Human mesenchymal stem cells from bone marrow (hMSCs) have broad therapeutic potential. These cells can be are readily isolated from bone marrow by their property to adhere to tissue culture treated culture wares. However, the proliferation rates and other properties of the cells gradually change during expansion. This study aims to validate the protocol of isolation and differentiation of hMSCs from bone marrow for therapeutic applications. Sixty ml of bone marrow was extracted from 5 patients and MSCs were isolated. These were characterized by Flow Cytometry, CFU assay and were differentiated into bone, fat cells and neurocytes. The cells were having healthy morphology. These were positive for the markers CD105, CD90 and CD73 and negative for CD45, CD34 and HLA-DR. The cells could differentiate into fat, bone and neural cells. MSCs from the bone marrow were isolated and differentiated. These cells were morphologically healthy and passed CFU assay. The cells exhibited differentiation potential into bone, fat and neural tissue. These cells can be used in therapeutic applications.

With age the quantity of pluripotent stem cells gradually decreases. It leads to violation of renewal of tissues, including tissues of endocrine organs, at people over 35-40 years old. Artificial formation of the chimeral individual may be used for recovery of the pool of pluripotent stem cells in patients older than 40-50 years old. Transfusions of mononuclear fraction of peripheral blood procured from young donors 18-23 years old with the same blood groups and sex as the recipient (patent of the Russian Federation № 2350340), allows people over 40 years old to reestablish the pool of pluripotent stem cells, the process of tissue renewal and the production of sex hormones, and can also be seen as a promising way to reduce biological age, while providing a significant prolongation of life and while maintaining a high quality of life. Transfusions of mononuclear fraction of peripheral blood are required to be carried out multiple times before the restoration of the numerical strength of the recipients' pool of pluripotent stem cells is complete. The effectiveness of regeneration reconstitution in individuals older than 40 years old upon receiving transfusions of allogeneic pluripotent stem cells depends on the difference in age between the recipient and the young donor. When there is a major difference in age between young donors and recipients over 40 years old, the proliferative potential of pluripotent stem cells of donors (their ability to maintain the number of own pool) is higher than the proliferative potential of the recipient. In response to the formation of colony-stimulating growth factors, this leads to the dominance of transfused and formed colonies in the bone marrow of the donor's pluripotent stem cells over the analogous cells of recipients when renewing all of their tissues. The latter occurs mainly due to the donors' stem cells.

One of the major causes of reduced vision over the age of 50 is age-related macular degeneration (AMD). Although such a common pathology, there are no current guidelines for the first-line treatment of dry AMD. The aim of this study is to evaluate the therapeutic effects of high omega-3 fatty acids as anti-inflammatory agents in two sub-groups of dry AMD patients with 1) mild to moderate visual impairment and 2) with severe visual impairment (blindness). The key feature of this investigation is the frequent monitoring of the levels of specific fatty acids in patient's blood in order to adjust the treatment dose within the ideal therapeutic window. Following the positive outcome from our initial observational studies in patients with dry AMD, who demonstrated significant improvement in visual acuity (gain of ≥ 1 line of vision in 4.5 months) when taking a total of 5 g/day eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), additional studies were encouraged. The latest data which is presented in this chapter suggests that the eyes which had the greatest gain in vision (≥ 15 letters gain at 6 months) were from patients with mild to moderate visual impairment, who were taking between 5-7.5 g/day EPA and DHA and had a ratio of arachidonic acid (AA)/EPA < 2. In addition, a sub-group of dry AMD patients with severe visual impairment (< 6/60), showed significant increase in their visual acuity only 3 months following treatment with omega-3 fatty acids. The preliminary results indicate a promising therapeutic regime for dry AMD and perhaps for other types of retinopathies as well. Although initial results are encouraging, further investigations are necessary to establish a better understanding of the mode of action of these supplements and to observe their long-term effects.

Cervical cancer is a challenging pathologic entity because of its lack of response to conventional chemotherapy. Imiquimod is a synthetic analogue which seems to activate skin immune cells, acting as a Toll-like receptor 7 agonist. Previous studies in the field of cervical cancer have showed that its application may play a significant role in the treatment of cervical HPV infection with or without cervical intraepithelial neoplasia (CIN). In the present study we investigate the therapeutic potential of imiquimod in a cervical carcinoma cell line and evaluate whether the expression of HLA-G and OCT-4 is altered during this treatment. HeLa cells were cultured in Dulbecco's modified Eagle medium and treated with 200 μl of imiquimod diluted solution (50 μg/ml). Cultured cells were allocated in four groups 1) control, 2) DMSO only, 3) DMSO and imiquimod for 48 hours, 4) DMSO and imiquimod for 72 hours. In the imiquimod treated cell lines we observed a significant reduction of viable cells at 48 and 72 hours (p = .001). The relative expression analysis of OCT-4 and HLA-G genes at 48 and 72 hours did not reveal significant differences after imiquimod treatment. Imiquimod effectively reduces the percentage of viable HeLa cells and should be further evaluated in future clinical trials. This effect takes place as of 48 hours after its initial application and seems to persist at least until 72 hours. HLA-G and OCT-4 expression is not affected by this type of treatment.

The concept of extramedullary hematopoiesis for production of organ-specific antigen presenting cells has importance in immunity in terms of the compartmentalisation of the immune response in different tissue sites. A new and distinct dendritic-like antigen presenting cell subtype is described which is dependent on the spleen microenvironment for development. Cells arise by a unique developmental pathway distinct from other dendritic cells (DC). In particular, a self-renewing progenitor of these cells has been identified in spleen upstream of the earliest DC progenitor currently identified in bone marrow. This progenitor depends on the splenic microenvironment for maintenance and proliferation, adding further support for spleen as a site for hematopoiesis.

Nearly 2 million people annually die prematurely from various illness contributed by indoor air pollutants (IAP). Such pollutants affect the lungs leading to diseases ranging from bronchial diseases to malignant lung cancer. Stem cells (SC) with the property of self-renewal, pluripotency, and capability of homing into tumors and metastases, have been reported to be promising in treatment of lung cancer. In this review, we have tried to understand the role of components of IAP affect the SC. Although very few studies have been conducted in these lines, existing reports suggest that IAP causes damage to stem cells and their niches thereby reducing successful chances of autologous stem cell transplantation and therapy. The mechanism by which components of IAP affects the functioning of stem cells thus conferring toxicity remains unexplored. The future scope of this review lies in revealing answer to underlying questions of repair and modulation of stem cells in therapeutic treatment of lung diseases.

Regeneration of bony defects caused by periodontal disease continues to be a challenge for clinicians. Application of stem cells from different tissue sources and scaffolds for regeneration have been reported in animal models but clinical studies with long term follow-ups are limited. Herein we report the three years follow-up of the application of autologous bone marrow mononuclear cells (BMMNCs) embedded in a thermo-reversible gelation polymer (TGP) for periodontal regeneration. A 23-year female patient with advanced periodontitis (class IV gingival recession, probing pocket depth (PPD) of 5 mm and 6 mm in relation to mandibular lateral and central incisors respectively, and clinical attachment level (CAL) of 13 mm) correlated with radiographic evidence of severe horizontal bone loss extending up to the apex of mandibular incisors was selected for the treatment. After debridement, the defect was implanted with BMMNCs impregnated in TGP. Then the clinical parameters and radiographic evaluation were made at periodic intervals of 6, 12, 24 and 36 months. At six months, significant improvement with the clinical parameters (PPD had reduced to 2 mm, clinical attachment level had improved by 6 mm) was observed. At 36 months, the radiograph revealed bone regeneration with improvement in vertical and horizontal bone height. Transplantation of BMMNCs in a novel TGP is safe and results in a relatively significant and stable clinical outcome in horizontal alveolar bony defects.

Tissue is frequently damaged or lost in injury and disease. There has been an increasing interest in stem cell applications and tissue engineering approaches in surgical practice to deal with damaged or lost tissue. Tissue engineering is an exciting strategy being explored to deal with damaged or lost tissue. It is the science of generating tissue using molecular and cellular techniques, combined with material engineering principles, to replace tissue. This could be in the form of cells with or without matrices. Although there have been developments in almost all surgical disciplines, the greatest advances are being made in orthopaedics, especially in cartilage repair. This is due to many factors including the familiarity with bone marrow derived mesenchymal stem cells and cartilage being a relatively simpler tissue to engineer. Unfortunately significant hurdles remain to be overcome in many areas before tissue engineering becomes more routinely used in clinical practice. Cells used in tissue engineering could be autologous, allogeneic or xenogeneic. The cells could be stem cells or cells further down the differentiation pathway. The use of embryonic stem cells is associated with religious, political and social concerns, but the use of adult stem cells is generally well accepted. Stem cells have been identified in a number of adult tissues, albeit in small numbers. In addition to bone marrow, mesenchymal stem cells have been identified in a number of tissues including adipose tissue and fat pad. The mesenchymal stem cells are generally isolated from the tissue and expanded in culture. These cells can be differentiated down a particular differentiation pathway e.g. osteoblast or chondrocyte, using predefined culture conditions before being used for clinical applications. In this paper stem cells are discussed including their various sources and their differentiation potential.

Acute myeloid leukemia has emerged as a paradigm for the concept of the cancer stem cell. This hypothesis presumes that the disease is maintained by a rare population of leukemia-initiating stem cells which have acquired genetic or epigenetic changes. It is most likely that a single (epi)genetic event will not be sufficient to cause leukemia, but that a number of sequential events are required. Similar to normal hematopoietic stem cells, both intrinsic as well as extrinsic factors that arise from the bone marrow niche, provide essential cues that regulate cell fate decisions such as leukemic stem cell self-renewal and differentiation. In this chapter, we will review the current understanding of genetic and epigenetic abnormalities that underlie the process of leukemic transformation, and will discuss which events potentially co-operate to induce leukemia.

Adult tissues contain quiescent reservoirs of multipotent somatic stem cells and pluripotent embryonic-like stem cells (ELSCs). Credited with regenerative properties gold is used across both -contemporary and -ancient medicines. Here, we show that gold exerted these effects by enhancing the pool of pluripotent ELSC while improving their stemness. We used hESCs as an in-vitro model to understand if gold could enhance self-renewal and pluripotency. Swarna-bhasma (SB), an ancient Indian gold microparticulate (41.1 nm), preparation, reduced spontaneous-differentiation, improved self-renewal, pluripotency and proliferation of hESCs. Colloidal gold-nanoparticles (GNP) (15.59 nm) were tested to confirm that the observations were attributable to nanoparticulate-gold. SB and GNP exposure: maintained -stemness, -karyotypic stability, enhanced pluripotency till day-12, increased average colony-sizes, and reduced the number of autonomously-derived differentiated FGFR1 positive fibroblast-niche-cells/colony. Particulate-gold induced upregulation of FGFR1 and IGF2 expression, and decrease in IGF1 secretion indicates IGF1/2 mediated support for enhanced pluripotency and self-renewal in hESCs.