Mesenchymal Stem Cell (MSCs) Therapy for Ischemic Heart Disease: A Promising Frontier

Although tremendous progress has been made in conventional treatment for ischemic heart disease, it still remains a major cause of death and disability. Cell-based therapeutics holds an exciting frontier of research for complete cardiac recuperation. The capacity of diverse stem and progenitor cells to stimulate cardiac renewal has been analysed, with promising results in both pre-clinical and clinical trials. Mesenchymal stem cells have been ascertained to have regenerative ability via a variety of mechanisms, including differentiation from the mesoderm lineage, immunomodulatory properties, and paracrine effects. Also, their availability, maintenance, and ability to replenish endogenous stem cell niches have rendered them suitable for front-line research. This review schemes to outline the use of mesenchymal stem cell therapeutics for ischemic heart disease, their characteristics, the potent mechanisms of mesenchymal stem cell-based heart regeneration, and highlight preclinical data. Additionally, we discuss the results of the clinical trials to date as well as ongoing clinical trials on ischemic heart disease.     

HIV type 1 subtypes among blood donors in the Mbeya region of southwest Tanzania

HIV-1 is endemic in Tanzania where three different subtypes, A, C, and D, have been identified. Information on HIV-1 genetic diversity is crucial to define requirements for an effective vaccine, in regions where HIV-1 vaccine trials are planned. To define the subtype distribution of HIV-1 in the Mbeya region of southwest Tanzania, peripheral blood mononuclear cells (PBMC) and plasma were obtained from 36 discarded HIV seropositive blood units. Multiregion hybridization assay (MHA) was performed on both PBMC DNA and plasma RNA to determine the subtype distribution. Twenty virtually full-length HIV-1 sequences were amplified from the extracted DNA, sequenced, and phylogenetically analyzed. Subtype distribution determined by all three assays was comparable. More than 50% of the samples analyzed were subtype C, followed by a high proportion of subtype C-containing intersubtype recombinants. Based on this work, subtype C appears to be the prevalent subtype in southwest Tanzania, followed by a high proportion of intersubtype recombinants.     

Hematologic,immunologic reconstitution,and outcome of 342 autologous peripheral blood stem cell transplantations after cryopreservation in a −80°C mechanical freezer and preserved less than 6 months

BACKGROUND: Controlled‐rate freezing and storage in nitrogen is the standard technique for cryopreservation of peripheral hematopoietic progenitor cells (PHPCs) but presents high cost and dimethyl sulfoxide (DMSO) toxicity. Cryopreservation at ?80°C, by uncontrolled rate freezing with only 3.5% DMSO, preserves the functional capacities of PHPCs, produces successful engraftment, and reduces toxicity during infusion. STUDY DESIGN AND METHODS: Long‐term hematopoietic and immunologic reconstitution for 342 autografts (311 adults, 31 children) after PHPCs were cryopreserved at ?80°C was studied at 3, 6, and 12 months. The median (range) storage time of PHPCs cryopreserved was 1.7 (0.1‐5.99) months. RESULTS: Hemoglobin (Hb), white blood cells, and platelets (PLTs) reach normal values to trilineage at 12 months for 39% patients. Multivariate analysis shows a significant impact on CD34+ infused and on conditioning regimen for PLTs. Hb was influenced by growth factor administration at 3 months. Long‐term recovery is also highly dependent on blood counts (Hb, PLT, and neutrophil) at start of high‐dose chemotherapy. Only 43% of patients had reached normal lymphocyte values at 12 months after transplant, and a profound CD4+ T‐lymphocyte deficit remained, as others reported. CONCLUSION: Transplantation with PHPCs cryopreserved at ?80°C for no more than 6 months is satisfactory for long‐term hematopoietic and immunologic reconstitution, even if a profound CD4+ T lymphocyte deficit persists at 1 year. This easier and cheaper cryopreservation method also leads to successful engraftment.     

Effectiveness and Safety Assessment of Mist Tonica, a Herbal Haematinic

Anaemia is a widespread public health problem, and in Ghana it is the fourth leading cause of hospital admissions and the second factor contributing to death. Mist Tonica, an herbal haematinic produced by the Centre for Scientific Research into Plant Medicine (CSRPM), Ghana, was assessed for its effectiveness and safety in humans after Ethics Committee approval. Clinically established anaemic-patients aged, 13 years and above, with haemoglobin levels less than 11.5 g/dl and 13.5g/dl for females and males respectively were treated with Mist Tonica, 8.96 g/ 40 mls three times daily for two weeks . The mean haemoglobin rise per week caused by Mist Tonica was 1.92 (0.76) g/dl, range (1.66 – 2.55) g/dl/week and over 88 % of the patients on Mist Tonica had their appetite for food improved. Haematological profile, liver and kidney functions were not adversely affected by Mist Tonica. Results of the study suggest that Mist Tonica is an effective and safe herbal haematinic.     

Effects of sleep deprivation on extracellular serotonin in hippocampus and frontal cortex of the rat

Sleep deprivation improves the mood of depressed patients, but the exact mechanism behind this effect is unclear. An enhancement of serotonergic neurotransmission has been suggested. In this study, we used in vivo microdialysis to monitor extracellular serotonin in the hippocampus and the frontal cortex of rats during an 8 h sleep deprivation period. These brain regions were selected since both have been implicated in depression. The behavioral state of the animal was continuously monitored by polygraphic recordings during the experiment. Sleep deprivation produced a gradual decline in extracellular serotonin levels, both in the hippocampus and in the frontal cortex. In order to investigate whether the reduction in serotonin was due to other factors than sleep deprivation, i.e. time of day effect, another experiment was performed. Here animals were allowed to sleep during most of the recording period. This experiment showed the expected changes in extracellular serotonin levels: consistently higher levels in the awake, non-sleep deprived animals compared to during sleep, but no time of day effect. The reduction in extracellular serotonin during sleep deprivation may suggest that serotonin does not play a major role in the mood-elevating effect of sleep deprivation. However, since 5-HT levels are strongly behavioral state dependent, by eliminating sleep, there may be a net increase in serotonergic neurotransmission during the sleep deprivation period.     

Generation of potent T(h)1 responses from patients with lymphoid malignancies after differentiation of B lymphocytes into dendritic-like cells

Dendritic cells (DC) are a group of potent antigen-presenting cells (APC) specialized for initiating T cell immune responses. They originate from the bone marrow and upon stimulation with bacterial products, cytokines or CD40 ligation they acquire the ability to migrate to the secondary lymphoid organs. In vitro DC can be generated from human CD34(+) bone marrow cells and CD14(+) peripheral blood monocytes after culture with different cytokine combinations. Since most leukemic cells and tumors in general are devoid of APC capacities, various strategies have been used to increase their recognition and confer the capacity of antigen presentation on them. Because of our interest in the design of vaccine immunotherapy protocols for the adjuvant treatment of patients with lymphoid malignancies (LM), we chose to explore the capacity of human acute lymphoblastic leukemia, chronic lymphocytic leukemia and plasma cell leukemia to differentiate into cells with APC and DC features. Our results among a sample of 10 patients demonstrate that such approach is feasible. Leukemic cells could be induced in the presence of IL-4 and CD40L to exhibit a DC morphology with a phenotype of mature DC-like cells. They could also induce a potent proliferative response in naive CD4(+) T cells. In addition, they expressed chemokine receptor CCR7 and CD62L, and could drive T cells towards a T(h)1 response with secretion of IFN-gamma. Our strategy leading to increased LM cell immunogenicity may have potential clinical applications and LM appear to be attracting candidates for adjuvant vaccination and adoptive immunotherapy.     

Involvement of neutrophilic granulocytes in the uptake of biodegradable non-stealth and stealth nanoparticles in guinea pig

The in vivo behavior of monomethoxypoly(ethylene oxide)-poly(lactic acid) (MPEO20-PLA45/PLA (75/25)) nanoparticles in comparison with PLA ones was studied in guinea pig. Indeed, the aim of this study was to bring to the fore the in vivo stealth character of these copolymer nanoparticles and to identify the phagocytic circulating cells involved in their uptake. After the intravascular administration of fluorescent nanoparticles (rubrene), their phagocytosis by granulocytes and monocytes was assayed by flow cytometry. At the same time, the evolution of the number of these phagocytic cells was realized in order to identify their function in the nanoparticle uptake. Finally, a histological study of the spleen (30 h after the nanoparticle administration) was investigated to highlight the splenic trapping of these stealth nanoparticles. This study has shown that the phagocytic circulating cells involved in the nanoparticle uptake were mainly neutrophilic granulocytes and some of them were found in the spleen.     

Relationship between children physical activity,inflammatory mediators and lymphocyte activation: possible impact of social isolation (COVID-19)

Sport Sciences for Health - Lifestyle and body composition may be simultaneously responsible for immune response modulation. This study aimed to compare plasmatic adipokines concentration and...