and its members that include bone morphogenetic protein 15 (BMP15), anti-Mullerian hormone (AMH), growth /differentiation factor-9 (GDF9), and their respective receptors: BMPR1A, BMPR1B, and BMPR2 have been implicated as key regulators in various aspects of ovarian function. The abnormal function of the ovaries is one of the main contributing factors to polycystic ovarian syndrome (PCOS), so this study aimed to investigate the mRNA expression profile of these factors in granulosa (GCs) and cumulus cells (CCs) of those patients.

The case-control research was conducted on 30 women (15 infertile PCOS and 15 normo-ovulatory patients, 22≤age ≤38 years old) who underwent ovarian stimulation for in vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI) cycle. GCs/CCs were obtained during ovarian puncture. The expression analysis of the aforementioned genes was quantified using real-time polymerase chain reaction (PCR).

AMH and BMPR1A expression levels were significantly increased in GCs of PCOS compared to the control group. In contrast, GDF9, BMP15, BMPR1B, and BMPR2 expressions were decreased. PCOS' CC showed the same expression patterns. GDF9 and AMH were effectively expressed in normal CCs, and BMP15 and BMPR1B in normal GCs (P<0.05).

Differential gene expression levels of AMH and its regulatory factors and their primary receptors were detected in granulosa and cumulus cells in PCOS women. Since the same antagonist protocol for ovarian stimulation was used in both PCOS and control groups, the results were independent of the protocols. This diversity in gene expression pattern may contribute to downstream pathways alteration of these genes, which are involved in oocyte competence and maturation.

The main goal was to evaluate the effects of alginate on human sperm parameters during cryopreservation.

In this prospective study, twenty-five normozoospermic samples were divided into two groups,encapsulated with 1% alginate and the control group. The samples were then frozen by rapid freezing. Different sperm parameters including motility, normal morphology, viability, acrosome reaction, and DNA integrity, were examined before freezing and after thawing.

All sperm parameters had a significant decrease after thawing compared to before freezing. Our data showed a significant decrease in sperm motility of the alginate group but sperm viability, normal morphology, and DNA fragmentation were similar between the two groups. However, the rates of intact acrosome and native DNA were significantly lower in the control group compared to the alginate group (45.12 ± 11.1 vs. 55.25 ± 10.69 and 52.2 ± 11.92vs. 68.12 ± 10.15, respectively, P<0.05).

It seems that alginate can prevent premature acrosome reaction and protect sperm DNA from denaturation during the rapid freezing process.

There are a lot of data about the correlation of SARS-CoV-2 infection and hypertension (HTN), but most of themare in the increased risk of morbidity and mortality in patients with HTN. SARS-CoV-2 can interfere with host cellsthrough the renin-angiotensin system (RAS) via the angiotensin-converting enzyme 2 (ACE2) receptor. RAS activationis associated with pro-inflammatory effects through the ACE/Ang II/ Angiotensin II type 1 receptor (AT1R) pathwayor anti-inflammatory effects through ACE2/Ang1-7/Mas axis. In the current paper, we discuss the pathophysiology ofnewly diagnosed HTN and its effect on morbidity in patients with coronavirus disease 2019 (COVID-19).