Journal of Stem Cells最新文献

Objective: Key modalities of integrative medicine known to rejuvenate the mind and body are meditation, yoga, and controlled diet. It has been shown previously that intensive or prolonged mind and body therapies (MBT) may have beneficial effects on the well-being of healthy people and in patients. Telomerase activity and levels of peripheral blood adult pluripotent stem cells (PB-APSC) are reliable markers of long-term well-being that are known to decrease with age. The objective of this study is to understand the effect of our MBT program on telomerase activity and stem cells in blood collected from the participants.

Design: Here, we have investigated the effects of an intensive three weeks MBT retreat on telomerase activity and the peripheral blood stem cells in participants before and after the MBT. A total of 108 people were enrolled in the study; 38 men and 70 women (aged 18-90) randomly assigned for the study.

Results: Telomerase activity was greater in retreat participants at the end of the MBT retreat. About 45% of people showed more than one-fold increase of telomerase activity after our MBT program. Furthermore, about 27% of people showed more pronounced fold increase (2-fold) in telomerase activity after the MBT. In addition, a substantial percentage of people (about 90%) exhibited increased stem cell counts after the MBT.

Conclusions: The data suggest increased telomerase activity and stem cells count in peripheral blood from MBT retreat participants that may lead to increased longevity and better quality of life at latter age.

Nanotechnology techniques have a prominent role in the current technical and scientific scene. The layer-by-layer (LbL) deposition allows obtaining nanostructures with sophisticated multilayer, using a simple, but versatile technique. This procedure, which is used to coat and functionalize surfaces with nanometer- thick films, has applications in bioengineering, medicine, chemistry, materials and chemical engineering among other areas. Chitosan is a biomaterial, coming from the chitin, a very abundant polymer in nature, which has been recently tested as scaffolds. In this experiment we test the hypothesis that the hyaluronic acid-chitosan polyelectrolyte multilayer biofilm would be a good substrate to the adherence of equine mesenchymal stem cells derived from bone marrow. The results showed that these biofilms accelerate the process of cell adhesion on smooth surfaces, allowing a constant cell growth and creating a great option to cover surgical materials.

Objective: Duchenne muscular dystrophy (DMD) is a musculo-degenerative disease characterized by lack of dystrophin production with no definite cure available currently. Discarded umbilical cord is a potential source of mesenchymal stem cells which are non-immunogenic and can be used for transplantation in allogenic set ups. Given the regenerative and anti-inflammatory properties of mesenchymal stem cells (MSCs), here we investigated its role in the cellular therapy of DMD patients.

Design: This is a single-blinded study conducted in various hospitals of India situated in Mumbai, Delhi, and Lucknow. Inclusion criteria for enrolling the patients in the study were boys aged between 5 to 18 years, absence of dystrophin in the immunohistochemistry of muscle biopsy and mutation in dystrophin gene in cytogenetic analysis. The exclusion criteria were presence of dystrophin in the muscle biopsy, patients on corticosteroids etc. UC-MSCs (2 millions/kg body weight) were administered through IV and IM injection. Muscle power in muscles of proximal upper limb, distal upper limb, proximal lower limb, distal lower limb, hip flexors, hip extensors, hip abductors, and paraspinal muscles were measured in 11 DMD patients after UC-MSCs transplantation and were followed for up to 3 years (average follow up 1.5 years). 5 DMD patients did not receive any UC-MSCs transplantation and served as the control group.

Results: The treatment group (N = 11 at baseline) had a pretransplantation strength of 3.45 ± 1.0357 and 4.090 ± 0.8312 in muscles of proximal upper limb and distal upper limb respectively. After 1 year (N = 9) these strengths remained stable with an average of 3.78 (1.03) and 4.22 (0.83). In contrast, the control group (N = 5) has a pre-transplantation strength of 3.6 (0.54) and 4 (1) in the proximal and distal upper limb respectively. After 1 year, (N = 5) 3/5 subjects had a slight but not statistically significant decrease in the proximal upper limb, mean 3.0 (1.0) and 5/5 had a lunit decrease in strength, mean 3.0 (1.0). The treatment group had a pre-transplantation strength of 2.0909 ± 0.8312 and 3.1181 ± 0.8738 in muscles of distal and proximal lower limbs respectively. At 1 year (N = 9), 4/9 subjects had a 1 unit increase in strength in the distal lower limb (mean 3.78 (0.97)) and 8/9 subjects had a lunit increase in strength in the proximal lower limb, mean 3.11 (1.05). The control group has a mean of 3.41 (0.54) and 3.0 (1.0) at baseline in the distal and proximal lower limb respectively. By 1 year, 3/5 subjects had a 1 unit decrease (mean 2.8 (0.45)) and 5/5 had a lunit decrease, mean 2.0 (1.0) in distal and proximal lower limb strength. Stability in muscle function was also achieved in muscles of hip flexors, hip extensors, hip abductors, and paraspinal muscles at one year as compared to untreated group.

Conclusion: UC-MSCs administration not only resulted in the s

Glioblastomamultiforme (GBM) is the most common malignant and aggressive primary tumor of the brain in adults and characterized by a heterogeneous population of cells that are genetically unstable, highly infiltrative, angiogenic, and resistant to chemotherapy. Considerable efforts being devoted to identifying the molecular basis of resistance in GBM and exploring novel therapeutic targets that may improve overall survival. Several independent DNA repair mechanisms that normally safeguard genome integrity can facilitate drug resistance and cancer cell survival by removing chemotherapy- induced adducts. The recent data suggest that the most important mechanism of resistance to alkylating agents is the DNA repair enzyme O6-methylguanine methyltransferase (MGMT). Although, the treatment failure is a result of a number of causes, but currently, it has been demonstrated that a highly tumorigenic subpopulation of cancer cells called glioblastoma stem cells (GSCs) display relative resistance to radiation and chemotherapy. In fact, GBM stem cells express high levels of MGMT and this may account for GBM resistance following chemotherapy. GSCs also contribute to tumor growth through the stimulation of angiogenesis, which has been shown to be a useful therapeutic target in the treatment of recurrent or progressive malignant gliomas. In this review, we summarize the chemoresistance mechanisms of GBMs (to alkylating agents), with a special focus on the role of cancer stem cells.

Hematopoietic stem cells (HSC) are multipotent cells that produce the various lineages of blood and HSC transplantations (HSCT) are widely used to reconstitute damaged bone marrow (BM). Over time, HSCT has evolved for the treatment of non-blood diseases as well, brain in particular. However, HSCT required total myeloablation through irradiation and/or chemotherapy for the treatment of BM-related diseases, and HSCs are difficult to safely deliver in large amounts into the brain. In blood disorders, for a minimal myelosuppression to be sufficient and allow donor cells to engraft, it is necessary to determine the minimal percentage of normal BM cells needed to achieve phenotypic correction. Recent studies on animal models of ?-thalassemia and sickle cell disease (SCD), through Competitive Repopulation Assay (CRA) following lethal irradiation of recipients, demonstrated that an average of 25% normal BM cells allows the production of enough normal red blood cells to significantly correct the ?-thalassemia and SCD phenotypes, at the levels of BM, blood, histology, and survival, with normal donor cells contributing to 50-60% of peripheral red blood cells. Further assays using mild myelosuppression showed that long term sustained phenotypic correction can be obtained for both diseases through a novel transplantation strategy based on modulating four parameters: dose of irradiation/myelosuppression, number of transplanted cells, timing of cell injections, and number of cell doses. Through a minimal dose of irradiation of 1Gy (100 Rads) or 2Gy, two injections of BM cells within the first 24h after myelosuppression resulted in engraftment in 100% of mice and a sustained therapeutic mixed chimerism in ?-thalassemia, while three to four injections were needed to achieve a similar outcome in SCD. Following the success of these trials, we modified this novel HSCT strategy and applied it to determine whether we can protect mice from lethal stroke induced through the Middle Cerebral Artery Occlusion (MCAO). Ischemia/reperfusion resulted in a major infarct that propagated over time to encompass ~70% of the affected hemisphere. When two doses of HSCs were injected at 2h and 24h after the reperfusion, 40% of mice survived, visible neurological defects disappeared, and the infarct size was reduced by two to four fold. Histological examination of brains in surviving mice revealed very few donor cells in the recipient brains, decreased total neurons count and increased glial cell numbers. These data suggest that the neuro-protection was not dependent on cell-supplementation, but rather the protection is manifested likely through growth factor secretion. Combined, these studies create a novel HSCT approach that has proved efficient for the treatment of various disorders. A "window of opportunity" exists for each disease where the donor cells should be administered, and multiple injections of donor HSCs can rescue diseases that would otherwise not be treatable. We

Bird embryogenesis takes place in a relatively protected environment that can be manipulated especially well in domestic fowl (chickens) where incubation has long been a commercial process. The embryonic developmental process has been shown to begin in the oviduct such that the embryo has attained either the blastodermal and/or gastrulation stage of development at oviposition. Bird embryos can be affected by "maternal effects," and by environmental conditions during the pre-incubation and incubation periods. "Maternal effects" has been described as an evolutionary mechanism that has provided the mother, by hormonal deposition into the yolk, with the potential to proactively influence the development of her progeny by exposing them to her particular hormonal pattern in such a manner as to influence their ability to cope with the expected wide range of environmental conditions that may occur post-hatching. Another important aspect of "maternal effects" is the effect of the maternal nutrient intake on progeny traits. From a commercial broiler chicken production perspective, it has been established that greater cumulative nutrient intake by the hen during her pullet rearing phase prior to photostimulation resulted in faster growing broiler progeny. Generally, maternal effects on progeny, which have both a genetic and an environmental component represented by yolk hormones deposition and embryo nutrient utilization, have an important effect on the development of a wide range of progeny traits. Furthermore, commercial embryo development during pre-incubation storage and incubation, as well as during incubation per se has been shown to largely depend upon temperature, while other environmental factors that include egg position during storage, and the amount of H2O and CO2 lost by the egg and the subsequent effect on albumen pH and height during storage have become important environmental factors to be considered for successful embryogenesis under commercial conditions. Manipulating environmental temperature during the period of egg storage, during the intermediate pre-incubation period, and incubation period per se has been found to significantly affect embryo development, hatching progress, chick quality at hatching, and chick development post-hatching. These temperature manipulations have also been shown to affect the acquisition of thermotolerance to subsequent post-hatching thermal challenge. This chapter will focus on: a. "maternal effects" on embryo and post-hatching development; b. environmental effects during the post-ovipositional period of egg storage, the intermediate pre-incubation period, and incubation period per se on chick embryogenesis and subsequent post-hatching growth and development; and c. effects of temperature manipulations during the pre-incubation and incubation periods on acquisition of thermotolerance and development of secondary sexual characteristics in broiler chickens.

Stem cells can be defined as cells that have the capacity to self-renew and the ability to generate differentiated progeny or multiple cell lineages. True stem cells can turn into any type of cells, while progenitor cells are more or less committed to becoming cell types of a particular tissue. Human corneal epithelial stem cells (CESCs) represent a great example and model of adult stem or progenitor cells. Human CESCs have been identified to locate in the basal epithelial layer of the limbus, and thus also referred as to limbal stem cells. We would like to use the both terms, stem and progenitor cells in this chapter based on previous use in the literature for more than two decades. Although the CESCs have been identified to reside at the limbus and many stem cell markers have been proposed, there is no consensus to date regarding the definitive markers for CESCs, and identification and isolation of these cells are still challenging. Based on evaluation of a variety of proposed markers, we have characterized that the CESCs located in the basal layer of human limbal epithelium are small primitive cells expressing three patterns of molecular markers, which represent a unique phenotype of putative corneal epithelial stem or progenitor cells. Based on adult stem cell criteria and the putative limbal stem cell phenotype, our group has attempted to enrich for human CESCs through novel approaches including cell-sizing, adhering to extracellular matrix collagen type IV, and cell sorting for side population or for expression of ABCG2 or connexin 43 cell surface markers. The 5 clonogenic populations isolated from limbal epithelium and its cultures by different methods show the properties that are characteristics of adult stem/progenitor cells: 1) relatively undifferentiated, 2) high proliferative potential, 3) self-renewal. Expansion and cultivation of corneal epithelial progenitor cells have been achieved using different methods, such as limbal tissue explant culture, and limbal epithelial cell suspension co-culture with mouse 3T3 fibroblast feed layer. To avoid the use of xeno-components, two cell lines of commercial human fibroblasts have been identified that support human corneal epithelial regeneration, and have potential use in replacing mouse 3T3 cells for corneal tissue bioengineering. The concept of CESCs has formed the basis for identifying a class of blinding diseases that display features of corneal epithelial stem cell deficiency or limbal stem cell deficiency (LSCD), where the limbal epithelium is damaged. LSCD is characterized by persistent or recurrent epithelial defects, ulceration, corneal vascularization, chronic inflammation, scarring, and conjunctivalization (conjunctival epithelial ingrowth). Only transplantation of CESCs can restore vision. Due to an increasing shortage of corneal donors, corneal tissue engineering is becoming an important discipline that holds great promise for corneal reconstruction. CESCs and optical substr

Endothelial progenitor cells (EPC) are mobilized after myocardial infarction (MI) from the bone marrow to injured sites of the heart where they participate in cardiac repair by revascularization of ischemic tissues. Endothelial progenitor cells have been actively studied, but their exact phenotype and regenerative properties are still controversial. Small trials with progenitor cells of different origins showed modest clinical benefits. It is assumed that a better understanding of the biology of EPC will contribute to improve their therapeutic potential. MicroRNAs (miRNAs) are small single-stranded non-coding RNAs that modulate gene expression by interacting post transcriptionally with protein-coding RNAs. MicroRNAs regulate multiple biological processes involved in cardiac development and disease. While many studies addressed the role of miRNAs in cardiac cells, less is known of the effect of miRNAs in EPC. Recent studies showed that miRNAs indeed regulate the biology of EPC. Since novel technologies to enhance or blunt the functions of miRNAs have been recently developed, it is conceivable that miRNAs may become promising new therapeutic tools. This article will review the recent advances in the knowledge of the effects of miRNAs in EPC and will discuss how miRNAs could be manipulated to improve the regenerative capacities of EPC in the diseased heart.

Aim: Evaluation of safety in using unmatched human allogeneic umbilical cord blood cells for therapeutic use in individuals with non-haematopoietic degenerative conditions.

Background: The historical data and several recent immunological arguments suggest the therapeutic use of allogeneic Cord Blood Mononuclear Cells (CBMNCs), as these cells do not elicit immune response. Customarily, HLA matched cord blood MNCs are used along with prolonged immunosuppression in treatment of haematological conditions. Lately, unmatched CBMNCs are widely used in case of unavailability of HLA matched cord blood. There have been suggestions for using unmatched allogeneic cord blood MNCs for degenerative conditions without an immunoconditioning regimen.

Method: 49 patients with non-haematopoietic degenerative conditions were treated with HLA-unmatched allogeneic hUCB MNCs. Intrathecal/I.V injections (1-2 million cells/kg body weight) were given. Clinical, biochemical and haematological adverse events were evaluated.

Results: The haematological and biochemical parameters showed no major deviation from the normal. Clinically, no acute adverse effects or GVHD were observed with the used dosage.

Conclusion: This study supports/suggests clinical safety in therapeutic medical use of unmatched allogeneic CBMNCs when used at low dosage in non-haematopoietic degenerative conditions.

Background: Umbilical Mesenchymal Stem Cells possess immunoregulatory capacities that have been permissive to allogenic transplantation. Recent animal studies have demonstrated histologically that bone marrow- derived mesenchymal stem cells (MSCs) may enhance the regeneration of periodontal defects in dogs by differentiating MSCs into cementoblasts, osteoblasts and periodontal fibroblasts.

Aim: To compare the clinical efficacy between stem cells in combination with PLA/PGA membrane and subepithelial connective tissue graft (SCTG) in the treatment of multiple gingival recession defects.

Methods: Twenty four patients aged between 20 to 33 years (mean age 27.41 ± 1.06 years) with multiple gingival recession defects on labial or buccal surface of the teeth in the aesthetic zone either in maxilla or mandible were treated. The test group was treated using stem cells cultured on bioresorbable PLA/PGA membrane, while control group was treated using SCTG. Following parameters were assessed, Plaque Index (PI),Gingival Bleeding Point Index (GBI), Relative gingival margin level (RGML), Relative attachment level (RAL) and Probing pocket depth (PPD) Results: In the test group, mean percent defect coverage was 72.43 ± 13.55 % and the predictability was 41.17% for root coverage i.e 14 of 34 defects, while in the control group, mean percent defect coverage was 82.06 ± 10.99 % and the predictability was 50 % for root coverage i.e 15 of 30 defects.

Conclusion: Stem cells in combination with bioresorbable PLA/PGA membrane was effective for root coverage resulted in a significant reduction in gingival recession, greater gain in CAL and WKG. Stem cells in combination with bioresorbable PLA/PGA membrane resulted in significantly higher CAL gain than SCTG.