Technology integration within the elementary classroom setting

The purpose of this paper is to examine technology integration in the elementary classroom setting. Technology is now considered to be an important part of a child\u27s educational experience. Research has determined that students do not learn the same way they did years ago, thus schools are changing their methodologies on how to best serve the 21st century student. However, technology integration can not happen all at once; there are many barriers to technology integration. Some examples would be environmental barriers, curriculum issues, and the personal beliefs of the teachers. School districts are addressing these problems to ensure that their students are getting an education that is enriched with technology. To overcome some of the barriers, like having time to learn how to use technology in the classroom, schools are providing staff development to support teachers in their learning. One-to-one computing and mobile labs are all different ways that schools can support technology integration. Colleges and universities are also developing programs so pre-service teachers will get technology training before entering the classroom. In order for students to compete in the 21st century they have to be taught with the 21 st century tools

Bone marrow stromal cells as a genetic platformfor systemic delivery of therapeutic proteins in vivo : human factor IX model

Background Hemophilia B is an X-linked bleeding disorder that results from a deficiency in functional coagulation factor IX (hFIX). In patients lacking FIX, the intrinsic coagulation pathway is disrupted leading to a lifelong, debilitating and sometimes fatal disease. Methods We have developed an ex vivo gene therapy system using genetically modified bone marrow stromal cells (BMSCs) as a platform for sustained delivery of therapeutic proteins into the general circulation. This model exploits the ability of BMSCs to form localized ectopic ossicles when transplanted in vivo . BMSCs were transduced with MFG-hFIX, a retroviral construct directing the expression of hFIX. The biological activity of hFIX expressed by these cells was assessed in vitro and in vivo . Results Transduced cells produced biologically active hFIX in vitro with a specific activity of 90% and expressed hFIX at levels of ∼497 ng/10 6 cells/24 h and 322 ng/10 6 cells/24 h for human and porcine cells, respectively. The secretion of hFIX was confirmed by Western blot analysis of the conditioned medium using a hFIX-specific antibody. Transduced BMSCs (8 × 10 6 cells per animal) were transplanted within scaffolds into subcutaneous sites in immunocompromised mice. At 1 week post-implantation, serum samples contained hFIX at levels greater than 25 ng/ml. Circulating levels of hFIX gradually decreased to 11.5 ng/ml at 1 month post-implantation and declined to a stable level at 6.1 ng/ml at 4 months. Conclusions These findings demonstrate that genetically modified BMSCs can continuously secrete biologically active hFIX from self-contained ectopic ossicles in vivo , and thus represent a novel delivery system for releasing therapeutic proteins into the circulation. Copyright © 2002 John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/35232/1/292_ftp.pd

Skeletal homeostasis in tissue-engineered bone

Tissue-engineering strategies to stimulate bone regeneration may offer an alternative approach to conventional orthopaedic and maxillofacial surgical therapies. Over the last decade, significant advances have been accomplished in developing biomimetic matrices, growth factors, cell transplantation and gene delivery therapeutics to support new bone growth. However, it is not known if tissue-engineered bone recapitulates the biology of normal skeletal tissue in response to physiologic cues. Here, we report that bone formed by the differentiation of transplanted murine bone marrow stromal cells (BMSCs) responds to a systemically delivered calciotropic hormone. Ectopic ossicles in mice exposed to catabolic doses of parathyroid hormone (PTH) had increased numbers of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts as compared to control mice. In contrast, treatment with anabolic doses of PTH promoted a marked increase in trabecular bone mass as analyzed by microcomputed tomography and histomorphometry. Our findings demonstrate that bone formed from transplanted BMSCs is responsive to normal physiologic signals, and can be augmented by the addition of a systemic anabolic agent. Because multiple and distinct ossicles can be generated in a single animal, this versatile system may be used to: (a) elucidate cellular/molecular mechanisms in bone regeneration; (b) study cell-to-cell interactions in the bone marrow microenvironment in health and disease; and (c) evaluate the efficacy of osteotropic agents that modulate bone turnover in vivo. © 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34920/1/1100210516_ftp.pd

Stem Cell Therapy Remediates Reconstruction of the Craniofacial Skeleton After Radiation Therapy

This study utilized transplanted bone marrow stromal cells (BMSCs) as a cellular replacement therapy to remedy radiation-induced injury and restore impaired new bone formation during distraction osteogenesis (DO). BMSC therapy brought about the successful generation of new bone and significantly improved both the rate and quality of a bony union of irradiated, distracted [X-ray radiation therapy (XRT)/DO] murine mandibles to the level of nonirradiated DO animals. The bone mineral density and bone volume fraction were also significantly improved by the BMSC replacement therapy showing no difference when compared to nonirradiated animals. Finally, a biomechanical analysis examining the yield, failure load, and ultimate load also demonstrated a significantly improved structural integrity in BMSC-treated XRT/DO mandibles over XRT/DO alone. These results indicate that administration of BMSCs intraoperatively to a radiated distraction gap can function as an adequate stimulant to rescue the ability for irradiated bone to undergo DO and produce a healed regenerate of a vastly superior quality and strength. We believe that the fundamental information on the optimization of bone regeneration in the irradiated mandible provided by this work has immense potential to be translated from the bench to the bedside to lead to improved therapeutic options for patients suffering from the disastrous sequelae of radiation therapy.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140201/1/scd.2012.0472.pd

Human Transgene-Free Amniotic-Fluid-Derived Induced Pluripotent Stem Cells for Autologous Cell Therapy

The establishment of a reliable prenatal source of autologous, transgene-free progenitor cells has enormous potential in the development of regenerative-medicine-based therapies for infants born with devastating birth defects. Here, we show that a largely CD117-negative population of human amniotic fluid mesenchymal stromal cells (AF-MSCs) obtained from fetuses with or without prenatally diagnosed anomalies are readily abundant and have limited baseline differentiation potential when compared with bone-marrow-derived MSCs and other somatic cell types. Nonetheless, the AF-MSCs could be easily reprogrammed into induced pluripotent stem cells (iPSCs) using nonintegrating Sendai viral vectors encoding for OCT4, SOX2, KLF4, and cMYC. The iPSCs were virtually indistinguishable from human embryonic stem cells in multiple assays and could be used to generate a relatively homogeneous population of neural progenitors, expressing PAX6, SOX2, SOX3, Musashi-1, and PSA-NCAM, for potential use in neurologic diseases. Further, these neural progenitors showed engraftment potential in vivo and were capable of differentiating into mature neurons and astrocytes in vitro. This study demonstrates the usefulness of AF-MSCs as an excellent source for the generation of human transgene-free iPSCs ideally suited for autologous perinatal regenerative medicine applications.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140204/1/scd.2014.0110.pd

Erythropoietin Couples Hematopoiesis with Bone Formation

It is well established that bleeding activates the hematopoietic system to regenerate the loss of mature blood elements. We have shown that hematopoietic stem cells (HSCs) isolated from animals challenged with an acute bleed regulate osteoblast differentiation from marrow stromal cells. This suggests that HSCs participate in bone formation where the molecular basis for this activity is the production of BMP2 and BMP6 by HSCs. Yet, what stimulates HSCs to produce BMPs is unclear.In this study, we demonstrate that erythropoietin (Epo) activates Jak-Stat signaling pathways in HSCs which leads to the production of BMPs. Critically, Epo also directly activates mesenchymal cells to form osteoblasts in vitro, which in vivo leads to bone formation. Importantly, Epo first activates osteoclastogenesis which is later followed by osteoblastogenesis that is induced by either Epo directly or the expression of BMPs by HSCs to form bone.These data for the first time demonstrate that Epo regulates the formation of bone by both direct and indirect pathways, and further demonstrates the exquisite coupling between hematopoiesis and osteopoiesis in the marrow

Comprehensive in vitro and in vivo studies of novel melt-derived Nb-substituted 45S5 bioglass reveal its enhanced bioactive properties for bone healing

The present work presents and discusses the results of a comprehensive study on the bioactive properties of Nb-substituted silicate glass derived from 45S5 bioglass. In vitro and in vivo experiments were performed. We undertook three different types of in vitro analyses: (i) investigation of the kinetics of chemical reactivity and the bioactivity of Nb-substituted glass in simulated body fluid (SBF) by 31P MASNMR spectroscopy, (ii) determination of ionic leaching profiles in buffered solution by inductively coupled plasma optical emission spectrometry (ICP-OES), and (iii) assessment of the compatibility and osteogenic differentiation of human embryonic stem cells (hESCs) treated with dissolution products of different compositions of Nb-substituted glass. The results revealed that Nb-substituted glass is not toxic to hESCs. Moreover, adding up to 1.3 mol% of Nb2O5 to 45S5 bioglass significantly enhanced its osteogenic capacity. For the in vivo experiments, trial glass rods were implanted into circular defects in rat tibia in order to evaluate their biocompatibility and bioactivity. Results showed all Nb-containing glass was biocompatible and that the addition of 1.3 mol% of Nb2O5, replacing phosphorous, increases the osteostimulation of bioglass. Therefore, these results support the assertion that Nb-substituted glass is suitable for biomedical applications

Amelioration of Streptozotocin-Induced Diabetes in Mice with Cells Derived from Human Marrow Stromal Cells

Pluri-potent bone marrow stromal cells (MSCs) provide an attractive opportunity to generate unlimited glucose-responsive insulin-producing cells for the treatment of diabetes. We explored the potential for human MSCs (hMSCs) to be differentiated into glucose-responsive cells through a non-viral genetic reprogramming approach.Two HMSC lines were transfected with three genes: PDX-1, NeuroD1 and Ngn3 without subsequent selection, followed by differentiation induction in vitro and transplantation into diabetic mice. Human MSCs expressed mRNAs of the archetypal stem cell markers: Sox2, Oct4, Nanog and CD34, and the endocrine cell markers: PDX-1, NeuroD1, Ngn3, and Nkx6.1. Following gene transfection and differentiation induction, hMSCs expressed insulin in vitro, but were not glucose regulated. After transplantation, hMSCs differentiated further and approximately 12.5% of the grafted cells expressed insulin. The graft bearing kidneys contained mRNA of insulin and other key genes required for the functions of beta cells. Mice transplanted with manipulated hMSCs showed reduced blood glucose levels (from 18.9+/-0.75 to 7.63+/-1.63 mM). 13 of the 16 mice became normoglycaemic (6.9+/-0.64 mM), despite the failure to detect the expression of SUR1, a K(+)-ATP channel component required for regulation of insulin secretion.Our data confirm that hMSCs can be induced to express insulin sufficient to reduce blood glucose in a diabetic mouse model. Our triple gene approach has created cells that seem less glucose responsive in vitro but which become more efficient after transplantation. The maturation process requires further study, particularly the in vivo factors influencing the differentiation, in order to scale up for clinical purposes

Gene-enhanced tissue engineering for dental hard tissue regeneration: (1) overview and practical considerations

Gene-based therapies for tissue regeneration involve delivering a specific gene to a target tissue with the goal of changing the phenotype or protein expression profile of the recipient cell; the ultimate goal being to form specific tissues required for regeneration. One of the principal advantages of this approach is that it provides for a sustained delivery of physiologic levels of the growth factor of interest. This manuscript will review the principals of gene-enhanced tissue engineering and the techniques of introducing DNA into cells. Part 2 will review recent advances in gene-based therapies for dental hard tissue regeneration, specifically as it pertains to dentin regeneration/pulp capping and periodontal regeneration