Neurologic disorders are caused by a either neural cell loss or neurologic cell injury processes. Management of these disorders would therefore be to replace the lost cells, clear the pathological hallmarks or repair cell function. Stem cells offer the possibility of a renewable source of replacement cells and tissues as a form of treatment in neurological regeneration.

An explanation of how: The origen of first stem cells on earth. The fact of cell differentiation. The fact of tissue culture. This paper is about a new theory on appearance of the first stem cells on earth. This theory explains that how and when the first animal and plant cells have arisen on the earth. This theory also says ( unlike scientists opinions )stem cells can be seen in unicellular organisms as well. According to this theory the course of appearance of the first stem cells is similar to endosymbiosis. The difference is that genes of two symbiotic cells have been merged. Nevertheless both cells can separate from each other but after separation genes of two symbiotic cells remain with them as safekeeping, thus they are able to generate the cell itself and the symbiotic cell too. Scientists call " distinction " the generation of the first stem cells from the cell concluded by symbiotic. Scientists are able to force cells to generate its symbiotic cell by tissue culture, but they don't know the nature and origin of the issue and can't answer the question the first stem cells how and when and where have come to exist.

The urge to discover a natural pluripotent stem cells lead to a breakthrough in the field of regenerative medicine with the discovery of induced pluripotent stem cells (iPSCs).  iPSCs are a type of pluripotent stem cell generated in vitro from adult cells by introducing four transcription factors (OCT4, SOX2, MYC, KLF4) termed Yamanaka Factors.  The hype with iPSCs is that they would offer an unlimited supply of autologous cells that could be used clinically, themselves and their differentiated end-products, without the risk of immune rejection.  However, problems arose with autologous transplantation of iPSCs and their differentiated end-products, including high cost and excessive manufacturing time, making them, in most cases, clinically impractical to use.  Therefore, currently the solution is to use donor iPSC cell lines to produce allogeneic “off-the-shelf” tissue matching cell products.  Although this has reduced the manufacturing time, it is still a relatively expensive exercise that clinically demands immunosuppression.  Hypothetically, a naturally occurring PSC found in abundance would have low cost, less manufacturing time, and used autologously, would eliminate immunosuppression protocols.  However, the surge in iPSC research has hampered the search for a naturally occurring pluripotent stem cell. We have discovered, using immunohistochemical analysis, a population of cells in human peripheral blood that are pluripotent, easy to isolate, and abundant.  This discovered population of cells range between 1 to 5 million cells per ml of plasma, are relatively small in diameter (<5um), express all four Yamanaka factors (OCT4, SOX2, MYC, KLF4), stain positive for the Kyoto Probe (KP-1), and express Nanog, CD133, CXCR4, SSEA3 and SSEA4. These easily obtainable, naturally occurring PSCs from peripheral blood may have far reaching positive consequences in the field of regenerative medicine and bio-banking.

Expansion of T cells, especially CD8 ⁺ cells, is very important for cell therapy approached in diseases related to the immune system. Finding signaling pathways and molecules involved in improving the quality and quantity of T cells can be a great help in compensating the lost lymphocytes in the body. In this 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  in 4-1BBL , Akt inhibitor, interleukin 7 and 15 expansion media.

 

Conventional human pluripotent stem cell (hPSC) cultures require high concentrations of expensive human fibroblast growth factor 2 (hFGF-2) for hPSC self-renewal and pluripotency in defined media for long-term culture. The hPSC culture media need to be changed every day partly due to the hFGF-2 thermal instability in solution at 37°C. It has been known that the binding site of human DJ-1 (hDJ-1), also known as PARK-7 is FGF receptor-1. In the present study, for the first time, we have demonstrated that recombinant protein human FGF-2 can replace hDJ-1 in the essential eight media to maintain the pluripotency of H9 human embryonic stem cells (hESCs) under feeder-free condition. After more than ten passages, H9 hESCS cultured with human FGF-2 or human DJ-1 successfully sustained the distinctive hESC morphology. Furthermore, H9 hESCs revealed high expression levels of pluripotency markers including SSEA4, Tra1-60, Oct4, Nanog, and Alkaline phosphatase. DNA microarray revealed that more than 97% of the 21,448 tested genes, including the pluripotency markers, Sox2, Nanog, Klf4, Lin28A, Lin28B, and Myc, have similar mRNA levels between the two groups. Karyotyping revealed no chromosome abnormalities in both groups. They also differentiated sufficiently into three germ layers by forming in vitro embryoid bodies and in vivo teratomas. There were moderate difference in H9 hESCS in both groups was shown in the real-time PCR assay using several pluripotency markers and three germ layer markers. The proliferation rate measured at different concentration of growth factors and the structural analysis of mitochondria using transmission electron microscopy demonstrated the distinguishable feature of H9 hESCs in two groups, namely hFGF2 and hDJ-1. On the whole, in-house made recombinant protein hDJ-1 can maintain the self-renewal and the pluripotency of H9 hESCs in a feeder-free system for long-term without alteration of their characteristics

Hematopoietic stem and progenitor cells (HSPCs) are the key regulators of hematopoiesis which give rise to different, mature and committed lineages. Exposure to acute whole-body radiation results in the loss of HSPCs leading to the inability of the system to generate differentiated lineages which ultimately cause hematopoietic form of acute radiation syndrome (hs-ARS). Currently no safe and effective molecule as a radiation countermeasure is available for human applications. Due to this bone marrow transplantation (BMT) has become an indispensable strategy for the management of radiation over-exposed victims, hematopoietic malignancies and planned chemotherapy induced bone marrow depression. Several strategies have been employed to achieve successful Hematopoietic stem cell transplantation (HSCT), capable of enhancing HSC homing and engraftment potential but at a high cost. Here in this study, we have reported an inexpensive strategy involving short-term ex-vivo exposure of bone marrow mononuclear cells (BMMNCs) to a small molecule which successfully enhances the HSPCs proliferation, migration and homing to its BM niche after transplantation. Results indicate that ex-vivo exposure led to a significant increase in CXCR4 expression and migration of HSPCs towards SDF-1α as evident from in-vitro studies. In-vivo data displayed that ex-vivo exposure of BMMNCs with the molecule resulted in a significant increase in the number of homed cells to the BM niche as compared to the vehicle treated group. Hence, the above strategy suggests an efficient and cost-effective method for achieving successful HSC transplantation for a variety of scenarios including management of hs-ARS.

The pancreatic duct system contains a number of epithelial cell types. These are the minor cells of total pancreas comprising 10% of all other pancreatic cells. On the other hands, they are exclusively involved in a number of very serious pathological diseases including lethal pancreatic adenocarcinoma, cystic fibrosis and pancreatitis. We established an efficient strategy to direct human pluripotent stem cells, including human embryonic stem cells (hESCs) and an induced pluripotent stem cell (iPSC) line derived from patients with cystic fibrosis, to differentiate into pancreatic ductal epithelial cells (PDECs). After purification, more than 98% of hESC-derived PDECs expressed functional cystic fibrosis transmembrane conductance regulator (CFTR) protein. In addition, iPSC lines were derived from a patient with CF carrying compound frameshift and mRNA splicing mutations and were differentiated to PDECs. PDECs derived from Weill Cornell cystic fibrosis (WCCF)-iPSCs showed defective expression of mature CFTR protein and impaired chloride ion channel activity, recapitulating functional defects of patients with CF at the cellular level. These studies provide a new methodology to derive pure PDECs expressing CFTR and establish a "disease in a dish" platform to identify drug candidates to rescue the pancreatic defects of patients with CF.  This is the landmark achievement towards the cutting edge modeling of pancreatic epithelial cell originated lethal diseases with more accuracy and faster validation.