Stem Cell Clinic

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.

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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.

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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.

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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.

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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.

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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

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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.

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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.

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Induced stem cells - Wikipedia, the free encyclopedia

Pluripotency of Induced Pluripotent Stem Cells

By Induced Pluripotent Stem Cells

Volume 11, Issue 5, October 2013, Pages 299303

Special Issue: Induced Pluripotent Stem Cells

Edited By Qi Zhou

Induced pluripotent stem (iPS) cells can be generated by forced expression of four pluripotency factors in somatic cells. This has received much attention in recent years since it may offer us a promising donor cell source for cell transplantation therapy. There has been great progress in iPS cell research in the past few years. However, several issues need to be further addressed in the near future before the clinical application of iPS cells, like the immunogenicity of iPS cells, the variability of differentiation potential and most importantly tumor formation of the iPS derivative cells. Here, we review recent progress in research into the pluripotency of iPS cells.

Induced pluripotent stem (iPS) cells can be derived from mouse somatic cells via the ectopic expression of four defined factors, Oct4, Sox2, Klf4 and c-Myc (also known as Yamanaka factors) [1]. The mouse iPS cells express pluripotency markers and both X chromosomes are reactivated, allowing differentiation into various cell types of three germ layers when injected into a blastocyst. iPS technology makes reprogramming much easier [2]and[3] in comparison to early reprogramming methods such as somatic cell nuclear transfer (SCNT) [4]and[5], iPS technology also circumvents the ethical problems arising from the use of human oocytes. In addition, the generation of patient-specific iPS cells could be used to screen new drugs [6]and[7]. However, there are currently several limitations in applying iPS cells clinically. Efficiency of converting somatic cells to iPS cells is still very low. In particular, only approximately 0.1% to 1% of somatic cells experience changes at the transcriptional level and finally become pluripotent stem cells when non-integration approaches are used [8]. Moreover, compared to embryonic stem (ES) cells, the developmental potential and differentiation capacity of iPS cells is significantly reduced and there is increased variability among all iPS cell lines [9]. In mice, only small proportions of these cells are fully reprogrammed based on the most stringent tetraploid complementation assay for evaluating pluripotency [10], [11], [12]and[13]. Therefore, it is necessary to establish a strict molecular standard system to distinguish fully reprogrammed iPS cells from those partially reprogrammed, as we currently lack suitable in vivo pluripotency tests for human iPS cells.

In this review, we mainly focus on recent progress on rodent, non-human primate and human iPS cells, and point out some key questions which need to be addressed in the near future, such as the pluripotency level of human iPS cells and the establishment of a new standard to assess the pluripotency level of human iPS cells.

Takahashi and Yamanaka reprogrammed mouse embryonic fibroblasts by the ectopic expression of four reprogramming factors using retroviral vectors, and finally produced iPS cells which resemble ES cells [1]. This original iPS reprogramming approach used viral vectors, including retrovirus and lentivirus which possess high reprogramming efficiency [14]and[15]. The genome may be mutated by integrating other gene sequences, thus raising concerns on the safety issue. In addition, the insertion of oncogenes, like c-Myc, increases the risk of tumor formation [16]and[17]. Subsequently, several modified methods were used to obtain much safer iPS cells, for instance, piggyBac transposon [18], adenovirus [19], sendai virus [20], plasmid [21], episomal vectors [22] and minicircle vectors [23]. However, the reprogramming efficiency is significantly decreased and it takes longer to reactivate the key pluripotency markers to achieve full reprogramming. Therefore, efficient generation of non-integrated iPS cells by new approaches may promote their clinical application.

Recent studies have described several reprogramming methods using proteins, RNAs and small-molecule compounds to derive safe iPS cells [24], [25]and[26]. Zhou et al. obtained iPS cells induced by recombination of the proteins of the four Yamanaka factors obtained by fusing the C-terminus of the proteins with poly-arginine (11R) [24]. A recent study reported that mouse and human iPS cells can be efficiently generated by miRNA mediated reprogramming [25]. Miyoshi et al. [26] successfully generated iPS cells by direct transfection of human somatic cells using mature miRNA. iPS cells can also be generated by synthetic RNAs, which bypass the innate response to viruses [27]. Recently, Houet et al. [28] showed that pluripotent stem cells can be generated from mouse somatic cells at an efficiency of 0.2% by using a combination of seven small-molecule compounds. Compared to traditional viral methods, the aforementioned approaches can be used to generate qualified iPS cells (Table 1) without the risk of insertional mutagenesis. Nonetheless, some familiar drawbacks exist, such as a longer and less efficient reprogramming process. In other words, what we need to do next is to optimize non-integration induction systems in order to resolve these drawbacks.

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Pluripotency of Induced Pluripotent Stem Cells

Induced Pluripotent Stem Cells (IPSCs) – HowStuffWorks

By Induced Pluripotent Stem Cells

Save Those Teeth

Dentists usually discard wisdom teeth after they've been extracted -- but maybe they should start saving them; they just might be useful in make stem cells. Recently, a group of Japanese scientists made induced pluripotent stem cells (IPSCs) from the tooth pulp of extracted wisdom teeth. They used viruses to deliver stem cell factors to mesenchymal stromal cells isolated from the pulp of third molars. The resulting IPSCs were similar to embryonic stem cells.

In 2003, an NIH researcher, Sangtao Shi, extracted stem cells from his daughter's baby teeth. The stem cells grew in culture and could form bone when implanted into mice. Potentially, you could bank stem cells from your teeth for future use, but it would be an expensive process.

Maybe that's what the tooth fairy does with all those teeth?

Whether from embryos or adult tissues, stem cells are few. But many are needed for cell therapies. There have been ethical and political problems with using embryonic stem cells -- so if there were a way to get more stem cells from adults, it might be less controversial. Enter the IPSC.

Every cell in the body has the same genetic instructions. So what makes a heart cell different from a liver cell? The two cells express different sets of genes. Likewise, a stem cell turns on specific sets of genes to differentiate into another cell. So, is it possible to reprogram a differentiated cell so that it reverts back to a stem cell? In 2006, scientists did just that. They used a virus to deliver four stem cell factors into skin cells. The factors caused the differentiated stem cells to go into an embryonic-stem-cell-like state. The resulting cells, called induced pluripotent stem cells (IPSCs), shared many characteristics with human embryonic stem cells. The structures of IPSCs were similar, they expressed the same markers and genes, and they grew the same. And the researchers were able to grow the IPSCs into cell lines.

There are many more differentiated cells in the human body than stem cells, embryonic or adult. So, vast amounts of stem cells could be made from a patient's own differentiated cells, like skin cells. Making IPSCs does not involve embryos, so this would circumvent the ethical and political issues involved in stem cell research. However, making ISPSCs is a recent development, so scientists need to do more research before they can be used for therapies. First, we need to understand the "reprogramming" process better. And then we need to investigate whether IPSCs are just similar enough or are actually identical to embryonic stem cells. Current research is focused on these questions, but reprogramming cells to make IPSCs has great potential.

Now that you have a good idea of what stems cells are and how they work, let's see how they can be used to treat diseases.

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Induced Pluripotent Stem Cells (IPSCs) - HowStuffWorks

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