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The Promise of Induced Pluripotent Stem Cells (iPSCs …

By Sykes24Tracey

Charles A. Goldthwaite, Jr., Ph.D.

In 2006, researchers at Kyoto University in Japan identified conditions that would allow specialized adult cells to be genetically "reprogrammed" to assume a stem cell-like state. These adult cells, called induced pluripotent stem cells (iPSCs), were reprogrammed to an embryonic stem cell-like state by introducing genes important for maintaining the essential properties of embryonic stem cells (ESCs). Since this initial discovery, researchers have rapidly improved the techniques to generate iPSCs, creating a powerful new way to "de-differentiate" cells whose developmental fates had been previously assumed to be determined.

Although much additional research is needed, investigators are beginning to focus on the potential utility of iPSCs as a tool for drug development, modeling of disease, and transplantation medicine. The idea that a patient's tissues could provide him/ her a copious, immune-matched supply of pluripotent cells has captured the imagination of researchers and clinicians worldwide. Furthermore, ethical issues associated with the production of ESCs do not apply to iPSCs, which offer a non-controversial strategy to generate patient-specific stem cell lines. As an introduction to this exciting new field of stem cell research, this chapter will review the characteristics of iPSCs, the technical challenges that must be overcome before this strategy can be deployed, and the cells' potential applications to regenerative medicine.

As noted in other chapters, stem cells represent a precious commodity. Although present in embryonic and adult tissues, practical considerations such as obtaining embryonic tissues and isolating relatively rare cell types have limited the large-scale production of populations of pure stem cells (see the Chapter, "Alternate Methods for Preparing Pluripotent Stem Cells" for details). As such, the logistical challenges of isolating, culturing, purifying, and differentiating stem cell lines that are extracted from tissues have led researchers to explore options for "creating" pluripotent cells using existing non-pluripotent cells. Coaxing abundant, readily available differentiated cells to pluripotency would in principle eliminate the search for rare cells while providing the opportunity to culture clinically useful quantities of stem-like cells.

One strategy to accomplish this goal is nuclear reprogramming, a technique that involves experimentally inducing a stable change in the nucleus of a mature cell that can then be maintained and replicated as the cell divides through mitosis. These changes are most frequently associated with the reacquisition of a pluripotent state, thereby endowing the cell with developmental potential. The strategy has historically been carried out using techniques such as somatic cell nuclear transfer (SCNT),1,2 altered nuclear transfer (ANT),3,4 and methods to fuse somatic cells with ESCs5,6 (see "Alternate Methods for Preparing Pluripotent Stem Cells" for details of these approaches). From a clinical perspective, these methods feature several drawbacks, such as the creation of an embryo or the development of hybrid cells that are not viable to treat disease. However, in 2006, these efforts informed the development of nuclear reprogramming in vitro, the breakthrough method that creates iPSCs.

This approach involves taking mature "somatic" cells from an adult and introducing the genes that encode critical transcription factor proteins, which themselves regulate the function of other genes important for early steps in embryonic development (See Fig. 10.1). In the initial 2006 study, it was reported that only four transcription factors (Oct4, Sox2, Klf4, and c-Myc) were required to reprogram mouse fibroblasts (cells found in the skin and other connective tissue) to an embryonic stem celllike state by forcing them to express genes important for maintaining the defining properties of ESCs.7 These factors were chosen because they were known to be involved in the maintenance of pluripotency, which is the capability to generate all other cell types of the body. The newly-created iPSCs were found to be highly similar to ESCs and could be established after several weeks in culture.7,8 In 2007, two different research groups reached a new milestone by deriving iPSCs from human cells, using either the original four genes9 or a different combination containing Oct4, Sox2, Nanog, and Lin28.10 Since then, researchers have reported generating iPSCs from somatic tissues of the monkey11 and rat.12,13

However, these original methods of reprogramming are inefficient, yielding iPSCs in less than 1% of the starting adult cells.14,15 The type of adult cell used also affects efficiency; fibroblasts require more time for factor expression and have lower efficiency of reprogramming than do human keratinocytes, mouse liver and stomach cells, or mouse neural stem cells.1419

Several approaches have been investigated to improve reprogramming efficiency and decrease potentially detrimental side effects of the reprogramming process. Since the retroviruses used to deliver the four transcription factors in the earliest studies can potentially cause mutagenesis (see below), researchers have investigated whether all four factors are absolutely necessary. In particular, the gene c-Myc is known to promote tumor growth in some cases, which would negatively affect iPSC usefulness in transplantation therapies. To this end, researchers tested a three-factor approach that uses the orphan nuclear receptor Esrrb with Oct4 and Sox2, and were able to convert mouse embryonic fibroblasts to iPSCs.20 This achievement corroborates other reports that c-Myc is dispensable for direct reprogramming of mouse fibroblasts.21 Subsequent studies have further reduced the number of genes required for reprogramming,2226 and researchers continue to identify chemicals that can either substitute for or enhance the efficiency of transcription factors in this process.27 These breakthroughs continue to inform and to simplify the reprogramming process, thereby advancing the field toward the generation of patient-specific stem cells for clinical application. However, as the next section will discuss, the method by which transcription factors are delivered to the somatic cells is critical to their potential use in the clinic.

Figure 10.1. Generating Induced Pluripotent Stem Cells (iPSCs).

2008 Terese Winslow

Reprogramming poses several challenges for researchers who hope to apply it to regenerative medicine. To deliver the desired transcription factors, the DNA that encodes their production must be introduced and integrated into the genome of the somatic cells. Early efforts to generate iPSCs accomplished this goal using retroviral vectors. A retrovirus is an RNA virus that uses an enzyme, reverse transcriptase, to replicate in a host cell and subsequently produce DNA from its RNA genome. This DNA incorporates into the host's genome, allowing the virus to replicate as part of the host cell's DNA. However, the forced expression of these genes cannot be controlled fully, leading to unpredictable effects.28 While other types of integrating viruses, such as lentiviruses, can increase the efficiency of reprogramming,16 the expression of viral transgenes remains a critical clinical issue. Given the dual needs of reducing the drawbacks of viral integration and maximizing reprogramming efficiency, researchers are exploring a number of strategies to reprogram cells in the absence of integrating viral vectors2730 or to use potentially more efficient integrative approaches.31,32

Before reprogramming can be considered for use as a clinical tool, the efficiency of the process must improve substantially. Although researchers have begun to identify the myriad molecular pathways that are implicated in reprogramming somatic cells,15 much more basic research will be required to identify the full spectrum of events that enable this process. Simply adding transcription factors to a population of differentiated cells does not guarantee reprogrammingthe low efficiency of reprogramming in vitro suggests that additional rare events are necessary to generate iPSCs, and the efficiency of reprogramming decreases even further with fibroblasts that have been cultured for long time periods.33 Furthermore, the differentiation stage of the starting cell appears to impact directly the reprogramming efficiency; mouse hematopoietic stem and progenitor cells give rise to iPSCs up to 300 times more efficiently than do their terminally-differentiated B- and T-cell counterparts.34 As this field continues to develop, researchers are exploring the reprogramming of stem or adult progenitor cells from mice24,25,34,35 and humans23,26 as one strategy to increase efficiency compared to that observed with mature cells.

As these discussions suggest, clinical application of iPSCs will require safe and highly efficient generation of stem cells. As scientists increase their understanding of the molecular mechanisms that underlie reprogramming, they will be able to identify the cell types and conditions that most effectively enable the process and use this information to design tools for widespread use. Clinical application of these cells will require methods to reprogram cells while minimizing DNA alterations. To this end, researchers have found ways to introduce combinations of factors in a single viral "cassette" into a known genetic location.36 Evolving tools such as these will enable researchers to induce programming more safely, thereby informing basic iPSC research and moving this technology closer to clinical application.

ESCs and iPSCs are created using different strategies and conditions, leading researchers to ask whether the cell types are truly equivalent. To assess this issue, investigators have begun extensive comparisons to determine pluripotency, gene expression, and function of differentiated cell derivatives. Ultimately, the two cell types exhibit some differences, yet they are remarkably similar in many key aspects that could impact their application to regenerative medicine. Future experiments will determine the clinical significance (if any) of the observed differences between the cell types.

Other than their derivation from adult tissues, iPSCs meet the defining criteria for ESCs. Mouse and human iPSCs demonstrate important characteristics of pluripotent stem cells, including expressing stem cell markers, forming tumors containing cell types from all three primitive embryonic layers, and displaying the capacity to contribute to many different tissues when injected into mouse embryos at a very early stage of development. Initially, it was unclear that iPSCs were truly pluripotent, as early iPSC lines contributed to mouse embryonic development but failed to produce live-born progeny as do ESCs. In late 2009, however, several research groups reported mouse iPSC lines that are capable of producing live births,37,38 noting that the cells maintain a pluripotent potential that is "very close to" that of ESCs.38 Therefore, iPSCs appear to be truly pluripotent, although they are less efficient than ESCs with respect to differentiating into all cell types.38 In addition, the two cell types appear to have similar defense mechanisms to thwart the production of DNA-damaging reactive oxygen species, thereby conferring the cells with comparable capabilities to maintain genomic integrity.39

Undifferentiated iPSCs appear molecularly indistinguishable from ESCs. However, comparative genomic analyses reveal differences between the two cell types. For example, hundreds of genes are differentially expressed in ESCs and iPSCs,40 and there appear to be subtle but detectable differences in epigenetic methylation between the two cell types.41,42 Genomic differences are to be expected; it has been reported that gene-expression profiles of iPSCs and ESCs from the same species differ no more than observed variability among individual ESC lines.43 It should be noted that the functional implications of these findings are presently unknown, and observed differences may ultimately prove functionally inconsequential.44

Recently, some of the researchers who first generated human iPSCs compared the ability of iPSCs and human ESCs to differentiate into neural cells (e.g., neurons and glia).45 Their results demonstrated that both cell types follow the same steps and time course during differentiation. However, although human ESCs differentiate into neural cells with a similar efficiency regardless of the cell line used, iPSC-derived neural cells demonstrate lower efficiency and greater variability when differentiating into neural cells. These observations occurred regardless of which of several iPSC-generation protocols were used to reprogram the original cell to the pluripotent state. Experimental evidence suggests that individual iPSC lines may be "epigenetically unique" and predisposed to generate cells of a particular lineage. However, the authors believe that improvements to the culturing techniques may be able to overcome the variability and inefficiency described in this report.

These findings underpin the importance of understanding the inherent variability among discrete cell populations, whether they are iPSCs or ESCs. Characterizing the variability among iPSC lines will be crucial to apply the cells clinically. Indeed, the factors that make each iPSC line unique may also delay the cells' widespread use, as differences among the cell lines will affect comparisons and potentially influence their clinical behavior. For example, successfully modeling disease requires being able to identify the cellular differences between patients and controls that lead to dysfunction. These differences must be framed in the context of the biologic variability inherent in a given patient population. If iPSC lines are to be used to model disease or screen candidate drugs, then variability among lines must be minimized and characterized fully so that researchers can understand how their observed results match to the biology of the disease being studied. As such, standardized assays and methods will become increasingly important for the clinical application of iPSCs, and controls must be developed that account for variability among the iPSCs and their derivatives.

Additionally, researchers must understand the factors that initiate reprogramming towards pluripotency in different cell types. A recent report has identified one factor that initiates reprogramming in human fibroblasts,46 setting the groundwork for developing predictive models to identify those cells that will become iPSCs. An iPSC may carry a genetic "memory" of the cell type that it once was, and this "memory" will likely influence its ability to be reprogrammed. Understanding how this memory varies among different cell types and tissues will be necessary to reprogram successfully.

iPSCs have the potential to become multipurpose research and clinical tools to understand and model diseases, develop and screen candidate drugs, and deliver cell-replacement therapy to support regenerative medicine. This section will explore the possibilities and the challenges that accompany these medical applications, with the caveat that some uses are more immediate than others. For example, researchers currently use stem cells to test/screen drugs or as study material to identify molecules or genes implicated in regeneration. Conducting experiments or testing candidate drugs on human cells grown in culture enables researchers to understand fundamental principles and relationships that will ultimately inform the use of stem cells as a source of tissue for transplantation. Therefore, using iPSCs in cell-replacement therapies is a future application of these cells, albeit one that has tremendous clinical potential. The following discussion will highlight recent efforts toward this goal while recognizing the challenges that must be overcome for these cells to reach the clinic.

Reprogramming technology offers the potential to treat many diseases, including Alzheimer's disease, Parkinson's disease, cardiovascular disease, diabetes, and amyotrophic lateral sclerosis (ALS; also known as Lou Gehrig's disease). In theory, easily-accessible cell types (such as skin fibroblasts) could be biopsied from a patient and reprogrammed, effectively recapitulating the patient's disease in a culture dish. Such cells could then serve as the basis for autologous cell replacement therapy. Because the source cells originate within the patient, immune rejection of the differentiated derivatives would be minimized. As a result, the need for immunosuppressive drugs to accompany the cell transplant would be lessened and perhaps eliminated altogether. In addition, the reprogrammed cells could be directed to produce the cell types that are compromised or destroyed by the disease in question. A recent experiment has demonstrated the proof of principle in this regard,47 as iPSCs derived from a patient with ALS were directed to differentiate into motor neurons, which are the cells that are destroyed in the disease.

Although much additional basic research will be required before iPSCs can be applied in the clinic, these cells represent multi-purpose tools for medical research. Using the techniques described in this article, researchers are now generating myriad disease-specific iPSCs. For example, dermal fibroblasts and bone marrow-derived mesencyhmal cells have been used to establish iPSCs from patients with a variety of diseases, including ALS, adenosine deaminase deficiency-related severe combined immunodeficiency, Shwachman- Bodian-Diamond syndrome, Gaucher disease type III, Duchenne and Becker muscular dystrophies, Parkinson's disease, Huntington's disease, type 1 diabetes mellitus, Down syndrome/trisomy 21, and spinal muscular atrophy.4749 iPSCs created from patients diagnosed with a specific genetically-inherited disease can then be used to model disease pathology. For example, iPSCs created from skin fibroblasts taken from a child with spinal muscular atrophy were used to generate motor neurons that showed selective deficits compared to those derived from the child's unaffected mother.48 As iPSCs illuminate the development of normal and disease-specific pathologic tissues, it is expected that discoveries made using these cells will inform future drug development or other therapeutic interventions.

One particularly appealing aspect of iPSCs is that, in theory, they can be directed to differentiate into a specified lineage that will support treatment or tissue regeneration. Thus, somatic cells from a patient with cardiovascular disease could be used to generate iPSCs that could then be directed to give rise to functional adult cardiac muscle cells (cardiomyocytes) that replace diseased heart tissue, and so forth. Yet while iPSCs have great potential as sources of adult mature cells, much remains to be learned about the processes by which these cells differentiate. For example, iPSCs created from human50 and murine fibroblasts5153 can give rise to functional cardiomyocytes that display hallmark cardiac action potentials. However, the maturation process into cardiomyocytes is impaired when iPSCs are usedcardiac development of iPSCs is delayed compared to that seen with cardiomyocytes derived from ESCs or fetal tissue. Furthermore, variation exists in the expression of genetic markers in the iPSC-derived cardiac cells as compared to that seen in ESC-derived cardiomyocytes. Therefore, iPSC-derived cardiomyocytes demonstrate normal commitment but impaired maturation, and it is unclear whether observed defects are due to technical (e.g., incomplete reprogramming of iPSCs) or biological barriers (e.g., functional impairment due to genetic factors). Thus, before these cells can be used for therapy, it will be critical to distinguish between iPSC-specific and disease-specific phenotypes.

However, it must be noted that this emerging field is continually evolving; additional basic iPSC research will be required in parallel with the development of disease models. Although the reprogramming technology that creates iPSCs is currently imperfect, these cells will likely impact future therapy, and "imperfect" cells can illuminate many areas related to regenerative medicine. However, iPSC-derived cells that will be used for therapy will require extensive characterization relative to what is sufficient to support disease modeling studies. To this end, researchers have begun to use imaging techniques to observe cells that are undergoing reprogramming to distinguish true iPSCs from partially-reprogrammed cells.54 The potential for tumor formation must also be addressed fully before any iPSC derivatives can be considered for applied cell therapy. Furthermore, in proposed autologous therapy applications, somatic DNA mutations (e.g., non-inherited mutations that have accumulated during the person's lifetime) retained in the iPSCs and their derivatives could potentially impact downstream cellular function or promote tumor formation (an issue that may possibly be circumvented by creating iPSCs from a "youthful" cell source such as umbilical cord blood).55 Whether these issues will prove consequential when weighed against the cells' therapeutic potential remains to be determined. While the promise of iPSCs is great, the current levels of understanding of the cells' biology, variability, and utility must also increase greatly before iPSCs become standard tools for regenerative medicine.

Since their discovery four years ago, induced pluripotent stem cells have captured the imagination of researchers and clinicians seeking to develop patient-specific therapies. Reprogramming adult tissues to embryonic-like states has countless prospective applications to regenerative medicine, drug development, and basic research on stem cells and developmental processes. To this point, a PubMed search conducted in April 2010 using the term "induced pluripotent stem cells" (which was coined in 2006) returned more than 1400 publications, indicating a highly active and rapidlydeveloping research field.

However, many technical and basic science issues remain before the promise offered by iPSC technology can be realized fully. For putative regenerative medicine applications, patient safety is the foremost consideration. Standardized methods must be developed to characterize iPSCs and their derivatives. Furthermore, reprogramming has demonstrated a proof of-principle, yet the process is currently too inefficient for routine clinical application. Thus, unraveling the molecular mechanisms that govern reprogramming is a critical first step toward standardizing protocols. A grasp on the molecular underpinnings of the process will shed light on the differences between iPSCs and ESCs (and determine whether these differences are clinically significant). Moreover, as researchers delve more deeply into this field, the effects of donor cell populations can be compared to support a given application; i.e., do muscle-derived iPSCs produce more muscle than skin-derived cells? Based on the exciting developments in this area to date, induced pluripotent stem cells will likely support future therapeutic interventions, either directly or as research tools to establish novel models for degenerative disease that will inform drug development. While much remains to be learned in the field of iPSC research, the development of reprogramming techniques represents a breakthrough that will ultimately open many new avenues of research and therapy.

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Medical imaging Wikipedia IPS Cell Therapy IPS Cell …

By Sykes24Tracey

This article is about imaging techniques and modalities for the human body. For imaging of animals in research, see Preclinical imaging.

Medical imaging is the technique and process of creating visual representations of the interior of a body for clinical analysis and medical intervention, as well as visual representation of the function of some organs or tissues (physiology). Medical imaging seeks to reveal internal structures hidden by the skin and bones, as well as to diagnose and treat disease. Medical imaging also establishes a database of normal anatomy and physiology to make it possible to identify abnormalities. Although imaging of removed organs and tissues can be performed for medical reasons, such procedures are usually considered part of pathology instead of medical imaging.

As a discipline and in its widest sense, it is part of biological imaging and incorporates radiology which uses the imaging technologies of X-ray radiography, magnetic resonance imaging, medical ultrasonography or ultrasound, endoscopy, elastography, tactile imaging, thermography, medical photography and nuclear medicine functional imaging techniques as positron emission tomography (PET) and Single-photon emission computed tomography (SPECT).

Measurement and recording techniques which are not primarily designed to produce images, such as electroencephalography (EEG), magnetoencephalography (MEG), electrocardiography (ECG), and others represent other technologies which produce data susceptible to representation as a parameter graph vs. time or maps which contain data about the measurement locations. In a limited comparison these technologies can be considered as forms of medical imaging in another discipline.

Up until 2010, 5billion medical imaging studies had been conducted worldwide.[1] Radiation exposure from medical imaging in 2006 made up about 50% of total ionizing radiation exposure in the United States.[2]

Medical imaging is often perceived to designate the set of techniques that noninvasively produce images of the internal aspect of the body. In this restricted sense, medical imaging can be seen as the solution of mathematical inverse problems. This means that cause (the properties of living tissue) is inferred from effect (the observed signal). In the case of medical ultrasonography, the probe consists of ultrasonic pressure waves and echoes that go inside the tissue to show the internal structure. In the case of projectional radiography, the probe uses X-ray radiation, which is absorbed at different rates by different tissue types such as bone, muscle and fat.

The term noninvasive is used to denote a procedure where no instrument is introduced into a patients body which is the case for most imaging techniques used.

In the clinical context, invisible light medical imaging is generally equated to radiology or clinical imaging and the medical practitioner responsible for interpreting (and sometimes acquiring) the images is a radiologist. Visible light medical imaging involves digital video or still pictures that can be seen without special equipment. Dermatology and wound care are two modalities that use visible light imagery. Diagnostic radiography designates the technical aspects of medical imaging and in particular the acquisition of medical images. The radiographer or radiologic technologist is usually responsible for acquiring medical images of diagnostic quality, although some radiological interventions are performed by radiologists.

As a field of scientific investigation, medical imaging constitutes a sub-discipline of biomedical engineering, medical physics or medicine depending on the context: Research and development in the area of instrumentation, image acquisition (e.g., radiography), modeling and quantification are usually the preserve of biomedical engineering, medical physics, and computer science; Research into the application and interpretation of medical images is usually the preserve of radiology and the medical sub-discipline relevant to medical condition or area of medical science (neuroscience, cardiology, psychiatry, psychology, etc.) under investigation. Many of the techniques developed for medical imaging also have scientific and industrial applications.[3]

Two forms of radiographic images are in use in medical imaging. Projection radiography and fluoroscopy, with the latter being useful for catheter guidance. These 2D techniques are still in wide use despite the advance of 3D tomography due to the low cost, high resolution, and depending on application, lower radiation dosages. This imaging modality utilizes a wide beam of x rays for image acquisition and is the first imaging technique available in modern medicine.

A magnetic resonance imaging instrument (MRI scanner), or nuclear magnetic resonance (NMR) imaging scanner as it was originally known, uses powerful magnets to polarize and excite hydrogen nuclei (i.e., single protons) of water molecules in human tissue, producing a detectable signal which is spatially encoded, resulting in images of the body.[4] The MRI machine emits a radio frequency (RF) pulse at the resonant frequency of the hydrogen atoms on water molecules. Radio frequency antennas (RF coils) send the pulse to the area of the body to be examined. The RF pulse is absorbed by protons, causing their direction with respect to the primary magnetic field to change. When the RF pulse is turned off, the protons relax back to alignment with the primary magnet and emit radio-waves in the process. This radio-frequency emission from the hydrogen-atoms on water is what is detected and reconstructed into an image. The resonant frequency of a spinning magnetic dipole (of which protons are one example) is called the Larmor frequency and is determined by the strength of the main magnetic field and the chemical environment of the nuclei of interest. MRI uses three electromagnetic fields: a very strong (typically 1.5 to 3 teslas) static magnetic field to polarize the hydrogen nuclei, called the primary field; gradient fields that can be modified to vary in space and time (on the order of 1kHz) for spatial encoding, often simply called gradients; and a spatially homogeneous radio-frequency (RF) field for manipulation of the hydrogen nuclei to produce measurable signals, collected through an RF antenna.

Like CT, MRI traditionally creates a two dimensional image of a thin slice of the body and is therefore considered a tomographic imaging technique. Modern MRI instruments are capable of producing images in the form of 3D blocks, which may be considered a generalization of the single-slice, tomographic, concept. Unlike CT, MRI does not involve the use of ionizing radiation and is therefore not associated with the same health hazards. For example, because MRI has only been in use since the early 1980s, there are no known long-term effects of exposure to strong static fields (this is the subject of some debate; see Safety in MRI) and therefore there is no limit to the number of scans to which an individual can be subjected, in contrast with X-ray and CT. However, there are well-identified health risks associated with tissue heating from exposure to the RF field and the presence of implanted devices in the body, such as pace makers. These risks are strictly controlled as part of the design of the instrument and the scanning protocols used.

Because CT and MRI are sensitive to different tissue properties, the appearance of the images obtained with the two techniques differ markedly. In CT, X-rays must be blocked by some form of dense tissue to create an image, so the image quality when looking at soft tissues will be poor. In MRI, while any nucleus with a net nuclear spin can be used, the proton of the hydrogen atom remains the most widely used, especially in the clinical setting, because it is so ubiquitous and returns a large signal. This nucleus, present in water molecules, allows the excellent soft-tissue contrast achievable with MRI.

A number of different pulse sequences can be used for specific MRI diagnostic imaging (multiparametric MRI or mpMRI). It is possible to differentiate tissue characteristics by combining two or more of the following imaging sequences, depending on the information being sought: T1-weighted (T1-MRI), T2-weighted (T2-MRI), diffusion weighted imaging (DWI-MRI), dynamic contrast enhancement (DCE-MRI), and spectroscopy (MRI-S). For example, imaging of prostate tumors is better accomplished using T2-MRI and DWI-MRI than T2-weighted imaging alone.[5] The number of applications of mpMRI for detecting disease in various organs continues to expand, including liver studies, breast tumors, pancreatic tumors, and assessing the effects of vascular disruption agents on cancer tumors.[6][7][8]

Nuclear medicine encompasses both diagnostic imaging and treatment of disease, and may also be referred to as molecular medicine or molecular imaging & therapeutics.[9] Nuclear medicine uses certain properties of isotopes and the energetic particles emitted from radioactive material to diagnose or treat various pathology. Different from the typical concept of anatomic radiology, nuclear medicine enables assessment of physiology. This function-based approach to medical evaluation has useful applications in most subspecialties, notably oncology, neurology, and cardiology. Gamma cameras and PET scanners are used in e.g. scintigraphy, SPECT and PET to detect regions of biologic activity that may be associated with disease. Relatively short lived isotope, such as 99mTc is administered to the patient. Isotopes are often preferentially absorbed by biologically active tissue in the body, and can be used to identify tumors or fracture points in bone. Images are acquired after collimated photons are detected by a crystal that gives off a light signal, which is in turn amplified and converted into count data.

Fiduciary markers are used in a wide range of medical imaging applications. Images of the same subject produced with two different imaging systems may be correlated (called image registration) by placing a fiduciary marker in the area imaged by both systems. In this case, a marker which is visible in the images produced by both imaging modalities must be used. By this method, functional information from SPECT or positron emission tomography can be related to anatomical information provided by magnetic resonance imaging (MRI).[12] Similarly, fiducial points established during MRI can be correlated with brain images generated by magnetoencephalography to localize the source of brain activity.

Medical ultrasonography uses high frequency broadband sound waves in the megahertz range that are reflected by tissue to varying degrees to produce (up to 3D) images. This is commonly associated with imaging the fetus in pregnant women. Uses of ultrasound are much broader, however. Other important uses include imaging the abdominal organs, heart, breast, muscles, tendons, arteries and veins. While it may provide less anatomical detail than techniques such as CT or MRI, it has several advantages which make it ideal in numerous situations, in particular that it studies the function of moving structures in real-time, emits no ionizing radiation, and contains speckle that can be used in elastography. Ultrasound is also used as a popular research tool for capturing raw data, that can be made available through an ultrasound research interface, for the purpose of tissue characterization and implementation of new image processing techniques. The concepts of ultrasound differ from other medical imaging modalities in the fact that it is operated by the transmission and receipt of sound waves. The high frequency sound waves are sent into the tissue and depending on the composition of the different tissues; the signal will be attenuated and returned at separate intervals. A path of reflected sound waves in a multilayered structure can be defined by an input acoustic impedance (ultrasound sound wave) and the Reflection and transmission coefficients of the relative structures.[11] It is very safe to use and does not appear to cause any adverse effects. It is also relatively inexpensive and quick to perform. Ultrasound scanners can be taken to critically ill patients in intensive care units, avoiding the danger caused while moving the patient to the radiology department. The real time moving image obtained can be used to guide drainage and biopsy procedures. Doppler capabilities on modern scanners allow the blood flow in arteries and veins to be assessed.

Elastography is a relatively new imaging modality that maps the elastic properties of soft tissue. This modality emerged in the last two decades. Elastography is useful in medical diagnoses, as elasticity can discern healthy from unhealthy tissue for specific organs/growths. For example, cancerous tumours will often be harder than the surrounding tissue, and diseased livers are stiffer than healthy ones.[13][14][15][16] There are a several elastographic techniques based on the use of ultrasound, magnetic resonance imaging and tactile imaging. The wide clinical use of ultrasound elastography is a result of the implementation of technology in clinical ultrasound machines. Main branches of ultrasound elastography include Quasistatic Elastography/Strain Imaging, Shear Wave Elasticity Imaging (SWEI), Acoustic Radiation Force Impulse imaging (ARFI), Supersonic Shear Imaging (SSI), and Transient Elastography.[14] In the last decade a steady increase of activities in the field of elastography is observed demonstrating successful application of the technology in various areas of medical diagnostics and treatment monitoring.

Tactile imaging is a medical imaging modality that translates the sense of touch into a digital image. The tactile image is a function of P(x,y,z), where P is the pressure on soft tissue surface under applied deformation and x,y,z are coordinates where pressure P was measured. Tactile imaging closely mimics manual palpation, since the probe of the device with a pressure sensor array mounted on its face acts similar to human fingers during clinical examination, slightly deforming soft tissue by the probe and detecting resulting changes in the pressure pattern. Figure on the right presents an experiment on a composite tissue phantom examined by a tactile imaging probe illustrating the ability of tactile imaging to visualize in 3D the structure of the object.

This modality is used for imaging of the prostate,[17] breast,[18]vagina and pelvic floor support structures,[19] and myofascial trigger points in muscle.[20]

Photoacoustic imaging is a recently developed hybrid biomedical imaging modality based on the photoacoustic effect. It combines the advantages of optical absorption contrast with ultrasonic spatial resolution for deep imaging in (optical) diffusive or quasi-diffusive regime. Recent studies have shown that photoacoustic imaging can be used in vivo for tumor angiogenesis monitoring, blood oxygenation mapping, functional brain imaging, and skin melanoma detection, etc.

Tomography is the imaging by sections or sectioning. The main such methods in medical imaging are:

When ultrasound is used to image the heart it is referred to as an echocardiogram. Echocardiography allows detailed structures of the heart, including chamber size, heart function, the valves of the heart, as well as the pericardium (the sac around the heart) to be seen. Echocardiography uses 2D, 3D, and Doppler imaging to create pictures of the heart and visualize the blood flowing through each of the four heart valves. Echocardiography is widely used in an array of patients ranging from those experiencing symptoms, such as shortness of breath or chest pain, to those undergoing cancer treatments. Transthoracic ultrasound has been proven to be safe for patients of all ages, from infants to the elderly, without risk of harmful side effects or radiation, differentiating it from other imaging modalities. Echocardiography is one of the most commonly used imaging modalities in the world due to its portability and use in a variety of applications. In emergency situations, echocardiography is quick, easily accessible, and able to be performed at the bedside, making it the modality of choice for many physicians.

FNIR Is a relatively new non-invasive imaging technique. NIRS (near infrared spectroscopy) is used for the purpose of functional neuroimaging and has been widely accepted as a brain imaging technique.[21]

Using superparamagnetic iron oxide nanoparticles, magnetic particle imaging (MPI) is a developing diagnostic imaging technique used for tracking superparamagnetic iron oxide nanoparticles. The primary advantage is the high sensitivity and specificity, along with the lack of signal decrease with tissue depth. MPI has been used in medical research to image cardiovascular performance, neuroperfusion, and cell tracking.

In response to increased concern by the public over radiation doses and the ongoing progress of best practices, The Alliance for Radiation Safety in Pediatric Imaging was formed within the Society for Pediatric Radiology. In concert with The American Society of Radiologic Technologists, The American College of Radiology and The American Association of Physicists in Medicine, the Society for Pediatric Radiology developed and launched the Image Gently Campaign which is designed to maintain high quality imaging studies while using the lowest doses and best radiation safety practices available on pediatric patients.[22] This initiative has been endorsed and applied by a growing list of various Professional Medical organizations around the world and has received support and assistance from companies that manufacture equipment used in Radiology.

Following upon the success of the Image Gently campaign, the American College of Radiology, the Radiological Society of North America, the American Association of Physicists in Medicine and the American Society of Radiologic Technologists have launched a similar campaign to address this issue in the adult population called Image Wisely.[23] The World Health Organization and International Atomic Energy Agency (IAEA) of the United Nations have also been working in this area and have ongoing projects designed to broaden best practices and lower patient radiation dose.[24][25][26]

Medical imaging may be indicated in pregnancy because of pregnancy complications, intercurrent diseases or routine prenatal care. Magnetic resonance imaging (MRI) without MRI contrast agents as well as obstetric ultrasonography are not associated with any risk for the mother or the fetus, and are the imaging techniques of choice for pregnant women.[27]Projectional radiography, X-ray computed tomography and nuclear medicine imaging result some degree of ionizing radiation exposure, but have with a few exceptions much lower absorbed doses than what are associated with fetal harm.[27] At higher dosages, effects can include miscarriage, birth defects and intellectual disability.[27]

The amount of data obtained in a single MR or CT scan is very extensive. Some of the data that radiologists discard could save patients time and money, while reducing their exposure to radiation and risk of complications from invasive procedures.[28] Another approach for making the procedures more efficient is based on utilizing additional constraints, e.g., in some medical imaging modalities one can improve the efficiency of the data acquisition by taking into account the fact the reconstructed density is positive.[29]

Volume rendering techniques have been developed to enable CT, MRI and ultrasound scanning software to produce 3D images for the physician.[30] Traditionally CT and MRI scans produced 2D static output on film. To produce 3D images, many scans are made, then combined by computers to produce a 3D model, which can then be manipulated by the physician. 3D ultrasounds are produced using a somewhat similar technique. In diagnosing disease of the viscera of abdomen, ultrasound is particularly sensitive on imaging of biliary tract, urinary tract and female reproductive organs (ovary, fallopian tubes). As for example, diagnosis of gall stone by dilatation of common bile duct and stone in common bile duct. With the ability to visualize important structures in great detail, 3D visualization methods are a valuable resource for the diagnosis and surgical treatment of many pathologies. It was a key resource for the famous, but ultimately unsuccessful attempt by Singaporean surgeons to separate Iranian twins Ladan and Laleh Bijani in 2003. The 3D equipment was used previously for similar operations with great success.

Other proposed or developed techniques include:

Some of these techniques[examples needed] are still at a research stage and not yet used in clinical routines.

Neuroimaging has also been used in experimental circumstances to allow people (especially disabled persons) to control outside devices, acting as a brain computer interface.

Many medical imaging software applications (3DSlicer, ImageJ, MIPAV, ImageVis3D, etc.) are used for non-diagnostic imaging, specifically because they dont have an FDA approval[31] and not allowed to use in clinical research for patient diagnosis.[32] Note that many clinical research studies are not designed for patient diagnosis anyway.[33]

Used primarily in ultrasound imaging, capturing the image produced by a medical imaging device is required for archiving and telemedicine applications. In most scenarios, a frame grabber is used in order to capture the video signal from the medical device and relay it to a computer for further processing and operations.[34]

The Digital Imaging and Communication in Medicine (DICOM) Standard is used globally to store, exchange, and transmit medical images. The DICOM Standard incorporates protocols for imaging techniques such as radiography, computed tomography (CT), magnetic resonance imaging (MRI), ultrasonography, and radiation therapy.[35] DICOM includes standards for image exchange (e.g., via portable media such as DVDs), image compression, 3-D visualization, image presentation, and results reporting.[36]

Medical imaging techniques produce very large amounts of data, especially from CT, MRI and PET modalities. As a result, storage and communications of electronic image data are prohibitive without the use of compression. JPEG 2000 is the state-of-the-art image compression DICOM standard for storage and transmission of medical images. The cost and feasibility of accessing large image data sets over low or various bandwidths are further addressed by use of another DICOM standard, called JPIP, to enable efficient streaming of the JPEG 2000 compressed image data.

There has been growing trend to migrate from PACS to a Cloud Based RIS. A recent article by Applied Radiology said, As the digital-imaging realm is embraced across the healthcare enterprise, the swift transition from terabytes to petabytes of data has put radiology on the brink of information overload. Cloud computing offers the imaging department of the future the tools to manage data much more intelligently.[37]

Medical imaging has become a major tool in clinical trials since it enables rapid diagnosis with visualization and quantitative assessment.

A typical clinical trial goes through multiple phases and can take up to eight years. Clinical endpoints or outcomes are used to determine whether the therapy is safe and effective. Once a patient reaches the endpoint, he or she is generally excluded from further experimental interaction. Trials that rely solely on clinical endpoints are very costly as they have long durations and tend to need large numbers of patients.

In contrast to clinical endpoints, surrogate endpoints have been shown to cut down the time required to confirm whether a drug has clinical benefits. Imaging biomarkers (a characteristic that is objectively measured by an imaging technique, which is used as an indicator of pharmacological response to a therapy) and surrogate endpoints have shown to facilitate the use of small group sizes, obtaining quick results with good statistical power.[38]

Imaging is able to reveal subtle change that is indicative of the progression of therapy that may be missed out by more subjective, traditional approaches. Statistical bias is reduced as the findings are evaluated without any direct patient contact.

Imaging techniques such as positron emission tomography (PET) and magnetic resonance imaging (MRI) are routinely used in oncology and neuroscience areas,.[39][40][41][42] For example, measurement of tumour shrinkage is a commonly used surrogate endpoint in solid tumour response evaluation. This allows for faster and more objective assessment of the effects of anticancer drugs. In Alzheimers disease, MRI scans of the entire brain can accurately assess the rate of hippocampal atrophy, while PET scans can measure the brains metabolic activity by measuring regional glucose metabolism,[38] and beta-amyloid plaques using tracers such as Pittsburgh compound B (PiB). Historically less use has been made of quantitative medical imaging in other areas of drug development although interest is growing.[43]

An imaging-based trial will usually be made up of three components:

Lead is the main material used for radiographic shielding against scattered X-rays.

In magnetic resonance imaging, there is MRI RF shielding as well as magnetic shielding to prevent external disturbance of image quality.

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Using donor stem cells to treat spinal cord injury

By Sykes24Tracey

Human neural stem cells are derived via fluorescence-activated cell sorting (FACS) from donated fetal brain tissue. Credit: Hal X. Nguyen and Aileen J. Anderson

A new study in mice published in The Journal of Neuroscience details a potential therapeutic strategy that uses stem cells to promote recovery of motor activity after spinal cord injury.

The transplantation of neural stem cells could help promote repair of an injured spinal cord, but the interaction between donor cells and the resident cells that are part of the body's immune response to injury is not well understood.

Hal Nguyen, Aileen Anderson and colleagues found that mice receiving stem cells derived from donated human brain tissue required depletion of a specific population of immune cells in order to improve the mice's ability to walk along a glass plate. Although the donor cells survived equally when transplanted immediately or 30 days after injury, their location and cell type changed with time. These results suggest that immune cells populating the spinal cord at different time points after injury affect the ability of stem cells to promote functional recovery.

Human neural stem cell replicates itself during mitosis in vitro. Credit: Hal X. Nguyen and Aileen J. Anderson

Explore further: Stem cell scarring aids recovery from spinal cord injury

More information: "Systemic neutrophil depletion modulates the migration and fate of transplanted human neural stem cells to rescue functional repair," Journal of Neuroscience (2017). DOI: 10.1523/JNEUROSCI.2785-16.2017

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This Week In Neuroscience News 8/31/17 – ReliaWire

By Sykes24Tracey

This weeks roundup of recent developments in neuroscience kicks off with a study from MIT, where engineers have devised a way to automate the process of monitoring neurons in a living brain using a computer algorithm that analyzes microscope images and guides a robotic arm to the target cell. In the above image, a pipette guided by a robotic arm approaches a neuron identified with a fluorescent stain.

Neurosurgeons at the Center for iPS Cell Research and Application, Kyoto University. They report two new ways to improve outcomes of induced pluropontent stem cell-based therapies for Parkinsons disease in monkey brains. The findings are a key step for patient recruitment of the first iPS cell-based therapy to treat neurodegenerative diseases, since one of the last steps before treating patients with an experimental cell therapy for the brain is confirmation that the therapy works in monkeys.

In other Parkinsons news, the FDA has denied Acorda Therapeutics New Drug Application filing for Inbrija. Inbrija is an inhaled, self-administered, form of levodopa for treating Parkinsons disease. According to the FDA, reason for the denial were the date when the manufacturing site would be ready for inspection, and a question regarding submission of the drug master production record. FDA also requested additional information at resubmission, which was not part of the basis for the refusal.

At the University of Turku, in Finland, researchers have revealed how eating stimulates the brains endogenous opioid system to signal pleasure and satiety. Interestingly, eating both bland and delicious meals triggered significant opioid release in the brain.

A young New York woman with severe headaches represented a never-before-seen case for neurosurgeons at New York Presbyterian. She was diagnosed with an unusual form of hydrocephalus/Chiari malformation, in which the skull is too small and restricted the brain. More about her in the video below:

Tinnitus, a chronic ringing or buzzing in the ears, has eluded medical treatment and scientific understanding. A new University of Illinois at Urbana-Champaign study found that chronic tinnitus is associated with changes in certain networks in the brain, and furthermore, those changes cause the brain to stay more at attention and less at rest. The finding provides patients with validation of their experiences and hope for future treatment options.

In social media news, research by BuzzFeed found more than half of the most-shared scientific stories about autism published in the last five years promote unevidenced or disproven treatments, or purported causes. More disturbingly, families in the autism community are excessively targeted by purveyors of bad information, making them more vulnerable to harmful, unproven so-called treatments.

Top Image: Ho-Jun Suk

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Somatic SNAFUCan a Few Mutant Microglia Cause Neurodegenerative Disease? – Alzforum

By Sykes24Tracey

01 Sep 2017

A paper in the September 1 Nature claims a cadre of rogue microglia are all it takes to orchestrate neurodegeneration. Researchers led by Frederic Geissmann and Omar Abdel-Wahab of Memorial Sloan Kettering Cancer Center in New York, and Marco Prinz of the University of Freiburg in Germany, induced a somatic mutation in about 10 percent of microglia that switched on ERK kinase signaling. The mice later developed a severe neurodegenerative disease that paralyzed them. The researchers determined that damaging inflammation caused by the mutated microglia was likely to blame. The findings raise the possibility that similar somatic mutations in people are responsible for a rare neurodegenerative disease that occurs inchildren.

This is a great paper for many reasons, commented Bart De Strooper of the Dementia Research Institute in the U.K. I am particularly excited about the concept of acquired genetic mosaicism as a cause of neurodegenerative disorder. The paper also shows that microglia mutations can be directly causative inneurodegeneration.

Most famous for their role in causing cancer, somatic mutations can spontaneously arise in any cell, sometimes giving it a proliferative edge. Mutations in the RAS-MEK-ERK signaling pathway, for example, can cause diseases called histiocytoses if they arise in the myeloid cell lineage, which gives rise to blood and immune cells, including macrophages and microglia. Histiocytoses manifest in different ways, including leukemias, other tumors, and malfunctions in multiple organs. Mysteriously, a small fraction of carriers also get a neurodegenerative disease that manifests between childhood and middle age, with symptoms such as cerebellar ataxia and tremor (Lachenal et al., 2006; Wnorowski et al., 2008). The reason for the neurodegeneration has been amystery.

Geissmann and colleagues speculated it could be caused by microglia descended from erythro-myeloid progenitor cells (EMPs) harboring the same RAS-MEK-ERK somatic mutations. EMPs arise in the embryonic yolk sac early in development, and give rise to microglia in the brain and macrophages in other tissues (Perdiguero et al., 2014; Feb 2015 conference news).In contrast, circulating monocytes are continually replenished by hemotopoietic stem cells (HSCs) in the bonemarrow.

Doomed During Development? Histiocytoses arise from somatic mutations in hematopoietic stem cells (HSCs, left) or in erythro-myeloid progenitor (EMP) cells (right), which give rise to macrophages and microglia. The mutant microglia may cause inflammation, leading to neurodegeneration. [Courtesy of Tarnawsky and Yoder, Nature, News & Views,2017.]

To find out if somatic mutations in EMPs could beget microglia that trigger neurodegeneration, first author Elvira Mass and colleagues induced a somatic mutation that causes histiocytoses into mice. They chose the V600E variant of the BRAF gene, a substitution that switches on ERK signaling. The researchers generated transgenic mice carrying an inducible copy of the mutated BRAF gene, which could only be switched on via tamoxifen-induced Cre recombination in EMPs. This also turned on yellow fluorescent protein so the researchers could identify the cells. At embryonic day 8.5, they injected pregnant mice with a teeny dose of the drug to ensure that only a fraction of the embryos EMPs would express the mutation. About 10 percent of tissue resident macrophages, including microglia, in the resulting offspring expressed V600E BRAF at one month ofage.

The mutant microglia took up their positions in the brain, but were different from their normal counterparts from the get-go. Those carrying the V600E BRAF expressed elevated markers of proliferation, ERK signaling, and inflammation. In one-month-old mice, these feisty microglia had yet to cause trouble, but by four months of age, the researchers noticed neurological symptoms in the mice, including loss of hind limb reflexes and shortened stride. At seven months, 90 percent of the animals were affected and by nine months 60 percent of the mice had full hind limb paralysis. These symptoms, similar to cerebellar ataxia, are common in people with cerebral histiocytoses. Feeding the mice a BRAF inhibitor starting at one month of age drastically delayed onset and slowedprogression.

Compared to wild-type mice (left), animals with induced BRAF mutations in their EMPs had an expansion of mutant microglia expressing YFP in their spinal cord (middle). Microglia also expressed the activation marker CD68 (top) and phosphorylated ERK (bottom). [Courtesy of Mass et al., Nature2017.]

The researchers next searched for pathological changes that could have triggered the disorder. In month-old mice, the researchers found signs of elevated microglial and astrocyte activation, but not neuronal death. Oddly, by immunohistochemistry using the 22C11 antibody, the researchers noticed deposits of amyloid precursor protein (APP) in the inflamed areas, a phenomenon that Geissmann attributed to release of the membrane protein from newly damaged axons. In six-month-old animals, large clusters of activated, phagocytic microglia carrying the BRAF mutation crowded in the thalamus, brain stem, cerebellum, and spinal cord. These same regions were rife with synaptic and neuronal loss, demyelination, and astrogliosis. The mutant microglia had a small proliferative advantage compared with their wild-type counterparts, but Geissmann attributed the bulk of the neuronal damage to the activation of the cells, rather than their expansion. Treatment with a BRAF inhibitor mitigated theseresponses.

Gene expression analysis of mutant microglia taken from paralyzed mice revealed the differential expression of around 8,000 genes, 80 percent of which were upregulated compared to microglia from control mice. These genes included a bevy of pro-inflammatory mediators, including cytokines, phagocytosis boosters, matrix proteins, and growthfactors.

For some reason, the thalamus, brain stem, cerebellum, and spinal cord were uniquely vulnerable to the presence of the V600E BRAF mutant cells. Tissue macrophages carrying the mutation also expanded in the liver, spleen, kidney, and lung, even more so than in the brain, but did not cause damage in those regions. Geissmann speculated that differences in the tissue microenvironment could play a role in this selective vulnerability. For example, normal liver macrophages are in a near constant state of activation, Geissmann said, so the organ is equipped to deal with them. Perhaps the posterior part of the brain is unaccustomed to constant microglial activation, he said. Indeed, chronic microglial activation occurs during AD as well, and appears to ultimately inflict damage, rather than helpfulresponses.

Finally, the researchers investigated whether patients with histiocytoses also had abnormal microglia. They analyzed postmortem brain tissue from three patients with Erdheim-Chester disease (ECD), and conducted gene expression analysis on brain biopsies from one person with Langerhans cell histiocytosis (LCH), and another with juvenile xanthogranuloma (JXG). All of these patients had neurodegenerative disease associated with their histiocytoses, which were all caused by BRAF V600E mutations. In the ECD samples, the researchers spotted abundant activated microglia gathered at sites of neuronal loss, astrogliosis, and demyelination. Compared with data from five control samples, gene expression analysis on the JXG and LCH samples revealed an upregulation of genes in the MAPK pathway, including multiple pro-inflammatorycytokines.

The findings support the idea that activated microglia wreak havoc in the brain and cause neurodegeneration in people withhistiocytoses.

For a somatic mutation to have an effect, affected cells must propagate sufficiently. EMPs proliferate during early development, making it a prime time for mutant clones to multiply, Geissmann said. Perhaps the number of mutant clones born during the EMP stage would suffice to harm neurons, he said. However, if microglia are also bestowed with a proliferative edge, this would likely exacerbate the damage, he added. Either way, Geissmann proposed that inhibitors of ERK signaling might thwart neurodegeneration when mutant microglia areinvolved.

In an accompanying editorial, Stefan Tarnawsky and Mervin Yoder at Indiana University in Indianapolis noted opportunities for better diagnosis in this scenario. When somatic mutations occur in EMPs during early development, macrophages in many regions of the body will likely carry the mutations, not just microglia in the brain. This suggests that it might be possible to collect macrophage samples from more easily accessible, non-CNS tissues to look for biomarkers when diagnosing microglia-related disease, theywrote.

What about somatic mutations that might arise later in life, when tissue resident macrophages or microglia are already nestled into their permanent residences? Though recent studies reported that microglia are relatively long-lived cells, they proliferate in response to threats (Aug 2017 news),perhaps setting the stage for expansion of mutant cells, Geissmann speculated. That said, beyond people with histiocytoses, the contribution of somatic mutations in microglia to neurodegenerative disease is unclear. De Strooper and others have reported that genetic mosaicism in neurons could cause neurodegeneration (Jul 2015 news). A major impediment to studying this phenomenon is that somatic mutations that arise in the brain go undetected in standard genomic sequencing.JessicaShugart

No Available Further Reading

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FDA cracks down on bogus cell therapy firms – pharmaphorum

By Sykes24Tracey

The FDAs commissioner Scott Gottlieb has pledged to crack down on unscrupulous actors attempting to treat patients with potentially dangerous or unproven stem cell therapies.

According to Gottlieb, these companies are able to promote, unproven, illegal and expensive treatments that offer little hope and could pose health risks to vulnerable patients, based on the clinical promise of regenerative medicine.

The crackdown comes after a number of shocking incidents in the US, including the case of three women who went blind following bogus treatment at a Florida clinic.

In a statement the FDA said it is stepping up enforcement to separate unscrupulous companies from those offering genuine treatments approved and backed with genuine medical evidence.

At the same time it will offer those with regenerative medicine products a less burdensome regulatory process although the regulator noted that in some cases individualised treatments fall outside the FDAs remit.

Gottlieb noted the FDA must tread a fine line, separating new medical products from those that are tailor-made by surgeons in such a way that they are not subject to its regulation.

The announcement comes after the US Marshals Service, on behalf of the FDA seized five vials of smallpox vaccine from California-based StemImmune.

The San Diego biotech was using the vaccinia virus vaccine to create an unapproved stem cell product, from cells derived from body fat.

This was being injected intravenously and directly into patients tumours potentially causing fatal health problems in unvaccinated people as the virus can cause inflammation and swelling of the heart.

The FDA also wrote to another operator, Floridas Stem Cell Clinic, raising issues about poor manufacturing standards. An inspection found the clinic was processing body fat into stem cells and administering directly into spinal cords of patients with illnesses such as Parkinsons disease, amyotrophic lateral sclerosis, and pulmonary fibrosis.

This autumn, Gottlieb said he will issue guidance documents outlining a new, efficient, process to evaluate safety and effectiveness of stem cell therapies.

The guidance will also implement provisions of the 21st Century Cures Act relating to regenerative medicine.

A compliance policy will give current product developers a very reasonable grace period to consult with the FDA so that they can meet required standards aside from outliers potentially harming public health.

Gottlieb said: We cant let a small number of unscrupulous actors poison the well for the good science that holds the promise of changing the contours of human illness and altering the trajectory of medicine and science.

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Center for Embryonic Cell and Gene Therapy | Center for …

By Sykes24Tracey

Mitalipov successfully repairs genes in human embryos

A ground breaking discovery by Shoukhrat Mitalipov, Ph.D.,was reported in Nature the successful removal of a lethal geneticdefect in human embryos. The breakthrough is the initial confirmation that adangerous genetic defect can in theory be erased.

Scientific success in embryo editing re-opens reg debate. BioWorld

Study in Nature demonstrates method for repairing genes in human embryos that prevents inherited diseases. OHSU News

Gene Editing Breakthrough. Charlie Rose Show

A Promising And Still Uncertain Future For Human Gene Editing. Science Friday

In Breakthrough, Scientists Edit a Dangerous Mutation From Genes in Human Embryos. NY Times

First human embryo editing experiment in U.S.'corrects' gene for heart condition. The Washington Post.

Scientists Precisely Edit DNA In Human Embryos To Fix A Disease Gene. NPR

Human embryos edited to stop disease. BBC

A Gene Editing Breakthrough. On Point with Tom Ashbrook.

First U.S.-based group to edit human embryos brings practice closer to clinic. Science

In breakthrough, OHSU corrects defective gene in embryo. Oregonlive.

First Safe Repair of Gene in Human Embryos. Associated Press.

A new discovery may unlock the answer to a vexing scientificquestion: How to conduct mitochondrial replacement therapy, a new gene-therapytechnique, in such a way that safely prevents the transmission of harmful mitochondrialgene mutations from mothers to their children.

For women with mitochondrial diseases, a step closer to preventing transmission. STAT

Human embryo experiment shows progress toward 'three-parent' babies. The Washington Post

Families struggling with infertility or a genetic predisposition for debilitating mitochondrial diseases may someday benefit from a new breakthrough led by scientists at OHSU and the Salk Institute for Biological Studies.

Egg 'nobbles' can be used to create embryos, say scientists in fertility breakthrough

Fertility success may get boost from new research

First he pioneered a new way of making life. Now he wants to try it in people

Shoukhrat Mitalipov: The cloning chief.

Researchers announced they had derived stem cells fromcloned human embryos, a long-awaited research coup that Science's editors choseas a runner-up for Breakthrough of the Year.Read the article on Science

#4. Finally, We're Just Like Dolly

#5. Functioning Organs Made From Stem Cells

#2. Human embryonic stem cells cloned

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How your own stem cells could relieve your chronic pain – Good4Utah

By Sykes24Tracey

Dr. Khan from Wasatch Pain Solutions gave us insight to Regenexx, the world's most advanced stem cell and blood platelet procedures.

On what makesRegenexx treatments better than any other, Dr. Khan explained that a network of doctors and researchers have performed more stem cell related procedures than any other group in the United States; over 51,000 procedures. Which he says has lead them to producing over 50% of all available orthopedic stem cell research in the world.

Dr. Khan explained they only use a persons own living stem cells from their bone marrow along with their own blood platelets during their patented 3-step process. Studies show that bone marrow stem cells are vastly superior for orthopedic applications like helping to regenerate cartilage and heal tissue damage. The outcome that their process produces can help patients avoid surgery and maintain a very active lifestyle without severe pain.

For more information visit wasatchpainsolutions.com or call (801) 302-2690.

This story includes sponsored content.

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Providing Leading-edge Cardiovascular Care – The Lane Report

By Sykes24Tracey

SPECIAL ADVERTISING REPORT

HOWEVER, THERE ARE OTHER components of KentuckyOne Health Heart and Vascular Care that make it the critical statewide resource it is today. Research, community outreach and support of advocacy organizations are all important aspects of our mission to be the states leader in cardiovascular care.

Innovative Care

KentuckyOne provides patients with a full spectrum of cardiovascular care, with treatments for common problems as well as complex cardiovascular conditions. Our surgeons, nursing staff and other health care professionals utilize the latest diagnostic and therapeutic techniques to treat any type of patient with any type of condition.

Whether youre in need of heart attack care; heart rhythm care for cardiac arrhythmia; transplant (Louisville only) or mechanical device care for advanced heart failure; minimally invasive treatment for a disease like aortic stenosis or mitral regurgitation; vascular care for an aneurysm or artery disease; cardiac rehabilitation at one of our Healthy Lifestyle Centers; or some other type of heart and vascular service, KentuckyOne Health is the place to go.

Having access to the best equipment and newest treatments is only part of the equation, said Nezar Falluji, MD, MPH, interventional cardiologist with KentuckyOne Health Cardiology Associates and director of cardiovascular services for the KentuckyOne Health Lexington market at Saint Joseph Hospital. The teamwork and collaboration between cardiologists, cardiovascular surgeons, anesthesiologists, nurses and other staff and physicians is what sets us apart.

Groundbreaking Research

Through a partnership with the University of Louisville and its physicians, KentuckyOne Health, and specifically Jewish Hospital and University of Louisville Hospital, is the site for groundbreaking research across many disciplines. Jewish Hospital is the primary site in Louisville for cardiovascular research.

The University of Louisville offers access to academic research and innovation that may be effectively applied in clinical settings, said Mark Slaughter, MD, professor and chair of the Department of Cardiovascular and Thoracic Surgery at the University of Louisville and executive director of cardiovascular services for the KentuckyOne Health Louisville market. Through this research component, Jewish Hospital, the University of Louisville and KentuckyOne Health are leading the way in developing next-generation cardiovascular therapies.

Roberto Bolli, MD, chief of the Division of Cardiovascular Medicine at the University of Louisville, is a renowned researcher whose stem cell therapy work has garnered worldwide attention.

Dr. Bolli has become a world leader in using patients own stem cells, growing them in tissue culture and then infusing them back into the injured heart, as a way to repopulate the heart with cardiac cells that will grow and heal. He is doing truly leading-edge cardiac stem cell work right here in Kentucky.

Many of the vascular diseases are silent and often go unnoticed until they eventually lead to major problems, said Stephen Self, MD, vascular surgeon at KentuckyOne Health Vascular Surgery Associates. Its crucial that people are aware of the risk factors and become proactive about their health.

Knowing the Risk Factors

Despite the sly nature of many vascular diseases, there are some controllable and uncontrollable risk factors you should know about, including:

Age People 50 and older are at greatest risk.

Smoking Smoke inhalation increases vascular damage.

Lack of exercise Contributes to fat storage, muscle loss and low energy.

Obesity A common sign of poor vascular health

Unhealthy diet Poor diets can increase bad cholesterol levels and high blood pressure.

Genetics Your family medical history can help define your risk.

Protecting Yourself

I recommend people with increased risk of vascular disease, such as those who smoke or have high blood pressure or high cholesterol, and anyone over the age of 50, get vascular screenings, said Steve Lin, MD, who specializes in vein care at KentuckyOne Health Cardiology Associates. They are completely painless, inexpensive and can ultimately save your life.

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Struggling with a chronic or life-threatening illness? Your blood can help research cures – Sacramento Bee

By Sykes24Tracey

For anyone diagnosed with cancer, Alzheimers or AIDS, perhaps the best hope for finding cures lies in their own bodies more specifically, in the cells traveling through their blood.

Scientists at major universities and pharmaceutical companies need more of those cells to do their cutting-edge medical research, and Folsoms StemExpress is leading the way nationwide. Company CEO Cate Dyer is trying to get out the word to potential donors that their blood is essential to this work.

StemExpress collects blood, bone marrow, plasma or cord blood at its centers and compensates donors for their time and discomfort. Then it processes their samples into a range of products, including many of the cells on your bodys healing team: white blood cells, stem cells, T cells and others that answer the call when the body confronts a disease or disability.

We really want to get out to people in Sacramento and the region that we need diseased donors at our sites, and thats everyone people who have an early-diagnosed cancer, people in treatment, theyre having radiation post-treatment and remission, from everything like AML, leukemia, lymphoma, all of the major cancer space, said Cate Dyer, the companys founder and CEO. But also, we have AIDS projects going on right now where we need AIDS-positive samples.

Its not just cancer or AIDS, though. Some researchers also use cells from the samples to study chronic diseases such as diabetes and high blood pressure or to study illnesses that have no cures such as Alzheimers or Parkinsons.

Researchers can take many paths when studying cells from different people, at different stages of a disease, said Dr. Michael Chez, a pediatric neurologist with Sutter in the Sacramento region. For example, researchers could develop screenings for early detection of a disease or genetic defect, or duplicate defective tissues to see how to repair what went wrong. Their findings might help to develop drugs or chemicals that will help to reverse or change the course of a disease. Already, scientists have begun harvesting stem cells, turning them into specific tissues and using them for replacement or repair.

To help potential donors understand the impact they can have on research, Dyer highlighted the work that StemExpress started doing seven years ago with San Diego-based Sequenom, a life-sciences company that was attempting to develop a less-invasive way to check for genetic defects in fetuses. At the time, doctors were using a needle, pushing through the wall of the abdomen and into the uterus to collect and test elements of the amniotic fluid to assess genetic abnormalities.

It was a procedure that frightened women not only because of concerns about their unborn babies but also because they feared that they might be one of the small percentage of women who suffered a major complication as a result of the amniocentesis.

Sequenom envisioned a test that, by contrast, would simply examine blood drawn from the expectant mother. To develop the test, Sequenoms researchers would have to isolate and study DNA strands for both expectant moms and their fetuses. By studying DNA from thousands of donors, the life sciences company was able to identify DNA mutations, deletions and alterations and develop a way to check for them in the blood rather than in amniotic fluid.

At the time, when I met (Sequenoms senior director of clinical operations) they were sourcing about 25 (blood) samples a week, just to give you a ballpark, Dyer said, and I asked him, Well, how long is it going to take you to meet all the (Food and Drug Administration) requirements needed, sourcing 25 samples a week? And, he was like, Five to six years to get all our projects together.

Dyer made it her priority to significantly speed up that development timeline by delivering 300 samples a week, a feat she said the company accomplished within 90 days. Along the way, Stem Express became the largest global supplier of maternal blood for research purposes.

If it takes six years for them to source all the samples and another year and a half to get that through the FDA, youre looking at an eight-year turnaround just to get that ... to a patient, Dyer said. If we can shorten that, which we did, to almost a year and a half and get that then to the FDA and back out to patients, weve just massively impacted patient health care.

Chez talks regularly with patients or the parents of patients who are impatient for better treatments or cures, he said, but the availability of donor blood, cells and DNA already has sped up the pace of development of new drugs, screenings or treatments, and that pace should continue to improve as the bank of samples grows.

What also excites Chez is that multiple researchers can benefit from the millions of cells extracted from a blood draw from a single patient. Think of what this means, he said, for orphan diseases those conditions that affect fewer than 200,000 U.S. residents, such as Lou Gehrigs, cystic fibrosis or muscular dystrophy. A physician might run into a patient with one of these conditions once every 10 years, he said, but a few people living with these illnesses now have the power to provide cells to foster research around the world.

Experts then can study how a disease manifests at the cellular level, design methods of treatment and test them on human tissue in the lab, Chez said. There may not be enough patients in any one place to design treatment studies, he said, so human tissues can expand statistical ways to study the safety and efficacy of treatments.

One patient could help a disease study in multiple places versus just being limited to one researcher at one university, Chez said. If you have multiple people doing the work, it just amplifies how quickly things get done and the statistical power of that type of research. This is exponentially changing the algorithm of how research will be done in disease.

Dyer said she is often asked: Could giving blood pose a health risk for people struggling with cancer or other diseases? Her answer: It depends on the patient. StemExpress puts each donor through health assessments to determine how much blood they can give. Some patients may only be able to give one tablespoon; others, as much as six tablespoons.

Patients receive $25-$50 for blood draws, fees that are set by an independent review board. The company has collection centers at 2210 E. Bidwell St. in Folsom, another in Arlington, Mass., and is working to open another center in San Diego.

Researchers are typically specific about the kinds of diseased blood they need and even the stage or progression, Dyer said, so StemExpress is working to expand its donor database to ensure it has a variety of the cells needed.

Want to support biomedical research?

StemExpress is seeking people willing to give blood, white blood cells and bone marrow. The company accepts donations from patients who are healthy or those struggling with chronic or terminal illnesses.

The company compensates donors, based on the time they spend and the invasiveness of the procedure. People who give blood receive $25-50, for instance, while marrow donors receive $250.

A review board, independent of StemExpress, sets the payments. To learn more or to make an appointment, visit http://www.stemexpressdonors.com or call 1-877-900-7836.

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A Year Ago He Was Paralyzed From the Neck Down Then This Happened – Daily Reckoning

By Sykes24Tracey

You might feel a bit down if you watch the news. Who wouldnt?

Angry people might be grabbing headlines and making you wonder about the future, but the antidote is all around you.

Talk to some of your neighbors. Chances are, no matter what they look like or where theyre originally from, youll find theyre actually pretty decent people just like you.

The little improvements we all try to make may not register much, but the accumulation of them all eventually does.

And if theres one tangible piece of proof that the world is changing for the better, its Lucas Lindner.

2016 was not a kind year for 22-year-old Lucas.

Last May he lost control of his pickup truck when a deer ran out on the road. The front passenger tire blew out. The truck rolled, throwing him out of the window.

When he woke up in the hospital, he was paralyzed from the neck down. He was just heading to the grocery store on a Wisconsin Sunday morning.

It was an accident that could happen to anyone, to a friend or relative.

Normally, people like Lucas have no hope of restoring motor control of their bodies ever again.

In the United States, this awful story plays out 17,000 times every year. There are a quarter of a million people in the country with paralysis.

But Lucas story is working out a little bit differently.

Lucas was airlifted to Froedtert Hospital, a teaching hospital of the Medical College of Wisconsin.

There, Dr. Shekar N. Kurpad, professor of neurosurgery, applied 15 years of research into cell transplantation for spinal cord injury.

The procedure revolutionary and so were the cells Dr. Kurpad used.

The new procedure used cells that were developed over many years by researchers at a two companies leading the way in regenerative medicine.

Researchers at these companies have discovered how to grow stem cells and make them reliable for transplantation use.

On doctor, in fact, who Ive researched extensively, has been called the father of regenerative medicine.

Ive had the pleasure of meeting with him on a number of occasions.

Whenever I am in the San Francisco Bay Area, I try to visit him to learn whats going on in the field.

And from what Ive seen the therapeutic potential is hard to understate.

And were starting to see the results in people like Lucas Lindner.

Hes still wheelchair-bound we have a lot more to learn but he now has fine motor skills in his upper body. Thats extraordinary in cases like his.

Lucass miraculous improvement is due to newly designed pluripotent stem cells They are called pluripotent because they have the power to transform into any other cell type in the body.

And this Bay Area doctors company has accumulated the technology to make that happen.

Over the next few months, well get more clinical data from patients being treated with the full 20 million-cell dose and potentially more great news of restored motor function.

The recent headlines may have been about a few angry people rioting and hating each other, but the real important news is this

Recently, when the Cincinnati Reds played the Milwaukee Brewers, Lucas threw out the opening pitch.

Many U.S. presidents and other famous people have thrown pitches, but no pitch has been as historic as this one. And the advances I highlighted today are the reason why.

As this therapy matures and gets closer to market, I believe it will make a big impact on shares of companies in this space.

Which means the right-timed move in the upcoming months means a huge potential windfall of cash for you.

More to come soon.

For Tomorrows Trends Today,

Ray BlancoforThe Daily Reckoning

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Using stem cell patches to fix heart failure – Blasting News

By Sykes24Tracey

The pernicious effect of a heart attack includes the permanent damaging of heart muscles capacity to pump blood, causing healthy tissue to scar. People who suffer from this condition are often fatigued and cannot do as many things as they used to. They are also more prone to cardiac arrest, a condition that leads to death. Medication can help, and a heart transplant is sometimes used, though the necessity of using powerful anti-rejection drugs makes that option dangerous at the very least. The availability of donor hearts is also a limiting factor.

According to the CDC, 5.7 million Americans suffer from #Heart Failure.

Half of the people with the diagnosis die within five years. Heart failure costs the United States $30.7 billion a year in health care services, medication, and lost productivity.

A new option for people with this kind of heart failure is on the horizon, according to Mach. The idea is to grow patches of beating heart cells from a patients own tissue and then cover the parts of the heart that have been scarred by a cardiac event. The technology has the promise to allow heart failure patients to live nearly normal lives and to reduce the need for heart transplants.

Beating heart cell patches are created when blood cells are extracted from the patient and are transformed into stem cells using well known genetic engineering techniques. Then the stem cells would be used in a 3D printer to create living heart tissue, geared to match the exact size and shape of the area of the heart that has been scarred.

Then an open heart surgery procedure would be undertaken to implant the patch on the scarred tissue, including blood vessel grafts that would integrate the new tissue into the patients cardiovascular system.

The procedure would be a delicate one. The surgeon might cut the scarred tissue away and replace it with the patch or just overlay it with the theory that the scarring would go away in time. The hope is that the new tissue will beat in synchronicity with the rest of the heart.

The beauty of the procedure that even though it would cost $100,000, it will still be cheaper than a heart transplant, which costs $500,000 not including the expense of the anti-rejection drugs.

Researchers have enjoyed some success with the procedure in mice and pigs. The hope is that human trials can start in five years with the procedure being available in a clinical setting in about #Ten Years. #Stem Cell

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Bacterial infection stresses hematopoietic stem cells – Medical Xpress – Medical Xpress

By Sykes24Tracey

Bacterial infection activates hematopoietic stem cells in the bone marrow and significantly reduces the ability to produce blood through induced proliferation. Credit: Professor Hitoshi Takizawa

It has been thought that only immune cells would act as the line of defense during bacterial infection. However, recent research has revealed that hematopoietic stem cells, cells that create all other blood cells throughout an individual's lifetime, are also able to respond to the infection. A collaboration between researchers from Japan and Switzerland found that bacterial infection activates hematopoietic stem cells in the bone marrow and significantly reduces their ability to produce blood by forcibly inducing proliferation. These findings indicate that bacterial infections might trigger dysregulation of blood formation, such as that found in anemia or leukemia. This information is important to consider in the development of prevention methods for blood diseases.

Background: Bacterial Infection and the Associated Immune Reaction

When a person becomes infected with a virus or bacteria, immune cells in the blood or lymph react to the infection. Some of these immune cells use "sensors" on their surfaces, called Toll-like receptors (TLR), to distinguish invading pathogens from molecules that are expressed by the host. By doing so, they can attack and ultimately destroy pathogens thereby protecting the body without attacking host cells.

Bone marrow contains hematopoietic stem cells which create blood cells, such as lymphocytes and erythrocytes, throughout life. When infection occurs, a large number of immune cells are activated and consumed. It therefore becomes necessary to replenish these immune cells by increasing blood production in bone marrow. Recent studies have revealed that immune cells are not the only cells that detect the danger signals associated with infection. Hematopoietic stem cells also identify these signals and use them to adjust blood production. However, little was known about how hematopoietic stem cells respond to bacterial infection or how it affected their function.

Proof: Hematopoietic Stem Cell Response to Bacterial Infection

Researchers from Kumamoto University and the University of Zurich analyzed the role of TLRs in hematopoietic stem cells upon bacterial infection, given that both immune cells and hematopoietic stem cells have TLRs. Lipopolysaccharide (LPS), one of the key molecules found in the outer membrane of gram negative bacteria and known to cause sepsis, was given to laboratory animals to generate a bacterial infection model. Furthermore, researchers analyzed the detailed role of TLRs in hematopoietic stem cell regulation by combining genetically modified animals that do not have TLR and related molecules, or agents that inhibit these molecules.

The results showed that LPSs spread throughout the body with some eventually reaching the bone marrow. This stimulated the TLR of the hematopoietic stem cells and induced them to proliferate. They also discovered that while the stimulus promoted proliferation, it also induced stress on the stem cells at the same time. In other words, although hematopoietic stem cells proliferate temporarily upon TLR stimulation, their ability to successfully self-replicate decreases, resulting in diminished blood production. Similar results were obtained after infection with E. coli bacteria.

Future Work

This study reveals that hematopoietic stem cells, while not in charge of immune reactions, are able to respond to bacterial infections resulting in a reduced ability to produce blood. This suggests that cell division of hematopoietic stem cells forced by bacterial infection induces stress and may further cause dysregulated hematopoiesis like that which occurs in anemia or leukemia. "Fortunately we were able to confirm that this molecular reaction can be inhibited by drugs," said one of the study leaders, Professor Hitoshi Takizawa of Kumamoto University's IRCMS. "The medication maintains the production of blood and immune cells without weakening the immune reaction against pathogenic bacteria. It might be possible to simultaneously prevent blood diseases and many bacterial infections in the future."

This finding was posted online in Cell Stem Cell on 21 July 2017, and an illustration from the research content was chosen as the cover of the issue.

Explore further: Innate reaction of hematopoietic stem cells to severe infections

More information: Hitoshi Takizawa et al, Pathogen-Induced TLR4-TRIF Innate Immune Signaling in Hematopoietic Stem Cells Promotes Proliferation but Reduces Competitive Fitness, Cell Stem Cell (2017). DOI: 10.1016/j.stem.2017.06.013

Journal reference: Cell Stem Cell

Provided by: Kumamoto University

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Three Medical Spa Procedures to Reverse Your Summer Skin Damage – LaSalle News Tribune

By Sykes24Tracey

Soon we will be closing the pool, putting away the patio furniture, and getting jackets out of the closet. As summer comes to an end, our skin is usually in need of some tender loving care and it is a good time to think about repairing your summer skin damage.

Nicole Norris MD Medical Spa, in Peru, Illinois, provides medical-grade professional cosmetic treatments for the skin. We asked them to give their opinion on the top 3 procedures they do to reverse sun damage. Dr. NicoleNorris says Microneedling, Laser Photofacial and Chemical peels are by far the most effective ways to reverse damage from thermal energy safely and effectively.

We all know that UVA and UVB radiation from the sun is stronger in the summer, although it affects our skin all year long. This radiation produces free radicals in our skin and slows our skins ability to repair itself. When damage persists and the skin cannot keep up with the repair backlog, wrinkles, poor texture and skin laxity are formed. Microneedling, also referred to as collagen induction therapy, utilizes a device with multiple small needles which penetrate the skin, stimulating the skin to repair itself. Through these new open channels in the skin, products can also be introduced into the dermis without any barrier. Dr. Norris comments, At our office, we like to put hyaluronic acid, a building block of collagen, into the skin while the microneedling channels are still open. We are also seeing great results with a new product on the market that stimulates brand new skin stem cells. When we are born, a certain number of skin stem cells are activated that we use our whole lives to repair injured skin. These old stem cells get tired out, so activating new ones is really at the forefront of skin rejuvenation . Microneedling is done with topical numbing medicine making it very tolerable. There is some initial redness after the procedure but special make-up can be applied, if necessary, to cover it. Results are gradually seen over time as it takes our bodies about 3 to 6 months to make new collagen. The degree of skin damage determines how many treatments are needed.

When it heats up outside, we are not only exposed to UVA and UVB radiation that directly contributes to older looking skin, but also to heat. Heat stimulates our pigment cells which produce pigment or melanin. These pigment deposits create our tan, but also freckles, and worse yet, age spots. A laser treatment called Photofacial or Intense Pulse Light (IPL) is the most effective way to destroy pigment that has accumulated in the skin. The treatment is quick and feels like a few warm rubber band snaps. There is no downtime. In 7-14 days, you begin to see the pigment slough off. Depending how deep the pigment is deposited, determines how many IPL treatments you will need.

Medical-grade chemical peels are performed to treat unwanted pigment deposits in the skin as well as lines, skin texture and skin laxity. A combination of acids are applied to the skin for a brief period of time in multiple layers. The acids stimulate the skin to repair itself. A medium to deep chemical peel stimulates skin cell turnover which is important in treating aging skin. When we are 20 years old, our skin cell turnover to repair damaged skin is 10 days. Every 10 years, the time it takes to produce new skin goes up by 10 days. This is the physiologic reason that we gradually look older. Chemical peels decrease our time for new skin production resulting in reversal of facial aging states Tamara Smith, RN at Nicole Norris MD Medical Spa. Chemical peels are usually done in a series and are customized to each patient. If done correctly, chemical peels are not painful and you may experience a few days of mild flaking after the procedure.

I think many patients are fearful of these medical-grade skin rejuvenation procedures because of what they see on reality television and what they read on the internet. I encourage anyone interested in improving their appearance, repairing their summer sun damage, or deciding to not age gracefully to try these procedures under the supervision of a qualified physician, advises Dr. Norris. At Nicole Norris MD Medical Spa, they are offering a Flight of Medical Spa Procedures Package. This is a great way to rejuvenate your summer skin while sampling some new procedures. The flight includes 1 Microneedling procedure, 1 IPL Photofacial, and 1 Chemical Peel and is being offered for $300 off through September 30, 2017. Call 815-780-8264 for your appointment today. Mention Medical Spa Flight when you call. Procedures are typically done 3-4 weeks apart.

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Gene editing used to repair diseased genes in embryos – NHS Choices

By Sykes24Tracey

Deadly gene mutations removed from human embryos in landmark study, reports The Guardian. Researchers have used a gene-editing technique to repair faults in DNA that can cause an often-fatal heart condition called hypertrophic cardiomyopathy.

This inherited heart condition is caused by a genetic change (mutation) in one or more genes. Babies born with hypertrophic cardiomyopathy have diseased and stiff heart muscles, which can lead to sudden unexpected death in childhood and in young athletes.

In this latest study researchers used a technique called CRISPR-cas9 to target and then remove faulty genes. CRISPR-cas9 acts like a pair of molecular scissors, allowing scientists to cut out certain sections of DNA. The technique has attracted a great deal of excitement in the scientific community since it was released in 2014. But as yet, there have been no practical applications for human health.

The research is at an early stage and cannot legally be used as treatment to help families affected by hypertrophic cardiomyopathy. And none of the modified embryos were implanted in the womb.

While the technique showed a high degree of accuracy, its unclear whether it is safe enough to be developed as a treatment. The sperm used in the study came from just one man with faulty genes, so the study needs to be repeated using cells from other people, to be sure that the findings can be replicated.

Scientists say it is now important for society to start a discussion about the ethical and legal implications of the technology. It is currently against the law to implant genetically altered human embryos to create a pregnancy, although such embryos can be developed for research.

The study was carried out by researchers from Oregon Health and Science University and the Salk Institute for Biological Studies in the US, the Institute for Basic Science and Seoul University in Korea, and BGI-Shenzen and BGI-Quingdao in China. It was funded by Oregon Health and Science University, the Institute for Basic Science, the G. Harold and Leila Y. Mathers Charitable Foundation, the Moxie Foundation and the Leona M. and HarryB. Helmsley Charitable Trust and the Shenzhen Municipal Government of China. The study was published in the peer-reviewed journal Nature.

The Guardian carried a clear and accurate report of the study. While their reports were mostly accurate, ITV News, Sky News and The Independent over-stated the current stage of research, with Sky News and ITV News saying it could eradicate thousands of inherited conditions and the Independent claiming it opens the possibility for inherited diseases to be wiped out entirely. While this may be possible, we dont know whether other inherited diseases might be as easily targeted as this gene mutation.

Finally, the Daily Mail rolls out the arguably tired clich of the technique leading to designer babies, which seems irrelevant at this point. The CRISPR-cas9 technique is only in its infancy and (ethics aside) its simply not possible to use genetic editing to select desirable characteristics - most of which are not the result of one single, identifiable gene. No reputable scientist would attempt such a procedure.

This was a series of experiments carried out in laboratories, to test the effects of the CRISPR-Cas9 technique on human cells and embryos. This type of scientific research helps us understand more about genes and how they can be changed by technology. It doesnt tell us what the effects would be if this was used as a treatment.

Researchers carried out a series of experiments on human cells, using the CRISPR-cas9 technique first on modified skin cells, then on very early embryos, and then on eggs at the point of fertilisation by sperm. They used genetic sequencing and analysis to assess the effects of these different experiments on cells and how they developed, up to five days. They looked specifically to see what proportion of cells carrying faulty mutations could be repaired, whether the process caused other unwanted mutations, and whether the process repaired all cells in an embryo, or just some of them.

They used skin cells (which were modified into stem cells) and sperm from one man, who carried the MYBPC3 mutation in his genome, and donor eggs from women without the genetic mutation. This is the mutation known to cause hypertrophic cardiomyopathy.

Normally in such cases, roughly half the embryos would have the mutation and half would not, as theres a 50-50 chance of the embryo inheriting the male or female version of the gene.

The CRISPR-cas9 technique can be used to select and delete specific genes from a strand of DNA. When this happens, usually the cut ends of the strand join together, but this causes problems so cant be used in the treatment of humans. The scientists created a genetic template of the healthy version of the gene, which they introduced at the same time as using CRISPR-cas9 to cut the mutated gene. They hoped the DNA would repair itself with a healthy version of the gene.

One important problem with changing genetic material is the development of mosaic embryos, where some of the cells have corrected genetic material and others have the original faulty gene. If that happened, doctors would not be able to tell whether or not an embryo was healthy.

The scientists needed to test all the cells in the embryos produced in the experiment, to see whether all cells had the corrected gene or whether the technique had resulted in a mixture. They also did whole genome sequencing on some embryos, to test for unrelated genetic changes that might have been introduced accidentally during the process.

All embryos in the study were destroyed, in line with legislation about genetic research on embryos.

Researchers found that the technique worked on some of the stem cells and embryos, but worked best when used at the point of fertilisation of the egg. There were important differences between the way the repair worked on the stem cells and the egg.

Only 28% of the stem cells were affected by the CRISPR-cas9 technique. Of these, most repaired themselves by joining the ends together, and only 41% were repaired by using a corrected version of the gene.

67% of the embryos exposed to CRISPR-cas9 had only the correct version of the gene higher than the 50% that would have been expected had the technique not been used. 33% of embryos had the mutated version of the gene, either in some or all their cells.

Importantly, the embryos didnt seem to use the template injected into the zygote to carry out the repair, in the way the stem cells did. They used the female version of the healthy gene to carry out the repair, instead.

Of the embryos created using CRISPR-cas9 at the point of fertilisation, 72% had the correct version of the gene in all their cells, and 28% had the mutated version of the gene in all their cells. No embryos were mosaic a mixture of cells with different genomes.

The researchers found no evidence of mutations induced by the technique, when they examined the cells using a variety of techniques. However, they did find some evidence of gene deletions caused by DNA strands splicing (joining) themselves together without repairing the faulty gene.

The researchers say they have demonstrated how human embryos employ a different DNA damage repair system to adult stem cells, which can be used to repair breaks in DNA made using the CRISPR-cas9 gene-editing technique.

They say that targeted gene correction could potentially rescue a substantial portion of mutant human embryos, and increase the numbers available for transfer for couples using pre-implantation diagnosis during IVF treatment.

However, they caution that despite remarkable targeting efficiency, CRISPR-cas9-treated embryos would not currently be suitable for transfer. Genome editing approaches must be further optimised before clinical application can be considered, they say.

Currently, genetically-inherited conditions like hypertrophic cardiomyopathy cannot be cured, only managed to reduce the risk of sudden cardiac death. For couples where one partner carries the mutated gene, the only option to avoid passing it on to their children is pre-implantation genetic diagnosis. This involves using IVF to create embryos, then testing a cell of the embryo to see whether it carries the healthy or mutated version of the gene. Embryos with healthy versions of the gene are then selected for implantation in the womb.

Problems arise if too few or none of the embryos have the correct version of the gene. The researchers suggest their technique could be used to increase the numbers of suitable embryos. However, the research is still at an early stage and has not yet been shown to be safe or effective enough to be considered as a treatment.

The other major factor is ethics and the law. Some people worry that gene editing could lead to designer babies, where couples use the tool to select attributes like hair colour, or even intelligence. At present, gene editing could not do this. Most of our characteristics, especially something as complex as intelligence, are not the result of one single, identifiable gene, so could not be selected in this way. And its likely that, even if gene editing treatments became legally available, they would be restricted to medical conditions.

Designer babies aside, society needs to consider what is acceptable in terms of editing human genetic material in embryos. Some people think that this type of technique is "playing God" or is ethically unacceptable because it involves discarding embryos that carry faulty genes. Others think that its rational to use the scientific techniques we have developed to eliminate causes of suffering, such as inherited diseases.

This research shows that the questions of how we want to legislate for this type of technique are becoming pressing. While the technology is not there yet, it is advancing fast. This research shows just how close we are getting to making genetic editing of human embryos a reality.

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Are cardiac stem cells a ‘fountain of youth’? | Genetic Literacy Project – Genetic Literacy Project

By Sykes24Tracey

Cardiac stem cells derived from young hearts helped reverse the signs of aging when directly injected into the old hearts of elderly rats, astudypublished Monday in the European Heart Journal demonstrated.

The old rats appeared newly invigorated after receiving their injections. As hoped, the cardiac stem cells improved heart function yet also provided additional benefits. The rats fur, shaved for surgery, grew back more quickly than expected, and their chromosomal telomeres, which commonly shrink with age, lengthened.

Its extremely exciting, said Dr. Eduardo Marbn, primary investigator on the research and director of the Cedars-Sinai Heart Institute. Witnessing the systemic rejuvenating effects, he said, its kind of like an unexpected fountain of youth.

The working hypothesis is that the cells secrete exosomes, tiny vesicles that contain a lot of nucleic acids, things like RNA, that can change patterns of the way the tissue responds to injury and the way genes are expressed in the tissue, Marbn said.

It is the exosomes that act on the heart and make it better as well as mediating long-distance effects on exercise capacity and hair regrowth, he explained.

The GLP aggregated and excerpted this blog/article to reflect the diversity of news, opinion, and analysis. Read full, original post:Unexpected fountain of youth found in cardiac stem cells, says researcher

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Woman Will Use Stem Cells From Her Baby’s Umbilical Cord To Save Her Brother, Who Has a Brain Tumor – LifeNews.com

By Sykes24Tracey

A pregnant British mom hopes she and her unborn baby will be the answer to help prolong her ailing brothers life.

Georgina Russell, of Preston, England, said she was desperate to help her brother, Ashley, when doctors diagnosed him with a slow-growing but deadly brain tumor earlier this year, according to the Daily Mail.

Georgina said she began researching his condition, glioblastoma, online and looking for answers that could save his life. She found one: her pregnancy.

Stem cells produced in the umbilical cord between her and her unborn baby potentially could be used in a treatment to shrink Ashleys tumor, according to the report. Once Georgina gives birth, she said doctors will be able to harvest and store the stem cells until Ashley needs them.

There is no harm to the baby or the mother when doctors harvest stem cells from the umbilical cord unlike embryonic stem cells, which only can be taken by killing a human life in the embryonic stage.

Georgina told the Mail: The blood from the cord is being used in trials across the world. It can do amazing things to help the body repair itself. If we store the stem cells, they can be kept to be used throughout Ashleys treatment when he needs them.

They might be able to inject them into the spinal fluid, to shrink the tumour on the brain, or they may be able to use the tissue grown from them to repair any damage to other parts of his body, if he has to have chemotherapy or radiotherapy.

Ashley Russell, a British military veteran, husband and father, said doctors found the tumor after he began suffering from headaches, dizzy spells and mini-seizures about six months ago. Later, he said he also began having blurred vision. Doctors ran a series of tests before discovering the tumor on his brain.

He said doctors suggested surgery, but the procedure has high risks. They gave him about five years to live, according to the report.

Georgina said she was devastated for her brother and his family, and she began researching ways to help him. In her research online, she said she discovered how stem cells collected from the umbilical cord are helping to treat people with tumors and other diseases.

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Her brother said the idea seemed odd at first, but he is willing to try anything.

I am quite a positive person so although the diagnosis was difficult, I am determined to do whatever I can to keep going, Ashley said. I did think about not being around to see my little girl get married and knew that if there was anything that might help, I would give it a go.

Georgina currently is 33 weeks pregnant with her unborn child, the report states.

Stem cells are so powerful and his new niece or nephew could save his life, she said.

The family set up a JustGiving page to help pay for the storage of the stem cells and Ashleys treatment.

Adult stem cells and those from umbilical cords are proving to be live-saving, while life-destroying embryonic stem cells have not been effective.

David Prentice, vice president and research director for the Charlotte Lozier Institute, explained more about the effectiveness of these life-saving stem cells in 2014:

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Umbilical cord blood stem cells have become an extremely valuable alternative to bone marrow adult stem cell transplants, ever since cord blood stem cells were first used for patients over 25 years ago. The first umbilical cord blood stem cell transplant was performed in October 1988, for a 5-year-old child with Fanconi anemia, a serious condition where the bone marrow fails to make blood cells. That patient is currently alive and healthy, 25 years after the cord blood stem cell transplant.

Prentice said more than 30,000 cord blood stem cell transplants have been done across the world. These stem cells have helped treat people with blood and bone marrow diseases, leukemia and genetic enzyme diseases, he said.

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Woman Will Use Stem Cells From Her Baby's Umbilical Cord To Save Her Brother, Who Has a Brain Tumor - LifeNews.com

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Will Gene Editing Allow Us to Rid the World of Diseases? – Healthline

By Sykes24Tracey

Scientists recently used a gene-editing tool to fix a mutation in a human embryo. Around the world, researchers are chasing cures for other genetic diseases.

Now that the gene-editing genie is out of the bottle, what would you wish for first?

Babies with perfect eyes, over-the-top intelligence, and a touch of movie star charisma?

Or a world free of disease not just for your family, but for every family in the world?

Based on recent events, many scientists are working toward the latter.

Earlier this month, scientists from the Oregon Health & Science University used a gene editing tool to correct a disease-causing mutation in an embryo.

The technique, known as CRISPR-Cas9, fixed the mutation in the embryos nuclear DNA that causes hypertrophic cardiomyopathy, a common heart condition that can lead to heart failure or cardiac death.

This is the first time that this gene-editing tool has been tested on clinical-quality human eggs.

Had one of these embryos been implanted into a womans uterus and allowed to fully develop, the baby would have been free of the disease-causing variation of the gene.

This type of beneficial change would also have been passed down to future generations.

None of the embryos in this study were implanted or allowed to develop. But the success of the experiment offers a glimpse at the potential of CRISPR-Cas9.

Still, will we ever be able to gene-edit our world free of disease?

According to the Genetic Disease Foundation, there are more than 6,000 human genetic disorders.

Scientists could theoretically use CRISPR-Cas9 to correct any of these diseases in an embryo.

To do this, they would need an appropriate piece of RNA to target corresponding stretches of genetic material.

The Cas9 enzyme cuts DNA at that spot, which allows scientists to delete, repair, or replace a specific gene.

Some genetic diseases, though, may be easier to treat with this method than others.

Most people are focusing, at least initially, on diseases where there really is only one gene involved or a limited number of genes and theyre really well understood, Megan Hochstrasser, PhD, science communications manager at the Innovative Genomics Institute in California, told Healthline.

Diseases caused by a mutation in a single gene include sickle cell disease, cystic fibrosis, and Tay-Sachs disease. These affect millions of people worldwide.

These types of diseases, though, are far outnumbered by diseases like cardiovascular disease, diabetes, and cancer, which kill millions of people across the globe each year.

Genetics along with environmental factors also contribute to obesity, mental illness, and Alzheimers disease, although scientists are still working on understanding exactly how.

Right now, most CRISPR-Cas9 research focuses on simpler diseases.

There are a lot of things that have to be worked out with the technology for it to get to the place where we could ever apply it to one of those polygenic diseases, where multiple genes contribute or one gene has multiple effects, said Hochstrasser.

Although designer babies gain a lot of media attention, much CRISPR-Cas9 research is focused elsewhere.

Most people who are working on this are not working in human embryos, said Hochstrasser. Theyre trying to figure out how we can develop treatments for people that already have diseases.

These types of treatments would benefit children and adults who are already living with a genetic disease, as well as people who develop cancer.

This approach may also help the 25 million to 30 million Americans who have one of the more than 6,800 rare diseases.

Gene editing is a really powerful option for people with rare disease, said Hochstrasser. You could theoretically do a phase I clinical trial with all the people in the world that have a certain [rare] condition and cure them all if it worked.

Rare diseases affect fewer than 200,000 people in the United States at any given time, which means there is less incentive for pharmaceutical companies to develop treatments.

These less-common diseases include cystic fibrosis, Huntingtons disease, muscular dystrophies, and certain types of cancer.

Last year researchers at the University of California Berkeley made progress in developing an ex vivo therapy where you take cells out of a person, modify them, and put them back into the body.

This treatment was for sickle cell disease. In this condition, a genetic mutation causes hemoglobin molecules to stick together, which deforms red blood cells. This can lead to blockages in the blood vessels, anemia, pain, and organ failure.

Researchers used CRISPR-Cas9 to genetically engineer stem cells to fix the sickle cell disease mutation. They then injected these cells into mice.

The stem cells migrated to the bone marrow and developed into healthy red blood cells. Four months later, these cells could still be found in the mices blood.

This is not a cure for the disease, because the body would continue to make red blood cells that have the sickle cell disease mutation.

But researchers think that if enough healthy stem cells take root in the bone marrow, it could reduce the severity of disease symptoms.

More work is needed before researchers can test this treatment in people.

A group of Chinese researchers used a similar technique last year to treat people with an aggressive form of lung cancer the first clinical trial of its kind.

In this trial, researchers modified patients immune cells to disable a gene that is involved in stopping the cells immune response.

Researchers hope that, once injected into the body, the genetically edited immune cells will mount a stronger attack against the cancer cells.

These types of therapies might also work for other blood diseases, cancers, or immune problems.

But certain diseases will be more challenging to treat this way.

If you have a disorder of the brain, for example, you cant remove someones brain, do gene editing and then put it back in, said Hochstrasser. So we have to figure out how to get these reagents to the places they need to be in the body.

Not every human disease is caused by mutations in our genome.

Vector-borne diseases like malaria, yellow fever, dengue fever, and sleeping sickness kill more than 1 million people worldwide each year.

Many of these diseases are transmitted by mosquitoes, but also by ticks, flies, fleas, and freshwater snails.

Scientists are working on ways to use gene editing to reduce the toll of these diseases on the health of people around the world.

We could potentially get rid of malaria by engineering mosquitoes that cant transmit the parasite that causes malaria, said Hochstrasser. We could do this using the CRISPR-Cas9 technique to push this trait through the entire mosquito population very quickly.

Researchers are also using CRISPR-Cas9 to create designer foods.

DuPont recently used gene editing to produce a new variety of waxy corn that contains higher amounts of starch, which has uses in food and industry.

Modified crops may also help reduce deaths due to malnutrition, which is responsible for nearly half of all deaths worldwide in children under 5.

Scientists could potentially use CRISPR-Cas9 to create new varieties of food that are pest-resistant, drought-resistant, or contain more micronutrients.

One benefit of CRISPR-Cas9, compared to traditional plant breeding methods, is that it allows scientists to insert a single gene from a related wild plant into a domesticated variety, without other unwanted traits.

Gene editing in agriculture may also move more quickly than research in people because there is no need for years of lab, animal, and human clinical trials.

Even though plants grow pretty slowly, said Hochstrasser, it really is quicker to get [genetically engineered plants] out into the world than doing a clinical trial in people.

Safety and ethical concerns

CRISPR-Cas9 is a powerful tool, but it also raises several concerns.

Theres a lot of discussion right now about how best to detect so-called off-target effects, said Hochstrasser. This is what happens when the [Cas9] protein cuts somewhere similar to where you want it to cut.

Off-target cuts could lead to unexpected genetic problems that cause an embryo to die. An edit in the wrong gene could also create an entirely new genetic disease that would be passed onto future generations.

Even using CRISPR-Cas9 to modify mosquitoes and other insects raises safety concerns like what happens when you make large-scale changes to an ecosystem or a trait in a population that gets out of control.

There are also many ethical issues that come with modifying human embryos.

So will CRISPR-Cas9 help rid the world of disease?

Theres no doubt that it will make a sizeable dent in many diseases, but its unlikely to cure all of them any time soon.

We already have tools for avoiding genetic diseases like early genetic screening of fetuses and embryos but these are not universally used.

We still dont avoid tons of genetic diseases, because a lot of people dont know that they harbor mutations that can be inherited, said Hochstrasser.

Some genetic mutations also happen spontaneously. This is the case with many cancers that result from environmental factors such as UV rays, tobacco smoke, and certain chemicals.

People also make choices that increase their risk of heart disease, stroke, obesity, and diabetes.

So unless scientists can use CRISPR-Cas9 to find treatments for these lifestyle diseases or genetically engineer people to stop smoking and start biking to work these diseases will linger in human society.

Things like that are always going to need to be treated, said Hochstrasser. I dont think its realistic to think we would ever prevent every disease from happening in a human.

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Will Gene Editing Allow Us to Rid the World of Diseases? - Healthline

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Chennai sprinter Blumen Rajan is in a race against time to beat cancer. Are you the stem cell donor who can help out … – EdexLive (press release)…

By Sykes24Tracey

Blumen has been diagnosed with Chronic Myeloid Leukemia and is awaiting a donor stem cell that matches his DNA

Running a difficult race isn't something that's new to Chennai-based BlumenRajan Sathya. An exceptionally gifted track athlete, a state record holder, a University gold medalist and a national level silver medalist in the 400m sprint, Blumenhad always been one to push his physical limits.

But this time, he's facing the most difficult track of his life. In December 2014, there was a sudden drop in his blood count. He was soon diagnosed with Chronic Myeloid Leukemia, a type of cancer which starts in certain blood-forming cells of the bone marrow.

CML is a treatable condition, where the first level of treatment is oral chemotherapy, followed by the usual induction chemo. However, the most-effective proven treatment is stem cell transplant, which is basically where you transplant a stem cell from a donor whose DNA matches with you."We've been hunting for donors. The only problem is that the probability of finding a match is one in a lakh. We're looking at international registries as well. I had contacted a registry in Germany while I did my homework online. But, they replied saying that the patient couldn't contact them directly," says the 27-year-old.

A graduate in Social Work from Madras Christian College and currently working with a local church, he adds, "In another three or four days, we will go ahead with the closest match available. We will wait for a hundred per cent match, but we can't wait too long."

When asked what kept him going strong throughout his whole battle, he says it was his faith in God and the support of his local church. Friends, family, colleagues and college mates have spread the word on social media, hoping for a miracle. Blumennow wants to ensure that there is awareness created about stem cell donation. "Most people have no clue about it. Most of us have never registered anywhere. There should be more awareness camps in colleges. If more people register, it would be much easier to find the right match. There won't be any trouble of finding volunteers," he says.

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Chennai sprinter Blumen Rajan is in a race against time to beat cancer. Are you the stem cell donor who can help out ... - EdexLive (press release)...

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‘Unexpected fountain of youth’ found in cardiac stem cells, says researcher – fox6now.com

By Sykes24Tracey

Cardiac stem cells derived from young hearts helped reverse the signs of aging when directly injected into the old hearts of elderly rats, astudypublished Monday in the European Heart Journal demonstrated.

The old rats appeared newly invigorated after receiving their injections. As hoped, the cardiac stem cells improved heart function yet also provided additional benefits. The rats fur, shaved for surgery, grew back more quickly than expected, and their chromosomal telomeres, which commonly shrink with age, lengthened.

The old rats receiving the cardiac stem cells also had increased stamina overall, exercising more than before the infusion.

Its extremely exciting, said Dr. Eduardo Marbn, primary investigator on the research and director of the Cedars-Sinai Heart Institute. Witnessing the systemic rejuvenating effects, he said, its kind of like an unexpected fountain of youth.

Weve been studying new forms of cell therapy for the heart for some 12 years now, Marbn said.

Some of this research has focused on cardiosphere-derived cells.

Theyre progenitor cells from the heart itself, Marbn said. Progenitor cells are generated from stem cells and share some, but not all, of the same properties. For instance, they can differentiate into more than one kind of cell like stem cells, but unlike stem cells, progenitor cells cannot divide and reproduce indefinitely.

From hisown previous research, Marbn discovered that cardiosphere-derived cells promote the healing of the heart after a condition known as heart failure with preserved ejection fraction, which affects more than 50% of all heart failure patients.

Since heart failure with preserved ejection fraction is similar to aging, Marbn decided to experiment on old rats, ones that suffered from a type of heart problem thats very typical of what we find in older human beings: The hearts stiff, and it doesnt relax right, and it causes fluid to back up some, Marbn explained.

He and his team injected cardiosphere-derived cells from newborn rats into the hearts of 22-month-old rats thats elderly for a rat. Similar old rats received a placebo injection of saline solution. Then, Marbn and his team compared both groups to young rats that were 4 months old. After a month, they compared the rats again.

Even though the cells were injected into the heart, their effects were noticeable throughout the body, Marbn said

The animals could exercise further than they could before by about 20%, and one of the most striking things, especially for me (because Im kind of losing my hair) the animals regrew their fur a lot better after theyd gotten cells compared with the placebo rats, Marbn said.

The rats that received cardiosphere-derived cells also experienced improved heart function and showed longer heart cell telomeres.

The working hypothesis is that the cells secrete exosomes, tiny vesicles that contain a lot of nucleic acids, things like RNA, that can change patterns of the way the tissue responds to injury and the way genes are expressed in the tissue, Marbn said.

It is the exosomes that act on the heart and make it better as well as mediating long-distance effects on exercise capacity and hair regrowth, he explained.

Looking to the future, Marbn said hes begun to explore delivering the cardiac stem cells intravenously in a simple infusion instead of injecting them directly into the heart, which would be a complex procedure for a human patient and seeing whether the same beneficial effects occur.

Dr. Gary Gerstenblith, a professor of medicine in the cardiology division of Johns Hopkins Medicine, said the new study is very comprehensive.

Striking benefits are demonstrated not only from a cardiac perspective but across multiple organ systems, said Gerstenblith, who did not contribute to the new research. The results suggest that stem cell therapies should be studied as an additional therapeutic option in the treatment of cardiac and other diseases common in the elderly.

Todd Herron, director of the University of Michigan Frankel Cardiovascular Centers Cardiovascular Regeneration Core Laboratory, said Marbn, with his previous work with cardiac stem cells, has led the field in this area.

The novelty of this bit of work is, they started to look at more precise molecular mechanisms to explain the phenomenon theyve seen in the past, said Herron, who played no role in the new research.

One strength of the approach here is that the researchers have taken cells from the organ that they want to rejuvenate, so that makes it likely that the cells stay there in that tissue, Herron said.

He believes that more extensive study, beginning with larger animals and including long-term followup, is needed before this technique could be used in humans.

We need to make sure theres no harm being done, Herron said, adding that extending the lifetime and improving quality of life amounts to a tradeoff between the potential risk and the potential good that can be done.

Capicor, the company that grows these special cells, is focused solely on therapies for muscular dystrophy and heart failure with ongoing clinical trials involving human patients, Marbn said.

Capicor hasnt announced any plans to do studies in aging, but the possibility exists.

After all, the cells have been proven completely safe in over 100 human patients, so it would be possible to fast-track them into the clinic, Marbn explained: I cant tell you that there are any plans to do that, but it could easily be done from a safety viewpoint.

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'Unexpected fountain of youth' found in cardiac stem cells, says researcher - fox6now.com

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