Stem Cell Clinic

Redox Signaling and Stem Cell Function – Dirk Bohmann

By Somatic Stem Cells

The activity of adult somatic stem cells has to be precisely controlled and adjusted to the organism's requirements. The underlying regulatory mechanisms are not well understood, but can be studied in the genetically tractable Drosophila intestinal stem cells (ISCs). Preliminary data generated in the laboratories of the two applicants have shown that cell stress and tissue damage can significantly increase the proliferative activity of ISCs. Strikingly, this activation of ISCs requires a concomitant decrease in cellular redox state. Redox based regulation of stem and progenitor cell function has been postulated before, but the genetic and mechanistic basis for this effect remains obscure. The preliminary data on which this proposal is based indicate a key role of the Nrf2 transcription factor, which has previously been mostly associated with antioxidant and detoxification programs. Upon stress exposure of ISCs, Nrf2 function is repressed, permitting the concentration of reactive oxygen species (ROS) to rise, and promoting proliferative competence of these cells. The down regulation of Nrf2 in response to stress and tissues injury is unique to stem cells and contrasts sharply with stress dependent activation of Nrf2 described in most other somatic cell types. The discovery of this unique Nrf2 signaling system that is restricted to stem cells raises interesting questions and offers opportunities for the targeted manipulation of stem cell function. This project will explore the distinctive regulation and the effects of Nrf2 in ISCs. Several lines of experimentation will explore how stress signaling affects Nrf2 to regulate ISC proliferation. Separate experiments will test the hypothesis that Nrf2 and redox control are universal mechanisms regulating stem cell activity, which are not only required to convey the response to direct cell damaging stress, but also to mediate the effects of endocrine differentiation signals. Finally, the mechanisms by which redox changes can alter stem cell function in such profound ways will be explored. For this latter aim experiments will be conducted to identify relevant redox sensing signaling molecules that control stem cell activity. The work described in this proposal will provide a mechanistic understanding of the redox-based mechanisms that control stem cell function and consequently tissue homeostasis. The goal is to test the model that Nrf2 activity determines a reduced, inactive state of ISCs, in which they are protected from oxidative stress, but cannot engage in regenerative processes. Down regulation of Nrf2 function by stress or mitogenic signaling then induces an oxidized state that allows regeneration to proceed. Validation of this model will confirm and mechanistically explain long standing theories on stem and progenitor cell regulation and may suggest strategies and targets for the manipulation of stem cell behavior, for example in cell transplantation paradigms or in the treatment of stem cell diseases.

Somatic stem cells are critical for tissue maintenance and regeneration. Controlling their regenerative capacity and proliferative activity is of fundamental importance for the maintenance of tissue homeostasis. This project investigates redox signaling as a central component of stem cell regulation.

See the original post here:
Redox Signaling and Stem Cell Function - Dirk Bohmann

Adult stem cell – Wikipedia, the free encyclopedia

By Somatic Stem Cells

Adult stem cells are undifferentiated cells, found throughout the body after development, that multiply by cell division to replenish dying cells and regenerate damaged tissues. Also known as somatic stem cells (from Greek , meaning of the body), they can be found in juvenile as well as adult animals and human bodies.

Scientific interest in adult stem cells is centered on their ability to divide or self-renew indefinitely, and generate all the cell types of the organ from which they originate, potentially regenerating the entire organ from a few cells. Unlike embryonic stem cells, the use of human adult stem cells in research and therapy is not considered to be controversial, as they are derived from adult tissue samples rather than human 5 day old embryos generated by IVF (in vitro fertility) clinics designated for scientific research. They have mainly been studied in humans and model organisms such as mice and rats.

A stem cell possesses two properties:

To ensure the safety of others, stem cells undergo two types of cell division (see Stem cell division and differentiation diagram). Symmetric division gives us a rise to two identical daughter cells, both endowed with stem cell properties, whereas asymmetric such division produces only one of those stem cells and a progenitor cell with limited self-renewal potential. Progenitors can go through several rounds of cell division before finally differentiating into a mature cell. It is believed that the molecular distinction between symmetric and asymmetric divisions lies in differential segregation of cell membrane proteins (such as receptors) between the daughter cells.

Adult stem cells express transporters of the ATP-binding cassette family that actively pump a diversity of organic molecules out of the cell.[2] Many pharmaceuticals are exported by these transporters conferring multidrug resistance onto the cell. This complicates the design of drugs, for instance neural stem cell targeted therapies for the treatment of clinical depression.

Adult stem cell research has been focused on uncovering the general molecular mechanisms that control their self-renewal and differentiation.

Discoveries in recent years have suggested that adult stem cells might have the ability to differentiate into cell types from different germ layers. For instance, neural stem cells from the brain, which are derived from ectoderm, can differentiate into ectoderm, mesoderm, and endoderm.[5] Stem cells from the bone marrow, which is derived from mesoderm, can differentiate into liver, lung, GI tract and skin, which are derived from endoderm and mesoderm.[6] This phenomenon is referred to as stem cell transdifferentiation or plasticity. It can be induced by modifying the growth medium when stem cells are cultured in vitro or transplanting them to an organ of the body different from the one they were originally isolated from. There is yet no consensus among biologists on the prevalence and physiological and therapeutic relevance of stem cell plasticity. More recent findings suggest that pluripotent stem cells may reside in blood and adult tissues in a dormant state.[7] These cells are referred to as "Blastomere Like Stem Cells" (Am Surg. 2007 Nov;73:1106-10) and "very small embryonic like" - "VSEL" stem cells, and display pluripotency in vitro.[7] As BLSC's and VSEL cells are present in virtually all adult tissues, including lung, brain, kidneys, muscles, and pancreas[8] Co-purification of BLSC's and VSEL cells with other populations of adult stem cells may explain the apparent pluripotency of adult stem cell populations. However, recent studies have shown that both human and murine VSEL cells lack stem cell characteristics and are not pluripotent.[9][10][11][12]

Stem cell function becomes impaired with age, and this contributes to progressive deterioration of tissue maintenance and repair.[13] A likely important cause of increasing stem cell dysfunction is age-dependent accumulation of DNA damage in both stem cells and the cells that comprise the stem cell environment.[13] (See also DNA damage theory of aging.)

Hematopoietic stem cells are found in the bone marrow and give rise to all the blood cell types.

Mammary stem cells provide the source of cells for growth of the mammary gland during puberty and gestation and play an important role in carcinogenesis of the breast.[14] Mammary stem cells have been isolated from human and mouse tissue as well as from cell lines derived from the mammary gland. Single such cells can give rise to both the luminal and myoepithelial cell types of the gland, and have been shown to have the ability to regenerate the entire organ in mice.[14]

Read this article:
Adult stem cell - Wikipedia, the free encyclopedia

PRP Therapy | PRP Injections for Knee

By Platelet Rich Plasma Injections

Platelets and accompanying stem cells are responsible for repair, whether in healing an injury or recovering from surgery. Platelets are found circulating in the blood in relatively small numbers. By concentrating the platelets drawn from your own blood supply, we are able to harness the power of platelets to relieve pain and stop inflammation for orthopedic disorders and injuries.

Platelet rich plasma injections are replacing traditional orthopedic surgery in many instances for conditions ranging from soft tissue injuries (tendonitis, muscle tears, ligamentous injuries) to various joint afflictions, such as a torn meniscus or mild to moderate arthritis of the joint.

PRP therapeutic treatment at the Institute of Regenerative & Molecular Orthopaedics typically requires two PRP injections into the injured tissue. Each procedure takes approximately 35 minutes to complete. The injections will likely be four to six weeks apart. Occasionally, a third PRP injection is needed.

There are some unique aspects of a PRP treatment performed by the Institute of Regenerative and Molecular Orthopedics. We are one of the few facilities in the world that uses an enhanced PRP with growth factors that are injected along with the PRP. We call this a Rx PRP. These additional growth factors dramatically increase the chances of success. Furthermore we will enhance the PRP by the process of photo-modulation.

The methods used to inject the PRP depend on the area being treated. For certain joints, such as the hip, we utilize fluoroscopy, which is a living x-ray. In other instances, we utilize ultrasound guidance or simply give the injection into a joint.

The aftercare for most PRP injections is relatively simple. Patients will resume activity at their own pace. The pain from the process typically will last a few days, occasionally longer, and some patients have more severe or sporadic pain than others. Because your own blood is used, there is no risk of a transmittable infection and a very low risk of allergic reaction to the treatment.

After the PRP injections a variety of techniques to help maximize stem cell output from the bone marrow are utilized including the use of supplements, as well as the avoidance of smoking and alcohol intake, which diminish stem cell output. Additionally, non-steroidal anti-inflammatory drugs (NSAID) will be restricted for just a couple of days.

We do not employ any clotting agents, such as thrombin, with our PRP. It is not necessary and could actually be detrimental since using a clotting agent releases the growth factors all at once rather than through a prolonged release.

We strongly encourage you learn more about the science of PRP therapy. If you are considering having a PRP procedure done, you owe it to yourself to have a better understanding of the methods being used and the questions you should be asking.

Link:
PRP Therapy | PRP Injections for Knee

Platelet-rich plasma therapy PRP Injections

By Platelet Rich Plasma Injections

Harnessing the innate power of the body to heal is one of the keys to optimal repair and regeneration. Natural substances found in the plasma are necessary to healing damaged cells and tissues. Platelet-rich plasma therapy utilizes these substances, providing areas of injury or disease with a concentrated dose of the bodys own specific platelets, proteins and growth factors.

Platelets and PRP Injections

Platelets are best known for their ability to coagulate to stop bleeding; however, new evidence indicates that platelets also produce growth factors needed to mend and strengthen damaged tissues. By extracting a patients plasma and centrifuging it, these important substances can be isolated. After separation, they are placed in a syringe and injected into a specific area or joint, such as the knee or hip, giving the damaged tissues more than enough healing factors to begin the process of repair.

Uses of PRP

Conditions Commonly Treated with PRP Shoulder: Rotator Cuff Tendinitis or Tear, Rotator Cuff Impingement Syndrome or Bursitis, Bicipital Tendinitis, labrum tears, arthritis, instability Wrist/Hand: DeQuervaines Tenosynovitis, arthritis, other wrist or finger tendinitis, ligament tears or dysfunction of the fingers Elbow: Medial and lateral epicondylitis (tennis & golfers elbow) Hip: IIliotibial Band Tendinitis (ITB Syndrome), Psoas Tendinitis and bursitis, Greater Trochanteric Bursitis, Hip labrum tears, Piriformis Syndrome, Sacroiliac Joint Dysfunction, arthritis Knee: Patellar Tendinitis, Patellar Femoral Syndrome, chondromalacia patella, partially torn or strained major ligaments of knee (ACL/LCL/MCL), meniscus tears, arthritis, patellar instability Ankle/Foot: Achilles Tendinitis, Peroneal Tendinitis, arthritis, recurrent ankle sprains, other foot or ankle tendinitis

Conditions Considered for Treatment with PRP or Prolotherapy Neck: Whiplash injuries, headaches related to the neck, arthritis Back: Facet joint arthritis, rib problems, pain associated with scoliosis

Results and Side Effects

You may experience initial pain at the injection site, though Orthohealing Centers physicians can use specific substances to help numb the area. Typically, however, the pain is short-lived, and you may begin to feel relief from chronic pain soon after the injection is administered. Results can last a year or more, as the body is using a concentrated dose of its own building blocks. To read some of Orthohealing Centers platelet-rich plasma therapy success stories and patient testimonials, click here.

What to Expect at Orthohealing Center

The physicians at Orthohealing Center are considered leaders in the world of ultrasound guided PRP therapy, giving lectures and hosting seminars dedicated to training doctors around the world in this new technique. As experts in orthopedic medicine and Orthobiologics, they provide individualized care, rather than a cookie cutter approach to healing. Each patient case is unique, and each physician incorporates adjunct therapies to enhance your platelet-rich plasma injections.

View post:
Platelet-rich plasma therapy PRP Injections

Sickle-cell disease – Wikipedia, the free encyclopedia

By Uncategorized

Sickle-cell disease (SCD), also known as sickle-cell anaemia (SCA) and drepanocytosis, is a hereditary blood disorder, characterized by an abnormality in the oxygen-carrying haemoglobin molecule in red blood cells. This leads to a propensity for the cells to assume an abnormal, rigid, sickle-like shape under certain circumstances. Sickle-cell disease is associated with a number of acute and chronic health problems, such as severe infections, attacks of severe pain ("sickle-cell crisis"), and stroke, and there is an increased risk of death.

Sickle-cell disease occurs when a person inherits two abnormal copies of the haemoglobin gene, one from each parent. Several subtypes exist, depending on the exact mutation in each haemoglobin gene. A person with a single abnormal copy does not experience symptoms and is said to have sickle-cell trait. Such people are also referred to as carriers.

The complications of sickle-cell disease can be prevented to a large extent with vaccination, preventive antibiotics, blood transfusion, and the drug hydroxyurea/hydroxycarbamide. A small proportion requires a transplant of bone marrow cells.

Almost 300,000 children are born with a form of sickle-cell disease every year, mostly in sub-Saharan Africa, but also in other parts of the world such as the West Indies and in people of African origin elsewhere in the world. In 2013 it resulted in 176,000 deaths up from 113,000 deaths in 1990.[1] The condition was first described in the medical literature by the American physician James B. Herrick in 1910, and in the 1940s and 1950s contributions by Nobel prize-winner Linus Pauling made it the first disease where the exact genetic and molecular defect was elucidated.

Sickle-cell disease may lead to various acute and chronic complications, several of which have a high mortality rate.[2]

The terms "sickle-cell crisis" or "sickling crisis" may be used to describe several independent acute conditions occurring in patients with SCD. SCD results in anemia and crises that could be of many types including the vaso-occlusive crisis, aplastic crisis, sequestration crisis, haemolytic crisis, and others. Most episodes of sickle-cell crises last between five and seven days.[3] "Although infection, dehydration, and acidosis (all of which favor sickling) can act as triggers, in most instances, no predisposing cause is identified."[4]

The vaso-occlusive crisis is caused by sickle-shaped red blood cells that obstruct capillaries and restrict blood flow to an organ resulting in ischaemia, pain, necrosis, and often organ damage. The frequency, severity, and duration of these crises vary considerably. Painful crises are treated with hydration, analgesics, and blood transfusion; pain management requires opioid administration at regular intervals until the crisis has settled. For milder crises, a subgroup of patients manage on NSAIDs (such as diclofenac or naproxen). For more severe crises, most patients require inpatient management for intravenous opioids; patient-controlled analgesia devices are commonly used in this setting. Vaso-occlusive crisis involving organs such as the penis[5] or lungs are considered an emergency and treated with red-blood cell transfusions. Incentive spirometry, a technique to encourage deep breathing to minimise the development of atelectasis, is recommended.[6]

Because of its narrow vessels and function in clearing defective red blood cells, the spleen is frequently affected.[7] It is usually infarcted before the end of childhood in individuals suffering from sickle-cell anemia. This spleen damage increases the risk of infection from encapsulated organisms;[8][9] preventive antibiotics and vaccinations are recommended for those lacking proper spleen function.

Splenic sequestration crises are acute, painful enlargements of the spleen, caused by intrasplenic trapping of red cells and resulting in a precipitous fall in hemoglobin levels with the potential for hypovolemic shock. Sequestration crises are considered an emergency. If not treated, patients may die within 12 hours due to circulatory failure. Management is supportive, sometimes with blood transfusion. These crises are transient, they continue for 34 hours and may last for one day.[10]

Acute chest syndrome (ACS) is defined by at least two of the following signs or symptoms: chest pain, fever, pulmonary infiltrate or focal abnormality, respiratory symptoms, or hypoxemia.[11] It is the second-most common complication and it accounts for about 25% of deaths in patients with SCD, majority of cases present with vaso-occlusive crises then they develop ACS.[12][13] Nevertheless, about 80% of patients have vaso-occlusive crises during ACS.

Read the original here:
Sickle-cell disease - Wikipedia, the free encyclopedia

T Cell Therapy (CTL019) | The Children’s Hospital of …

By Uncategorized

CTL019 is a clinical trial of T cell therapyfor patients with B cell cancers such as acute lymphoblastic leukemia (ALL), B cell non-Hodgkin lymphoma (NHL), and the adult disease chronic lymphocytic leukemia (CLL). At this time, The Children's Hospital of Philadelphia is the only hospital enrolling pediatric patientson this trial.

In July 2014, CTL019 was awarded Breakthrough Therapy designation by the U.S. Food and Drug Administration for the treatment of relapsed and refractory adult and pediatric acute lymphoblastic leukemia (ALL). The investigational therapy is the first personalized cellular therapy for the treatment of cancer to receive this important classification.

In this clinical trial, immune cells called T cells are taken from a patient's own blood. These cells are genetically modified to express a protein which will recognize and bind to a target called CD19, which is found on cancerous B cells. This is how T cell therapy works:

30 patients with acute lymphoblastic leukemia (25 children and 5 adults) have been treatedusing T cell therapy.Of those patients:

The most recent results were published in The New England Journal of Medicine in October 2014. Scientists at The Childrens Hospital of Philadelphia and the University of Pennsylvania are very hopeful that CTL019 could in the future be an effective therapy for patients with B cell cancers. However, because so few patients have been treated, and because those patients have been followed for a relatively shorttime,it is critical that more adult and pediatric patients are enrolled in the study to determine whether a larger group of patients with B cell cancers will have the same response, and maintain that response.

At this point CHOP's capability to enroll patients is limited because of the need to manufacture the T cell product used in this therapy. Our goal is to boost enrollment soon, by increasing our manufacturing capabilities and by broadening this study to other pediatric hospitals.

T cell therapy is a treatment for children and adolescents with fairly advanced B cell acute lymphoblastic leukemia (ALL) and B cell lymphomas, but not other leukemias or pediatric cancers. It is an option for those patients who have very resistant ALL.

Roughly 85 percent of ALL cases are treated very successfully with standard chemotherapy. For the remaining 15 percent of cases, representing a substantial number of children in the United States, chemotherapy only works temporarily or not at all. This is not a treatment for newly diagnosed leukemia, only for patients whose leukemia is not responding to chemotherapy,and whose disease has come back after a bone marrow transplant.

It is important to note that while results of this study are encouraging, it is still very early in testing and that not all children who qualify for the trial will have the same result.

Read this article:
T Cell Therapy (CTL019) | The Children's Hospital of ...

Induced pluripotent stem cell – Wikipedia, the free …

By Adult Stem Cells

Induced pluripotent stem cells (also known as iPS cells or iPSCs) are a type of pluripotent stem cell that can be generated directly from adult cells. The iPSC technology was pioneered by Shinya Yamanakas lab in Kyoto, Japan, who showed in 2006 that the introduction of four specific genes encoding transcription factors could convert adult cells into pluripotent stem cells.[1] He was awarded the 2012 Nobel Prize along with Sir John Gurdon "for the discovery that mature cells can be reprogrammed to become pluripotent." [2]

Pluripotent stem cells hold great promise in the field of regenerative medicine. Because they can propagate indefinitely, as well as give rise to every other cell type in the body (such as neurons, heart, pancreatic, and liver cells), they represent a single source of cells that could be used to replace those lost to damage or disease.

The most well-known type of pluripotent stem cell is the embryonic stem cell. However, since the generation of embryonic stem cells involves destruction (or at least manipulation) [3] of the pre-implantation stage embryo, there has been much controversy surrounding their use. Further, because embryonic stem cells can only be derived from embryos, it has so far not been feasible to create patient-matched embryonic stem cell lines.

Since iPSCs can be derived directly from adult tissues, they not only bypass the need for embryos, but can be made in a patient-matched manner, which means that each individual could have their own pluripotent stem cell line. These unlimited supplies of autologous cells could be used to generate transplants without the risk of immune rejection. While the iPSC technology has not yet advanced to a stage where therapeutic transplants have been deemed safe, iPSCs are readily being used in personalized drug discovery efforts and understanding the patient-specific basis of disease.[citation needed]

Depending on the methods used, reprogramming of adult cells to obtain iPSCs may pose significant risks that could limit their use in humans. For example, if viruses are used to genomically alter the cells, the expression of cancer-causing genes "oncogenes" may potentially be triggered. In February 2008, scientists announced the discovery of a technique that could remove oncogenes after the induction of pluripotency, thereby increasing the potential use of iPS cells in human diseases.[4] In April 2009, it was demonstrated that generation of iPS cells is possible without any genetic alteration of the adult cell: a repeated treatment of the cells with certain proteins channeled into the cells via poly-arginine anchors was sufficient to induce pluripotency.[5] The acronym given for those iPSCs is piPSCs (protein-induced pluripotent stem cells).

iPSCs are typically derived by introducing a specific set of pluripotency-associated genes, or reprogramming factors, into a given cell type. The original set of reprogramming factors (also dubbed Yamanaka factors) are the genes Oct4 (Pou5f1), Sox2, cMyc, and Klf4. While this combination is most conventional in producing iPSCs, each of the factors can be functionally replaced by related transcription factors, miRNAs, small molecules, or even non-related genes such as lineage specifiers.

iPSC derivation is typically a slow and inefficient process, taking 12 weeks for mouse cells and 34 weeks for human cells, with efficiencies around 0.01%0.1%. However, considerable advances have been made in improving the efficiency and the time it takes to obtain iPSCs. Upon introduction of reprogramming factors, cells begin to form colonies that resemble pluripotent stem cells, which can be isolated based on their morphology, conditions that select for their growth, or through expression of surface markers or reporter genes.

Induced pluripotent stem cells were first generated by Shinya Yamanaka's team at Kyoto University, Japan, in 2006.[1] Their hypothesis was that genes important to embryonic stem cell function might be able to induce an embryonic state in adult cells. They began by choosing twenty-four genes that were previously identified as important in embryonic stem cells, and used retroviruses to deliver these genes to fibroblasts from mice. The mouse fibroblasts were engineered so that any cells that reactivated the ESC-specific gene, Fbx15, could be isolated using antibiotic selection.

Upon delivery of all twenty-four factors, colonies emerged that had reactivated the Fbx15 reporter, resembled ESCs, and could propagate indefinitely. They then narrowed their candidates by removing one factor at a time from the pool of twenty-four. By this process, they identified four factors, Oct4, Sox2, cMyc, and Klf4, which as a group were both necessary and sufficient to obtain ESC-like colonies under selection for reactivation of Fbx15.

Similar to ESCs, these first-generation iPSCs showed unlimited self-renewal and demonstrated pluripotency by contributing to lineages from all three germ layers in the context of embryoid bodies, teratomas, fetal chimeras. However, the molecular makeup of these cells, including gene expression and epigenetic marks, was somewhere between that of a fibroblast and an ESC, and the cells also failed to produce viable chimeras when injected into developing embryos.

Read more from the original source:
Induced pluripotent stem cell - Wikipedia, the free ...

Stem Cell Clinics List | Stem Cells Freak

By Stem Cell Clinics

Here we have compiled a list of several clinics offering stem cell treatments. Please note that the "conditions treated" refers to the conditions that THEY claim to treat. Most, if not all, stem cell treatments (except hematopoietic stem cell transplantation) aren't FDA approved, meaning that they haven't been clincally tested for safety or efficacy. Please be aware that receiving an unapproved medical treatment isrisky and may cause serious complications and possibly death.

It was only a few years ago when Europe's most popular stem cell clinic (XCell-center) was forced to close after one of the treatments caused the death of a boy. In the past, we have also covered the case of a woman that had serious adverse effects following an unapproved cosmetic stem cell treatment(facelift).

We have not included clinics offering hematopoietic stem cell transplantation, as this treatment is medically approved and offered virtually in any country that has an above the average hospital.

The stem cell clinics are categorised by alphabetical order. We are not paid by any of them and we have listed them for your ease. We have probably missed a few ones, feel free to leave a comment and we will add them asap.

Stem cell clinics list

Beijing Puhua International Hospital

Conditions Treated:Diabetes, Epilepsy, Stroke, Ataxia, Spinal Cord Injuries, Parkinson's Disease, Brain Injury, Multiple Sclerosis, Batten's Disease

Interview of a patient treated in Beijing Puhua International Hospital. The video is from the hospital's official youtube channel, so it may be biased

Elises International

Conditions Treated: No info available at their website

More:
Stem Cell Clinics List | Stem Cells Freak

Induced Pluripotent Stem Cells (iPS) | UCLA Broad Stem …

By Induced Pluripotent Stem Cells

iPSC are derived from skin or blood cells that have been reprogrammed back into an embryonic-like pluripotent state that enables the development of an unlimited source of any type of human cell needed for therapeutic purposes. For example, iPSC can be prodded into becoming beta islet cells to treat diabetes, blood cells to create new blood free of cancer cells for a leukemia patient, or neurons to treat neurological disorders.

In late 2007, a BSCRC team of faculty, Drs. Kathrin Plath, William Lowry, Amander Clark, and April Pyle were among the first in the world to create human iPSC. At that time, science had long understood that tissue specific cells, such as skin cells or blood cells, could only create other like cells. With this groundbreaking discovery, iPSC research has quickly become the foundation for a new regenerative medicine.

Using iPSC technology our faculty have reprogrammed skin cells into active motor neurons, egg and sperm precursors, liver cells, bone precursors, and blood cells. In addition, patients with untreatable diseases such as, ALS, Rett Syndrome, Lesch-Nyhan Disease, and Duchenne's Muscular Dystrophy donate skin cells to BSCRC scientists for iPSC reprogramming research. The generous participation of patients and their families in this research enables BSCRC scientists to study these diseases in the laboratory in the hope of developing new treatment technologies.

See the article here:
Induced Pluripotent Stem Cells (iPS) | UCLA Broad Stem ...

Induced stem cells – Wikipedia, the free encyclopedia

By Induced Pluripotent Stem Cells

Induced stem cells (iSC) are stem cells artificially derived from somatic, reproductive, pluripotent or other cell types by deliberate epigenetic reprogramming. They are classified as either totipotent (iTC), pluripotent (iPSC) or progenitor (multipotentiMSC, also called an induced multipotent progenitor celliMPC) or unipotent -- (iUSC) according to their developmental potential and degree of dedifferentiation. Progenitors are obtained by so-called direct reprogramming or directed differentiation and are also called induced somatic stem cells.

Three techniques are widely recognized:[1]

Back in 1895, Thomas Morgan remove one of the two frog blastomeres and found that amphibians are able to form whole embryo from the remaining part. This meant that the cells can change their differentiation pathway. Later, in 1924, Spemann and Mangold demonstrated the key importance of cellcell inductions during animal development.[20] The reversible transformation of cells of one differentiated cell type to another is called metaplasia.[21] This transition can be a part of the normal maturation process, or caused by an inducing stimulus. For example: transformation of iris cells to lens cells in the process of maturation and transformation of retinal pigment epithelium cells into the neural retina during regeneration in adult newt eyes. This process allows the body to replace cells not suitable to new conditions with more suitable new cells. In Drosophila imaginal discs, cells have to choose from a limited number of standard discrete differentiation states. The fact that transdetermination (change of the path of differentiation) often occurs for a group of cells rather than single cells shows that it is induced rather than part of maturation.[22]

The researchers were able to identify the minimal conditions and factors that would be sufficient for starting the cascade of molecular and cellular processes to instruct pluripotent cells to organize the embryo. They show that opposing gradients of bone morphogenetic protein (BMP) and Nodal, two transforming growth factor family members that act as morphogens, are sufficient to induce molecular and cellular mechanisms required to organize, in vivo or in vitro, uncommitted cells of the zebrafish blastula animal pole into a well-developed embryo.[23]

Some types of mature, specialized adult cells can naturally revert to stem cells. For example, "chief" cells express the stem cell marker Troy. While they normally produce digestive fluids for the stomach, they can revert into stem cells to make temporary repairs to stomach injuries, such as a cut or damage from infection. Moreover, they can make this transition even in the absence of noticeable injuries and are capable of replenishing entire gastric units, in essence serving as quiescent reserve stem cells.[24] Differentiated airway epithelial cells can revert into stable and functional stem cells in vivo.[25]

After injury, mature terminally differentiated kidney cells dedifferentiate into more primordial versions of themselves, and then differentiate into the cell types needing replacement in the damaged tissue[26] Macrophages can self-renew by local proliferation of mature differentiated cells.[27] In newts, muscle tissue is regenerated from specialized muscle cells that dedifferentiate and forget the type of cell they had been. This capacity to regenerate does not decline with age and may be linked to their ability to make new stem cells from muscle cells on demand.[28]

A variety of nontumorigenic stem cells display the ability to generate multiple cell types. For instance, multilineage-differentiating stress-enduring (Muse) cells are stress-tolerant adult human stem cells that can self-renew. They form characteristic cell clusters in suspension culture that express a set of genes associated with pluripotency and can differentiate into endodermal, ectodermal and mesodermal cells both in vitro and in vivo.[29][30][31][32][33]

Other well-documented examples of transdifferentiation and their significance in development and regeneration were described in detail.[34]

Induced totipotent cells can be obtained by reprogramming somatic cells with somatic-cell nuclear transfer (SCNT). The process involves sucking out the nucleus of a somatic (body) cell and injecting it into an oocyte that has had its nucleus removed[3][5][35][36]

Using an approach based on the protocol outlined by Tachibana et al.,[3] hESCs can be generated by SCNT using dermal fibroblasts nuclei from both a middle-aged 35-year-old male and an elderly, 75-year-old male, suggesting that age-associated changes are not necessarily an impediment to SCNT-based nuclear reprogramming of human cells.[37] Such reprogramming of somatic cells to a pluripotent state holds huge potentials for regenerative medicine. Unfortunately, the cells generated by this technology, potentially are not completely protected from the immune system of the patient (donor of nuclei), because they have the same mitochondrial DNA, as a donor of oocytes, instead of the patients mitochondrial DNA. This reduces their value as a source for autologous stem cell transplantation therapy, as for the present, it is not clear whether it can induce an immune response of the patient upon treatment.

Visit link:
Induced stem cells - Wikipedia, the free encyclopedia

→←