nasser aghdami

Kienböck disease is a rare condition characterized by severe pain and restricted wrist movement. Variouspalliative methods have been proposed as therapeutic strategies for alleviating symptoms. Mesenchymal stromal cell transplantationhas been suggested as an innovative and promising approach due to its potential for inducing regeneration andimmunomodulation in the necrotic tissue. This study aims to evaluate the safety of autologous bone marrow derivedmesenchymal stromal cells (BM-MSCs) transplantation after core decompression in Kienböck disease. In this phase I of an open-label clinical trial, three patients (one female and two males) withstage 2 Kienböck disease underwent autologous BM-MSCs transplantation following lunate core decompression. Thepatients were followed up for six months to assess safety as well as secondary clinical outcomes, including pain level,range of motion (ROM), and functional disability. Safety of BM-MSCs injection following the core decompression was evaluated by recording post-treatmentcomplications during the six-month follow-up. No adverse events (AEs) or severe AEs (SAEs) were reported, indicatingthat BM-MSCs injection after core decompression is a safe intervention. All patients showed a remarkable reductionin visual analog scale (VAS) scores and "Disabilities of the Arm, Shoulder, and Hand" (DASH) questionnaire scores,suggesting the therapeutic potential of this intervention. Moreover, an increase in the ROM indicated that BM-MSCstransplantation can improve wrist functionality. Additionally, radiographic assessments before and after cell infusiondemonstrated a reduction in lunate sclerosis after six months of follow-up. The transplantation of autologous BM-MSCs following lunate core decompression seems to be a safeclinical intervention and may lead to pain relief in patients with Kienböck disease. Furthermore, this procedure may helpprevent disease progression during the follow-up period (registration number: NCT02646007).

Hematopoietic stem cell transplantation (HSCT) is a life-saving therapy for various hematologic disorders. Due to the bone marrow suppression and its long recovery period, secondary infections, like cytomegalovirus (CMV), Epstein-Bar virus (EBV), and adenovirus (AdV), are the leading causes of morbidity and mortality in HSCT cases. Drug resistance to the antiviral pharmacotherapies makes researchers develop adoptive T cell therapies like virus-specific T cell therapy. These studies have faced major challenges such as finding the most effective T cell expansion methods, isolating the expected subtype, defining the functionality of the end-cell population, product quality control, and clinical complications after the injection. This review discusses the viral infections after HSCT, T cells characteristics during chronic viral infection, application of virus-specific T cells (VSTs) for refractory infections, standard methods for producing VSTs and their limitation, clinical experiences on VSTs, focusing on outcomes and side effects that can be helpful in decision-making for patients and further researches.

Mesenchymal stromal cells (MSCs) play immunomodulatory role in various autoimmune diseases. Previouspre-clinical and clinical studies have shown that MSCs could be a therapeutic modality for psoriasis. However, themechanisms of treatment and its possible side effects are under investigation. In this study, the safety and probableefficacy of injecting allogeneic adipose-derived mesenchymal stromal cells (ADSCs) in psoriatic patients were evaluated. In this phase I clinical study with six months of follow-up, total number of 1×106 or 3×106cells/cm2 of ADSCs were injected into the subcutaneous tissue of each plaque as a single dose in three males and twofemales (3M/2F) with a mean age of 32.8 ± 8.18. The primary outcome was safety. Changes in clinical and histologicalindexes, the number of B and T lymphocytes in local and peripheral blood, and serum levels of inflammatory cytokineswere assessed. Paired t test was used to compare variables at two time points (baseline and six months after injection)and repeated measures ANOVA test was utilized for variables at three time points in follow-up visits. No major adverse effects such as burning, pain, itching, or any systemic side effects were observed followingADSCs injection, and the lesions showed slight to considerable improvement after injection. The mRNA expressionlevels of pro-inflammatory factors were reduced in the dermis of the patients after injection. The increased expressionlevel of Foxp3 transcription factor in the patient blood samples suggested modulation of inflammation after ADMSCsadministration. Six months after the intervention, no major side effects were reported, but skin thickness, erythema, andscaling of the plaques, as well as the PASI score, were decreased in majority of patients. Our study suggested that ADSC injection could be considered as a safe and effective therapeuticapproach for psoriatic plaques (registration number: IRCT20080728001031N24).

During chronic infections, a distinct physiological condition named “exhaustion” arises that is associated with the dysfunctionality in immune cells and their eventual removal from the environment, which evidently help the progress of infection or tumors in human or animal bodies. This state of immune cells could be under the control of different elements such as the antigen load, help from inhibitory cells, lack of costimulatory signals and etc. Exhaustion that has been found in different immune system cells, is usually accompanied by impaired effector function and proliferation of immune cells, poor memory recall, upregulation of inhibitory molecules, compromised metabolism and altered transcription program, and is considered a reversible process, unlike other physiological states like anergy or senescence, organized through the blockage of several factors. Although the emergence of these cells in viral infections and cancer is an undesirable event, the importance of the presence of exhausted cells in autoimmune diseases and organ transplantation is highlighted as a positive change. In this review, we aimed to determine the occurrence of this process in different immune cells, the characteristics obtained by these cells, effective and primitive factors on exhaustion, metabolic and transcriptional cell changes, and the use of these cells in autoimmune diseases and organ transplantation.

We conducted this study to determine the safety and evidence of effectiveness of SeptimebTM among patients with COVID-19.

An uncontrolled phase II clinical trial with SeptimebTM was implemented in Imam Khomeini Hospital as a before-and-after trial during May to October 2020. Considering the inclusion and exclusion criteria, 33 patients with COVID-19 were treated using SeptimebTM. The patients received the anti-inflammatory drug 150 mg /10 ml /IV infusion SeptimebTM on the first day and then 300 mg /20 ml / IV infusion from the second day onwards for at least 2 days and up to 13 days based on the improvement of clinical symptoms and laboratory findings in addition to treatment which were selected according to the national protocol. The patients were then evaluated for the treatment efficacy and side effects. Adherence to treatment, clinical observations, and side effects were recorded before and after the treatment.

The herbal drug SeptimebTM was injected in phase two of an uncontrolled clinical trial on 33 patients with COVID-19 in Imam Khomeini Hospital in Tehran as a before-and-after trial. The number of new cases admitted to the Intensive Care Unit (ICU) and the new need to Non-Invasive Ventilation (NIV) ecreased compared to before the treatment. Also, blood oxygen saturation and platelet count increased. Conversely, CRP, ESR, and ferritin levels decreased (p<0.05). Besides, SeptimebTM did not show any serious side effects except recurrent thrombophlebitis during the treatment.

We found some evidence regarding the efficacy of this drug and its low amount of short term side effects. The investigators recommend conducting the third phase of the clinical trial.

In late December 2019, a sudden severe respiratory illness of unknown origin was reported in China. In early January 2020, the cause of COVID-19 infection was announced a new coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Examination of the SARS-CoV-2 genome sequence revealed a close resemblance to the previously reported SARS-CoV and coronavirus Middle East respiratory syndrome (MERS-CoV). However, initial testing of drugs used against SARS-CoV and MERS-CoV has been ineffective in controlling SARS-CoV-2. One of the key strategies to fight the virus is to look at how the immune system works against the virus, which has led to a better understanding of the disease and the development of new therapies and vaccine designs.

This review discussed the innate and acquired immune system responses and how immune cells function against the virus to shed light on the human body's defense strategies.

Although immune responses have been revealed critical to eradicating infections caused by coronaviruses, dysregulated immune responses can lead to immune pathologies thoroughly investigated. Also, the benefit of mesenchymal stem cells, NK cells, Treg cells, specific T cells, and platelet lysates have been submitted as promising solutions to prevent the effects of infection in patients with COVID-19.

It has been concluded that none of the above has undoubtedly been approved for the treatment or prevention of COVID-19, but clinical trials are underway better to understand the efficacy and safety of these cellular therapies.

Pneumothorax following right-sided bacterial endocarditis is an infrequent medical complication usually reported in cases with a history of intravenous drug abuse. The following report describes the condition of a girl without congenital heart disease or a history of intravenous drug abuse who developed pneumothorax secondary to endocarditis.

Autologous transplantation of epidermal cells has been used increasingly to treat vitiligo patients and is a simple, safe, and relatively efficient method. However, the outcome is not always satisfactory, and some patients show less or no response to this treatment. This study was evaluated to identify genes expressed differently among responders and non-responders to cell transplantation to find potential markers that could predict 'patients' responses to this type of cell therapy. Eleven stable vitiligo patients who received autologous epidermal cell transplantation were included in this clinical trial study. Before cell transplantation, skin samples were obtained from the recipient’s vitiligo lesions. After epidermal cell transplantation, patients were followed for at least six months to assess the response to epidermal cell injection. RNA sequencing was used to determine potential gene expression profile differences between responder and non-responder vitiligo patients. The RNA sequencing results showed differences in expression levels of 470 genes between the skin specimens of responder versus non-responder patients. There were 269 up-regulated genes and 201 down-regulatedgenes. Upregulated genes were involved in processes, such as Fatty Acid Omega Oxidation. Down-regulated geneswere related to PPAR signaling pathway, and estrogen signaling pathway. Among the most differentially expressed genes (DEGs) with the most altered RNA expression levels in responders versus non-responder patients, we selected three genes (up-regulated genes KRTAP10-11 and down-regulated genes IP6K2 and C9) as potential biomarkers, which are involved in associated pathways. Based on our findings, it is estimated that proposed genes might predict the response of vitiligo patients to cell therapy. However, further studies are required to clarify the role of these genes in pathogenesis and to characterize gene expression in a larger number of vitiligo patients in the context of epidermal cell transplantation therapy (registration number: IRCT201508201031N16).

Different Cell Culture medias can affect the expansion of T cells. The aim of this study is to assess signaling pathways, protein interactions and genes in T cells cultured in different common T cell expansion medias to select the best candidate.

In this in silico observational study, with the use of bioinformatics analysis and the use of enrichment databases, gene expression profiles were investigated using microarray analysis.

The results of this study were the joint selection of 26 upregulated genes and 59 downregulated genes that were involved in SREBP control of lipid synthesis, co-stimulatory signal during T-cell activation mitosis and chromosome dynamics, telomeres, telomerase, and cellular aging signal pathways.

Using bioinformatics analyzes, integrated and regular genes were selected as common genes CD80, LST1, ATM and ITM2B 4-1BBL, Akt inhibitor, interleukin 7 and 15 expansion media.

Perianal fistulas in Crohn’s disease (CD) are the main challenges in inflammatory bowel diseases (IBDs). Some of the fistulas are refractory to any therapeutic strategy. The aim of this study was to evaluate the therapeutic effects of mesenchymal stromal cells (MSCs) as a novel promising modality for the treatment of fistulizing CD.

Materials And Methods:

This case series clinical interventional study was conducted from 2014 to 2017 at Shariati Hospital, an IBD referral center in Tehran, Iran. Refractory adult patients with CD who had draining perianal fistulas were enrolled in this study. All patients were examined by a colorectal surgeon and the fistula imaging studies were performed by pelvic magnetic resonance imaging (MRI). After autologous bone marrow (BM) aspiration and MSCs isolation, the cells were cultured and passaged under current good manufacturing practice (cGMP) conditions. Four intra-fistula injections of cells, each containing 40×106 MSCs suspended in fibrin glue, were administered by an expert surgeon every 4 weeks. Procedure safety, feasibility and closure of the perianal fistulas at week 24 were assessed. Clinical examination and MRI findings were considered as the primary end points.

In total, 5 patients (2 males and 3 females) were enrolled in this study. No adverse events were observed during the six-month follow-up in these patients. Both the Crohn’s Disease Activity Index (CDAI) and Perianal Disease Activity Index (PDAI) scores decreased in all patients after cell injections and one patient achieved complete remission with closure of fistulas, discontinuation of fistula discharge, and closure of the external opening.

Local injection of MSCs combined with fibrin glue is potentially a safe and effective therapeutic approach for complex perianal fistulas in patients with CD.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with very limited treatment options. Stem cells have been raised as a new treatment modality for these patients. We have designed a single-center, prospective, open-label, and single arm clinical trial to assess the safety, feasibility, and rather efficacy of administrating allogeneic adipose-derived mesenchymal stromal cells (Ad-MSCs) in ALS patients. We enrolled 17 patients with confirmed ALS diagnosis with ALS Functional Rating Scale-Revised (ALSFRS-R) ≥24 and predicted forced vital capacity (FVC) ≥40%. Allogeneic Ad-MSCs were transplanted intravenously for all patients. Follow-ups were done at 24 hours, 2, 4, 6, and 12 months after cell infusion by checking adverse events, laboratory tests, and clinically by ALSFRS-R and FVC. Patients were also followed five years later and ALSFRS-R score was recorded in the survived individuals. There was no report of severe adverse events related to cell infusion. Two patients experienced dyspnea and chest pain 36 and 65 days after cell infusion due to pulmonary emboli. The progressive decrease in ALSFRS-R and FVC levels was recorded and three patients died in the first year. During five years follow up, despite a notable decrease in functional scores, 5 patients survived. Intravenous (IV) infusion of allogeneic Ad-MSCs in ALS patients is safe and feasible. The survival rate of the patients is more than IV autologous MSCs (Registration number: IRCT20080728001031N26).

Hair loss is a prevalent medical problem in both men and women. Maintaining the hair inductivity potential of human dermal papilla cells (hDPCs) during cell culture is the main issue in hair follicle morphogenesis and regeneration. The present study was conducted to compare the effects of different concentrations of exosomes derived from human adipose stem cells (hASCs) and platelet-rich plasma (PRP) on the proliferation, migration and expression of alkaline pholphatase (ALP), versican, and smooth muscle alpha-actin (α-SMA) in human DPCs.

In this experimental study, hDPCs, human hair DPCs and outer root sheet cells (ORSCs) were separated from healthy hair samples. The protocol of exosome isolation from PRP and hASCs comprises serial low speed centrifugation and ultracentrifugation. The effects of different concentrations of exosomes (25, 50, 100 μg/ ml) derived from hASCs and PRP on proliferation (MTS assay), migration (scratch test) and expression of ALP, versican and α-SMA (real time-polymerase chain reaction) in human DPCs were evaluated.

The flow cytometry analysis of specific cytoplasmic markers showed expression of versican (77%) and α-SMA (60.8%) in DPCs and K15 (73.2%) in ORSCs. According to NanoSight Dynamic Light Scattering, we found the majority of ASCs and PRP-exosomes (ASC-Exo and PRP-Exo) to be 30-150 nm in size. For 100 μg/ml of ASCs-Exo, the expressions of ALP, versican and α-SMA proteins increased by a factor of 1.2, 2 and 3, respectively, compared to the control group. The findings of our experiments illustrated that 100 μg/ml of ASCs-Exo compared to the same concentration of PRP-Exo significantly promote DPC proliferation and migration in culture.

This study introduced the potential positive effect of ASC-Exo in increasing the proliferation and survival of DPCs, while maintaining their hair inductivity. Thus, ASCs-Exo possibly provide a new effective procedure for treatment of hair loss.

Systemic sclerosis (SSc) is a connective tissue disease associated with vascular damage and multi organ fibrotic changes with unknown pathogenesis. Most SSc patients suffer from defective angiogenesis/vasculogenesis and cardiac conditions leading to high mortality rates. We aimed to investigate the cardiovascular phenotype of SSc by cardiogenic differentiation of SSc induced pluripotent stem cells (iPSC).

In this experimental study, we generated iPSC from two diffuse SSc patients, followed by successful differentiation into endothelial cells (ECs) and cardiomyocytes (CMs).

SSc-derived EC (SSc-EC) expressed KDR, a nearly EC marker, similar to healthy control-EC (C1-EC). After sorting and culturing KDR+ cells, the resulting EC expressed CD31, a late endothelial marker, but vascular endothelial (VE)-cadherin expression markedly dropped resulting in a functional defect as reflected in tube formation failure of SSc-EC. Interestingly, upregulation of SNAI1 (snail family transcriptional repressor 1) was observed in SSc-EC which might underlie VE-cadherin downregulation. Furthermore, SSc-derived CM (SSc-CM) successfully expressed cardiacspecific markers including ion channels, resulting in normal physiological behavior and responsiveness to cardioactive drugs.

This study provides an insight into impaired angiogenesis observed in SSc patients by evaluating in vitro cardiovascular differentiation of SSc iPSC.

The direct approach of cardiac tissue engineering is to mimic the natural tissue of heart, considering the significant role of scaffolding and mechanical simulation. 

To achieve this purpose, a composite Polycaprolactone (PCL)/Gelatin electrospun scaffold with a ratio of 70:30 and with the most similarities to the cardiac extracellular matrix was fabricated with aligned nanofibers. The scaffold was evaluated using scanning electron microscopy (SEM), mechanical strength analysis, and contact angle test. To simulate the cardiac contraction, a developed Mechanical Loading Device (Bioreactor) was designed to apply a mechanical load with a specific frequency and tensile rate values in the direction of aligned nanofibers due to simulating natural cardiac tissue.

Based on our results from the contact angle and mechanical strength tests, we concluded that our designed scaffold has appropriate adhesion and strength to use as cardiac scaffold and is suitable for imposing the frequency of 1Hz and 10% strain. The Bioreactor also worked properly in producing the required frequency, tensile rate and temperature. 

Since an essential difference between cardiomyocytes and other cells is their contraction, manufacturing a biomimetic bioreactor to simulate the normal cardiac contraction of cardiomyocytes and their required temperature to be survived in-vitro could be a promising approach in cardiac tissue engineering.

Functional cardiac tissue engineering holds promise as a candidate approach for myocardial infarction. Tissue engineering has emerged to generate functional tissue constructs and provide an alternative means to repair and regenerate damaged heart tissues.

In this experimental study, we fabricated a composite polycaprolactone (PCL)/gelatine electrospun scaffold with aligned nanofibres. The electrospinning parameters and optimum proportion of the PCL/ gelatine were tested to design a scaffold with aligned and homogenized nanofibres. Using scanning electron microscopy (SEM) and mechanophysical testes, the PCL/gelatine composite scaffold with a ratio of 70:30 was selected. In order to simulate cardiac contraction, a developed mechanical loading device (MLD) was used to apply a mechanical stress with specific frequency and tensile rate to cardiac progenitor cells (CPCs) in the direction of the aligned nanofibres. Cell metabolic determination of CPCs was performed using real-time polymerase chain reaction(RT-PCR).

Physicochemical and mechanical characterization showed that the PCL/gelatine composite scaffold with a ratio of 70:30 was the best sample. In vitro analysis showed that the scaffold supported active metabolism and proliferation of CPCs, and the generation of uniform cellular constructs after five days. Real-time PCR analysis revealed elevated expressions of the specific genes for synchronizing beating cells (MYH-6, TTN and CX-43) on the dynamic scaffolds compared to the control sample with a static culture system.

Our study provides a robust platform for generation of synchronized beating cells on a nanofibre patch that can be used in cardiac tissue engineering applications in the near future.

In the present study, we examined the tolerance-inducing effects of human adipose-derived mesenchymal stem cells (hAD-MSCs) and bone marrow-derived MSCs (hBM-MSCs) on a nonhuman primate model of skin transplantation.

In this experimental study, allogenic and xenogeneic of immunomodulatory properties of human AD-MSCs and BM-MSCs were evaluated by mixed lymphocyte reaction (MLR) assays. Human MSCs were obtained from BM or AD tissues (from individuals of either sex with an age range of 35 to 65 years) and intravenously injected (2×106 MSCs/kg) after allogeneic skin grafting in a nonhuman primate model. The skin sections were evaluated by H&E staining for histopathological evaluations, particularly inflammation and rejection reaction of grafts after 96 hours of cell injection. At the mRNA and protein levels, cellular mediators of inflammation, such as CD4+IL-17+ (T helper 17; Th17) and CD4+INF-γ+ (T helper 1, Th1) cells, along with CD4+FoxP3+ cells (Treg), as the mediators of immunomodulation, were measured by RT-PCR and flow cytometry analyses.

A significant Treg cells expansion was observed in MSCs-treated animals which reached the zenith at 24 hours and remained at a high concentration for 96 hours; however, Th1 and Th17 cells were significantly decreased. Our results showed that human MSCs significantly decrease Th1 and Th17 cell proliferation by decreasing interleukin-17 (IL-17) and interferon-γ (INF-γ) production and significantly increase Treg cell proliferation by increasing FoxP3 production. They also extend the allogenic skin graft survival in nonhuman primates. Histological evaluations showed no obvious presence of inflammatory cells or skin redness or even bulging after MSCs injection up to 96 hours, compared to the group without MSCs. There were no significant differences between hBM-MSCs and hAD-MSCs in terms of histopathological scores and inflammatory responses (P<0.05).

It seems that MSCs could be regarded as a valuable immunomodulatory tool to reduce the use of immunosuppressive agents.

This clinical study evaluated the effect of autologous muscle-derived cell (MDC) injection for the treatment of female patients with pure stress urinary incontinence (SUI).

A total of 20 women with SUI received transurethral injections of autologous MDCs. Baseline and follow-up evaluations consisted of physical examinations (cough stress tests), one-hour pad test, Incontinence Impact Questionnaire-7 (IIQ-7), and Urogenital Distress Inventory (UDI-6) scoring. The patients were followed one week as well as 1, 3, 6, 9, 12, and 24 month(s) after the procedure. Multichannel urodynamic study were performed before and 24 months after the intervention. The incidence and severity of adverse events (AE) were also recorded at each follow-up visit.

A total of 20 eligible female patients with the chief complaint of SUI that was unresponsive to conservative management, was enrolled in the trial, 17 of whom completed all follow-up visits. At 12th months, 10 (59%) patients had complete response, whereas 2 (12%) and 5 (29%) patients had partial and no response, respectively. At 24th months, relapse of SUI in 5 out of 10 complete responders (29%) and 2 out of 2 partial responders to the treatment, respectively. The intervention produced no serious AE during the trial.

According to our results, though obtained from a limited number of patients, MDC therapy was a minimally invasive and safe procedure for treatment of female patients with pure SUI. However, currently, the efficacy of this type of treatment for SUI is not sufficiently high and multi-center randomized clinical trials are required to be conducted before reaching a concrete conclusion.

Recently, the promising potential of fibroblast transplantation has become a novel modality for skin rejuvenation. We investigated the long-term safety and efficacy of autologous fibroblast transplantation for participants with mild to severe facial contour deformities.

In this open-label, single-arm phase IIa clinical trial, a total of 57 participants with wrinkles (n=37, 132 treatment sites) or acne scars (n=20, 36 treatment sites) who had an evaluator’s assessment score of at least 2 out 7 (based on a standard photo-guide scoring) received 3 injections of autologous cultured fibroblasts administered at 4-6 week intervals. Efficacy evaluations were performed at 2, 6, 12, and 24 months after the final injection based on evaluator and patient’s assessment scores.

Our study showed a mean improvement of 2 scores in the wrinkle and acne scar treatment sites. At sixth months after transplantation, 90.1% of the wrinkle sites and 86.1% of the acne scar sites showed at least a one grade improvement on evaluator assessments. We also observed at least a 2-grade improvement in 56.1% of the wrinkle sites and 63.9% of the acne scar sites. A total of 70.5% of wrinkle sites and 72.2% of acne scar sites were scored as good or excellent on patient assessments. The efficacy outcomes remained stable up to 24-month. We did not observe any serious adverse events during the study.

These results have shown that autologous fibroblast transplantation could be a promising remodeling modality with long-term corrective ability and minimal adverse events (Registration Number: NCT01115634).

Re-epithelialization has an important role in skin wound healing. Delays in re-epithelialization are more likely to create the chronic wound. Impaired wound healing leads to a large burden of morbidity and mortality. Current treatments based on the use of autografts, allografts and xenografts, suffer from limitations such as, quantity of donor skin available, donor-site infection, potential risk of disease transmission and rejection of the graft. Given this problems, nanomaterial such as copper nanoparticles has attracted considerable research interest because of their high surface area to volume ratio, high stability, clinical safety, and antibacterial effects. Epithelialization involves keratinocyte migration and proliferation to the wound site. Therefore, this study was conducted to investigate the effect of copper nanoparticles on keratinocyte cell migration and proliferation. This experimental study was performed in Royan Institute, Tehran in 2016. In this study we investigated the effect of copper nanoparticles on viability, migration and proliferation of keratinocyte cells. Cultured human foreskin Keratinocyte cells were exposed to various concentration (1, 10 and 100 µmol) and sizes (40 and 80 nm) of copper nanoparticles for 24, 48 and 72 hours. The copper nanoparticles toxicity was examined by MTS assay. Cell migration has also been investigated with the Scratch assay. The results showed that the 1, 10 and 100 µmol concentrations of 40 and 80 nm copper nanoparticles were not toxic for cultured human foreskin keratinocyte cells after 24h. It was also found keratinocyte cell proliferation was increased by 1 µmol concentration of 80 nm copper nanoparticles after 72h. The results of the Scratch assay showed that the 1 µmol concentration of 80 nm copper nanoparticles significantly (P<0.05) increased keratinocyte cell migration compared to deionized water as of control group after 24h. It seems the 1 µmol concentration of 80 nm copper nanoparticle could stimulate keratinocyte cell migration and proliferation. However, in vivo studies conducted on animal model wound healing subjects are needed for determining re-epithelialization.

Using mesenchymal stem cells (MSCs) is regarded as a new therapeutic approach for improving fibrotic diseases. the aim of this study to evaluate the feasibility and safety of systemic infusion of autologous adipose tissue-derived MSCs (AD-MSCs) in peritoneal dialysis (PD) patients with expected peritoneal fibrosis.
This study was a prospective, open-label, non-randomized, placebo-free, phase I clinical trial. Case group consisted of nine eligible renal failure patients with more than two years of history of being on PD. Autologous AD-MSCs were obtained through lipoaspiration and expanded under good manufacturing practice conditions. Patients received 1.2 ± 0.1×106 cell/kg of AD-MSCs via cubital vein and then were followed for six months at time points of baseline, and then 3 weeks, 6 weeks, 12 weeks, 16 weeks and 24 weeks after infusion. Clinical, biochemical and peritoneal equilibration test (PET) were performed to assess the safety and probable change in peritoneal solute transport parameters.
No serious adverse events and no catheter-related complications were found in the participants. 14 minor reported adverse events were self-limited or subsided after supportive treatment. One patient developed an episode of peritonitis and another patient experienced exit site infection, which did not appear to be related to the procedure. A significant decrease in the rate of solute transport across peritoneal membrane was detected by PET (D/P cr=0.77 vs. 0.73, P=0.02).
This study, for the first time, showed the feasibility and safety of AD-MSCs in PD patients and the potentials for positive changes in solute transport. Further studies with larger samples, longer follow-up, and randomized blind control groups to elucidate the most effective route, frequency and dose of MSCs administration, are necessary (Registration Number: IRCT2015052415841N2).

Cardiovascular progenitor cells (CPCs) are introduced as one of the promising cell sources for preclinical studies and regenerative medicine. One of the earliest type of CPCs is cardiogenic mesoderm cells (CMCs), which have the capability to generate all types of cardiac lineage derivatives. In order to benefit from CMCs, development of an efficient culture strategy is required. We aim to explore an optimized culture condition that uses human embryonic stem cell (hESC)-derived CMCs.
In this experimental study, hESCs were expanded and induced toward cardiac lineage in a suspension culture. Mesoderm posterior 1-positive (MESP1) CMCs were subjected to four different culture conditions: i. Suspension culture of CMC spheroids, ii. Adherent culture of CMC spheroids, iii. Adherent culture of single CMCs using gelatin, and iv. Adherent culture of single CMCs using Matrigel.
Although, we observed no substantial changes in the percentage of MESP1 cells in different culture conditions, there were significantly higher viability and total cell numbers in CMCs cultured on Matrigel (condition iv) compared to the other groups. CMCs cultivated on Matrigel maintained their progenitor cell signature, which included the tendency for cardiogenic differentiation.
These results showed the efficacy of an adherent culture on Matrigel for hESC-derived CMCs, which would facilitate their use for future applications.

Amyotrophic lateral sclerosis (ALS) is the most severe disorder within the spectrum of motor neuron diseases (MND) that has no effective treatment and a progressively fatal outcome. We have conducted two clinical trials to assess the safety and feasibility of intravenous (IV) and intrathecal (IT) injections of bone marrow derived mesenchymal stromal cells (BM-MSCs) in patients with ALS.
This is an interventional/experimental study. We enrolled 14 patients that met the following inclusion criteria: definitive diagnosis of sporadic ALS, ALS Functional Rating Scale (ALS-FRS) ≥24, and ≥40% predicted forced vital capacity (FVC). All patients underwent bone marrow (BM) aspiration to obtain an adequate sample for cell isolation and culture. Patients in group 1 (n=6) received an IV and patients in group 2 (n=8) received an IT injection of the cell suspension. All patients in both groups were followed at 24 hours and 2, 4, 6, and 12 months after the injection with ALS-FRS, FVC, laboratory tests, check list of side effects and brain/spinal cord magnetic resonance imaging (MRI). In each group, one patient was lost to follow up one month after cell injection and one patient from IV group died due to severe respiratory insufficiency and infection.
During the follow up there were no reports of adverse events in terms of clinical and laboratory assessments. In MRI, there was not any new abnormal finding. The ALS-FRS score and FVC percentage significantly reduced in all patients from both groups.
This study has shown that IV and IT transplantation of BM-derived stromal cells is safe and feasible (Registration numbers: NCT01759797 and NCT01771640).

To evaluate the effect of bone marrow-derived mononuclear cells (BM-MNCs) on clinical outcome and cardiac function in chronic heart failure (HF).
An uncontrolled, open-label trial was performed on symptomatic patients (New York Heart Association [NYHA] Functional Classification II–IV) receiving maximal medical therapy for at least 2 months, with a left ventricular (LV) ejection fraction We enrolled 58 patients in our study. There was a significant improvement to exercise and functional capacity (evaluated by NYHA classification and 6-min walking distance) with both groups (for all P It seems that intracoronary infusion of bone marrow-derived mononuclear stem cells is a safe treatment for patients with advanced HF and further studies need to address the best type of cell, route of administration, and criteria for patient selection.