cell

Stem cell treatments depend not only on the type of cell to be used but also on the different implantation techniques. Intravascular cell injections are known to rapidly separate from the vessels. On the other hand, it is also well known that direct injection into the myocardium provides better coupling within the heart muscle. That were the cases of Embriofetal stem cell (HFDSC) or Autologous stem cells (ABMSC) in our experience focused on direct approaches.

Between 2003 and 2011, 17 patients with heart failure were treated with stem cells as part of our Foundation’s Regenerative Medicine program. In several centers and countries 4 with ischemic cardiomyopathy of which 3 were surgically implanted with autologous bone marrow stem cells (ABMSC) plus bypass surgery. One patient was treated with hyperbaric medicine plus bypass surgery. Patients with idiopathic cardiomyopathy were implanted surgically with 2 different types of stem cells. Ten patients were implanted with stem cells derived from human fetuses (HFDSCs) and three patients with autologous bone marrow stem cells (ABMSC). The ejection fractions of the coronary artery bypass graft off pump OPCAB (control group) versus coronary artery bypass group off pump OPCAB plus stem cell transplantation were as followsin the entire serie: preoperative, 30.7% +/- 2.5% compared to 29.4% +/- 3.6%; 1 month, 36.4% +/- 2.6% versus 42.1% +/- 3.5%; 3 months, 36.5% +/- 3.0% vs. 45.5% +/- 2.2%; And 6 months, 37.2% +/- 3.4% versus 46.1% +/- 1.9% (p <0.001). The first patient performed at our center in Argentina in this series is alive and asymptomatic 15 years after implantation, and the rest of this series we do not have current data. A patient without visible vessels in the anterior wall of the left ventricle was treated with 18 hyperbaric chamber sections from one hour at 1.4 AT. After creating angiogenesis, the patient was operated on receiving 2 grafts (mammary and venous) without extracorporeal circulation in the anterior descending artery and diagonal artery. The preoperative ejection fraction was 33% at 90 months of follow up the ejection fraction was 58%. The patient at 90 months was asymptomatic. Of the idiopathic heart disease group, nine patients underwent median sternotomy, and received human fetal stem cells (HFDSCs from ectopic pregnancy or spontaneous abortion, three patients received autologous bone marrow stem cells ABMSC) and 1HFDSCs for Minimally Invasive Surgery. Patients with HFDSC, compared to baseline, improved: The mean (±SD) NYHA class decreased from 3.4 ± 0.5 to 1.33 ± 0.5 (P = 0.001); Mean EF increased 31%, from 26.6% ± 4.0% to 34.8% ± 7.2% (p = 0.005); the yield in ETT increased 291.3%, from 4.25 minutes to 16.63 minutes (128.9% in metabolic equivalents, 2.45 to 5.63) (P <0.0001); the mean LVEDD decreased 15%, from 6.85 ± 0.6cm to 5.80 ± 0.58cm (P <0.001); the mean performance on the 6-minute walk test increased 43.2%, from 251 ± 113.1 seconds to 360 ± 0 seconds (P = 0.01); the mean distance increased 64.4%, from 284.4 ± 144.9m to 468.2 ± 89.8m (P = 0.004); and the mean score in the Minnesota congestive HF test decreased from 71 ± 27.3 to 6 ± 5.9 (p <0.001). Kaplan-Maier’s probability of survival at 40 months was 66%. No rejection or cancer was observed at follow-up, in this series follow-up was discontinued at 4 years. In idiopathic patients receiving autologous cells by Mininvasive technique preoperative NYHA was 3.6 (+/- 0.70) 6 months after receiving stem cell therapy. The mean value of the functional class was 1.9 (+/- 0.90) (p <0.005). ) showing marked clinical improvement. The preimplantation ejection fraction was 28% (+/- 3.6%) and at 6 months 44% (+/- 4.7%) (p <0.005). There was a similar change in ventricular diameters: After 6 months LVESV went from 50mm (+/- 3.3) to 42mm (+/- 4.5) (p <0.05). Two of the three patients in this group received re-synchronization therapy; one died at 10 years and 4 months, another at age 11 and another one alive at 12 years of the implant. More experience should be performed with different techniques and cells to find the appropriate treatment in this type of patients.

Fluorescein was conjugated with 1-methyl-o-carborane and the resulting bioconjugate was biologically evaluated through microscopic and flow cytometric studies in pancreatic cancer and squamous cell carcinoma cell lines. The uniform distribution of this bioconjugate, as well as its moderate cytotoxicity and higher boron content relative to present boronated delivery agents sodium borocaptate (BSH) and boronophenylalanine (BPA), provide justification for its further evaluation as a potential delivery agent for BNCT.

To repair articular cartilage (AC) defects in osteoarthritic patients, one approach is to engineer three-dimensional grafts with physicochemical properties similar to endogenous AC. Such grafts can be grown in bioreactors that provide environmental conditions favoring chondrogenesis. Studies show mechanical stimulation during the culturing process greatly enhances development of functional engineered grafts. A review of literature on bioreactor options reveals a lack of capacity to simultaneously stimulate cells with a combination of shear stress and oscillating hydrostatic pressure, both of which are important parts of the in vivo AC environment. It is hypothesized that combining both forces in a new bioreactor design will contribute to better AC tissue growth. In this paper, we provide a brief review of bioreactors and describe a new computer-controlled perfusion and pressurized bioreactor system, and the novelty of its control programming features for service in a host of applications. We briefly summarize results on synergistic effects in employing perfusion, oscillating hydrostatic pressure in a scaffold free environment and with the addition of encapsulation for inducing chondrogenesis. We further describe efforts to modify the newly developed system to include a continuous flow and pressurized centrifugal mode to enhance further the capabilities for inclusion of very high shear stresses. Applications for several other cell and tissue engineering approaches are discussed. 

Background: Mesenchymal stem cell (MSC) effects can shift immune responses toward anti-inflammatory and tolerogenic phenotypes, potentially helping patients with bronchiolitis obliterans syndrome (BOS). Methods: We evaluated the effect of infusing allogeneic MSC intravenously in 9 patients with moderate BOS refractory to standard therapy who were not candidates for retransplant, dividing them into 3 dosing groups: Group 1, 1×106 MSC/kg (n=3); Group 2, 2×106 MSC/kg (n=3); and Group 3, 4×106 MSC/kg (n=3). We recorded pulmonary function tests, laboratory variables, and serum biomarkers pre- and post-MSC infusion. Results: These patients had significant decline in forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) over 1 year pre-MSC infusion (mean ± SD) FVC, 3.11±0.98 L, and FEV1 1.99+0.64 L versus FVC 2.58±1.03 and FEV1 1.61±0.52 just before infusion (P<0.05); representing a mean loss of 530 mL in FVC and 374 mL in FEV1 over 12 months. One year post-MSC infusion, mean FVC and FEV1 increased to 2.66±1.01 L and 1.63±0.55 L, respectively (changes no longer significant compared to before MSC infusion). Patients in Group 1 showed elevation of tolerance-inducing T regulatory cells and increased levels of epidermal growth factor. Tolerance-inducing Th-2 cytokines increased in Groups 1 and 2. These changes were not significantly different in these small sub-groups. Conclusion: MSC infusion appears to slow down or reverse the progressive decline in lung function in some patients with moderate BOS, possibly by inducing anti-inflammatory effects and promoting cell proliferation and angiogenesis.

One of the factors of assisted reproduction technology (ART) success is an adequate growth and development of endometrium. At the end of follicular phase of menstrual cycle endometrium reaches its greatest thickness. It is believed that there is a critical limit of endometrial thickness beyond which the implantation of embryo is unlikely or impossible [1-5]. In practice of ART programs ultrasound measurement of endometrial thickness is used to evaluate uterine lining growth. Scientific literature is debatable as to what thickness of endometrium should be considered optimal, some researchers emphasize the negative impact of “thin endometrium” on the success of ART programs [1-12], while others do not agree [6,7,9]. Nevertheless, when endometrial thickness in ART program does not exceed 6 mm the chance of pregnancy occurring is very low (Kumbak B, et al. 2009). 

Forebrain GABAergic neurons, the main inhibitory type of neuron in the cortex and hippocampus, represent a highly heterogeneous cell population that has been implicated in the predisposition to epilepsy and the onset of seizure. Earlier attempts to restore inhibition and reduce seizure in animal models of epilepsy have been carried out using embryonic basal forebrain tissue as source of immature GABAergic progenitors in cell-based therapies, with promising results. For therapeutic strategies this approach appears unrealistic, while the use of pluripotent stem cells to obtain immature GABAergic neurons opens new and promising avenues. Research on neural stem cells and pluripotent stem cells has greatly advanced and protocols have been established to efficiently direct progenitor cells to differentiate towards the GABAergic lineage. However, being highly heterogeneous, these neurons are difficult to be fully represented in vitro. Better knowledge on the expressed gene profiles, at single cell level, and the differentiation trajectory of these neurons will consent a more precise monitoring of the differentiation steps. Here we review the current literature about how to obtain and characterize genuine inhibitory neurons, how these can be grafted in animal models (and one day possibly in human) and which diseases could potentially be targeted and the efficiency of therapeutic outcome. The main obstacles that need to be overcome are: a) choice of an appropriate animal model, b) availability of human cells prone to GABA differentiation, c) the full representation of all IN subtypes, their proportions and their physiological activities, d) how to monitor them on the long-term after transplant.

Natural killer (NK) cells, the third population of lymphoid cells, comprise 5%-25% of peripheral blood (PB) lymphocytes and represent the first line of defense against infections and tumors [1-7]. They can be derived from: bone marrow, PB, cryopreserved umbilical cord blood (UCB), human embryonic stem cells (hESCs), induced pluripotent stem cells (iPSCs), and various cell lines such as NK-92 and KHYG-1 [1]. NK cells; which have been divided into cytotoxic, tolerant, and regulatory subsets; are classified into: (1) naïve CD56 bright CD 16 dim CD 3 dim cells, (2) mature CD56 dim CD16 bright CD3 dim cells, and (3) lymphoid tissue-resident CD69+/CXCR6+ NK cells [1,2,8-11]. Although NK cells have been traditionally considered as part of the innate immune system, they have recently been shown to exhibit many of the features associated with adaptive immunity [8,12]. The functions of NK cells which are influenced by several cytokines include: elimination of infected cells, destruction of cancer cells, reducing the incidence of graft versus host disease (GVHD) following hematopoietic stem cell transplantation (HSCT), and regulation of pregnancy outcome [10,11,13]. 

Mesenchymal stem cells (MSCs) conditioned medium (CM) has a promising prospect towards skin regeneration. Therefore, human dental pulp and adipose stem cells (DPSCs and ADSCs) were isolated, propagated and evaluated for their stemness and genetic stability over time in culture before making CM. We aimed to characterize the applicability of lyophilized ADSCs and DPSCs derived CM (AD-CM and DP-CM) at 5 mg, 10 mg and 20 mg for wound healing process. The ability of wound closure was assessed by direct human dermal fibroblast cell scratch assay, treated with variable concentrations of AD-CM and DP-CM in vitro. Additionally, we also assessed the expression of different cytokines and growth factors secreted from ADSCs and DPSCs in the CM relevant to the wound healing by cytokine array analysis. Our data demonstrates a significant effect of both the AD-CM and DP-CM in wound healing within 24 hrs compared to that in control.

Natural killer cells represent the first line of defense against infections and tumors and can be derived from various sources including: bone marrow, peripheral blood, specific types of human stem cells, and certain cell lines. The functions of natural killer cells are influenced by: several cytokines, activating and inhibitory receptors, as well as other immune cells such as dendritic cells and mesenchymal stem cells. Natural killer cells are attractive candidates for adoptive cellular therapy in patients with hematologic malignancies and solid tumors in addition to recipients of various forms of hematopoietic stem cell transplantation as they enhance antitumor effects without causing graft versus host disease. Several clinical trials have shown safety and efficacy of natural killer cell products obtained from autologous as well as allogeneic sources and used in conjunction with cytotoxic chemotherapy, monoclonal antibodies and novel agents. The following review, which includes extensive literature review on several aspects of natural killer cells, will give particular attention to: the rising role of natural killer cell therapies in patients with malignant hematological disorders, solid tumors and in recipients of stem cell therapies; preparation and manufacture of natural killer cell products; challenges facing the utilization of this form of cellular therapy including evolution of resistance; and maneuvers that can be employed to enhance the efficacy of natural killer cell therapies as well as suggested solutions to resolve the remaining challenges.

In recent years, stem cells technology have been used widely in basic and clinical science researches LIPUS (low-intensity pulsed ultrasound) is another technique commonly used in conjunction with stem cells that can have complications after applications. One of the important issues in using this modern technique is the occurrence of opportunistic infections and inflammatory reactions in the rejection or destruction of these cells and in turn making ineffective of its applications, which have been reviewed in the following.

ystemic sclerosis (SScl) is an autoimmune disorder of unknown aetiology, characterised by fibrosis and microvascular injury of the affected organs. The hallmark of the disease is thickening and tightness of the skin and the subcutaneous tissue. SScl can affect virtually any organ systems, most importantly the skin, blood vessels, lungs, kidneys, gastrointestinal tract, and the heart [1].

The pandemic of COVID-19 has adversely affected the world in many aspects. The health and economic sectors suffer most of the repercussions of this disease. The search for a cure for this rapidly spreading virus which is causing massive life losses worldwide requires clear understanding of the immunopathogenesis of this virus so as to develop pinpointed targeted therapies rather than relying mainly on supportive care measures and drug repurposing to fight this life-threatening virus infection. Neutrophils, neutrophil extracellular traps (NETs), and NETosis are not well studied not only in COVID-19, but also in coroviruses in general. The review will shed lights on the functions of neutrophils, NETs, and NETosis in various infectious complications as well as in sepsis and acute lung conditions in an attempt to understand their actual roles and in order to help in designing targeted therapies in the near future.

Infectious diseases are a leading cause of death worldwide [1,2]. The Mid-20th century witnessed most of the antimicrobial discoveries but recently there is dramatic shortage of new classes of antimicrobial agents due to failure to build a sustainable antimicrobial discovery platform [1-4]. For example, antibiotics comprise ˂ 1.5% of the compounds under investigation at the major pharmaceutical and biotechnology companies [1,5]. 

Objectives: The aim of this study was to assess the knowledge, attitude and motivation toward stem cell donation among Saudi population in Riyadh, Saudi Arabia. Methods: This is a cross-sectional study that was conducted at different malls in Riyadh. Selection of malls was done randomly according to the geographical distribution of Riyadh, in which sample size was calculated and distributed equally. The participants were asked to complete a questionnaire that addressed their knowledge, attitude and motivation toward stem cell transplantation and donation. Results: Results of this study showed that population knowledge about stem cell transplantation and donation is considered to be low. Only (37.8%) has enough information about stem cell transplantation and donation. There is a positive correlation between level of education and participant’s knowledge regarding stem cell transplantation and donation. The study revealed that 39.3% of participants have willingness for stem cell donation. Conclusion: It has been found that two third of population expressed lack of knowledge about stem cell transplantation and donation. Also, only 40% of participants showed willingness for donation, and the most common reason for not donating stem cell was the lack of information about stem cell and the value of donation While, increasing level of education was associated with better understanding of stem cell donation and its role in therapy and saving lives. Therefore, suitable campaign, advertising and counseling program for population is recommended to increase level of knowledge and motivation toward stem cell donation.

The oocyte is the female gamete that contributes not only half of the genetic material but also all of the cytoplasm to the zygote, supplying the transcripts, proteins, mitochondria and other components necessary for early embryonic development. The intrinsic oocyte quality is one of the main factors affecting the embryo yield, the implantation rate and the rate of healthy offspring. It is obvious that a fertilized oocyte must reach the blastocyst stage within 6–9 days in the proper culture conditions to have a significant chance of inducing a pregnancy and producing an offspring. The ability to sustain the first week of embryonic development is clearly influenced by the follicular status from which the oocyte is obtained indicating that this developmental potential is inherent within certain oocytes. Since most early embryos that do not reach the blastocyst stage are blocked at or close to the maternal to zygotic transition (MZT)-stage, which occurs at the eight-cell stage in cattle, one could speculate that incompetent oocytes fail to appropriately activate the embryonic genome. Oocyte selection based on glucose-6-phosphate dehydrogenase (G6PDH) activity has been successfully used to differentiate between competent and incompetent bovine oocytes. Recently, molecular regulation of genes regulating biological process of Brilliant Cresyl Blue staining (BCB) selected oocytes and embryos was investigated to explain their variation in quality and developmental potentiality. This short review will highlights some of these efforts that have been done in this interesting area of research.

Brucellosis is a zoonotic infection that is endemic in some Mediterranean countries, North Africa and the Middle East. Brucella is a rare cause of peritonitis in Peritoneal Dialysis (PD) population and in non-dialysis patients alike. We report here a challenging case of PD-related Brucella peritonitis in a 45-year-old Saudi male with late peritonitis that delivered some key learning throughout its course from presentation, diagnosis and treatment to catheter salvage attempts so as to circumvent PD failure. We provide an in-depth review of limited published literature on PD-related Brucella peritonitis (seven cases, and present case) and summarized the data on key clinical characteristics, management and PD technique outcome to benefit nephrologists when encountered with this rare presentation.

We present below a mechanistic molecular approach for development of Anti-Inflammatory biomarkers of Probiotic Bacteria in Fermented Foods. Probiotics are live microorganisms that promote human health by counteracting the noxious toxic gut microflora in human intestine, by modulating of the tight junctions, and by increasing mucin production, enforcing intestinal epithelial cell barrier function, modifying microbial community within the gut intestinal disorders, and improving immune responses associated with chronic inflammation in experimental animal models, collectively enhancing human health. Cytokine secretion by intestinal epithelial cells and macrophages are regulated by probiotics through key signaling pathways such as nuclear factor-κB and mitogen-activated kinases, resulting in alleviation of several disorders such as allergies, diabetes, obesity, heart diseases and cancer. MicroRNAs are small non-coding RNA molecules involved in transcriptional and post-translational regulation of gene expression by inhibiting gene translation. Using in vitro and in vivo approaches in cell lines and mice models to study effects of probiotic conditional media and heat-killed bacterial strains with anti-inflammatory effect to elucidate the mechanisms by which probiotics affect signaling pathways, and by using global cytokine and microRNA gene expression analyses arrroaches to develop biomarkers for studying different pro- and anti-inflammatory activities, and using statistical approaches to analyse the data, we show that cytokines and miRNAs have an essential role in regulation of cancerous and inflammatory bathways. This mechanistic approach will result in developing specific disease biomarkers for the early diagnosis of certain pathogenic states, as well as evaluating the effect of different dietary componenents on developed biomarkers in health states that will promote and enhance human health. Comparing the concordance of the in vitro to the in vivo research findings will confirm the correspondence of both approaches to each other. Moreover, this study will have a major public health relevance in elucidating the role of miRNAs and their targets in inflammation, paving the way to diagnosing and treating of pathogenic human disease stages.

Prednisone-sensitive hypocomplementemia, renal insufficiency, and kidney biopsy demonstrating severe tubulointerstitial nephritis (TIN), storiform fibrosis, and tubulointerstitial immune deposits are typical of IgG4-related tubulointerstitial nephritis and hypocomplementemic interstitial nephritis. A diagnosis of hypocomplementemic interstitial nephritis requires clinical and pathologic exclusion of IgG4-related tubulointerstitial nephritis. We describe a patient with hypocomplementemic interstitial nephritis who did not develop diagnostic features of IgG4 related disease (RD) over 2-year follow-up. We conclude that hypocomplementemic interstitial nephritis could be on a biologic spectrum with IgG4-related disease, but not all cases will develop the abundance of IgG4-positive plasma cells, systemic manifestations, or elevated immunoglobulin levels characteristic of IgG4-RD.

Background: In sickle cell anemia (SCA), compromise of the renal vasculature due to sickled red cells has been recognized. Objectives: To assess the renal function and blood pressure pattern in children with sickle cell anaemia (SCA) presenting in a tertiary institution. Method: A cross-sectional study of patients with sickle cell anaemia (SCA) over six months involving the use of questionnaires, general physical examination, blood pressure, investigations for haemoglobin genotype, urinalysis, serum creatinine, screening for hepatitis B and HIV. Results: 51 children with SCA were seen. The prevalence of impaired renal function as defined by reduced eGFR <90mL/min/1.73m2 in this study was 27.5%, previous hospital admission and blood transfusion were associated with reduction in eGFR but blood pressure did not have significant correlation with the eGFR. The overall mean age at diagnosis of SCA was 4.09 ± 3.33 (years). Conclusion: Impaired renal function is a major comorbid condition in children with SCA. In countries/locations where there is no newborn screening for sickle cell disease, diagnosis is delayed, thus detecting impaired renal function may be delayed, therefore the need for early detection and management is imperative.Introduction