Cancer stem cell – Wikipedia

Cancer stem cells (CSCs) are cancer cells (found within tumors or hematological cancers) that possess characteristics associated with normal stem cells, specifically the ability to give rise to all cell types found in a particular cancer sample. CSCs are therefore tumorigenic (tumor-forming), perhaps in contrast to other non-tumorigenic cancer cells. CSCs may generate tumors through the stem cell processes of self-renewal and differentiation into multiple cell types. Such cells are hypothesized to persist in tumors as a distinct population and cause relapse and metastasis by giving rise to new tumors. Therefore, development of specific therapies targeted at CSCs holds hope for improvement of survival and quality of life of cancer patients, especially for patients with metastatic disease.

Existing cancer treatments have mostly been developed based on animal models, where therapies able to promote tumor shrinkage were deemed effective. However, animals do not provide a complete model of human disease. In particular, in mice, whose life spans do not exceed two years, tumor relapse is difficult to study.

The efficacy of cancer treatments is, in the initial stages of testing, often measured by the ablation fraction of tumor mass (fractional kill). As CSCs form a small proportion of the tumor, this may not necessarily select for drugs that act specifically on the stem cells. The theory suggests that conventional chemotherapies kill differentiated or differentiating cells, which form the bulk of the tumor but do not generate new cells. A population of CSCs, which gave rise to it, could remain untouched and cause relapse.

Cancer stem cells were first identified by John Dick in acute myeloid leukemia in the late 1990s. Since the early 2000s they have been an intense cancer research focus.[1]

In different tumor subtypes, cells within the tumor population exhibit functional heterogeneity and tumors are formed from cells with various proliferative and differentiation capacities.[2] This functional heterogeneity among cancer cells has led to the creation of multiple propagation models to account for heterogeneity and differences in tumor-regenerative capacity: the cancer stem cell (CSC) and stochastic model.

The Cancer Stem Cell Model, also known as the Hierarchical Model proposes that tumors are hierarchically organized (CSCs lying at the apex[3] (Fig. 3).) Within the cancer population of the tumors there are cancer stem cells (CSC) that are tumorigenic cells and are biologically distinct from other subpopulations[4] They have two defining features: their long-term ability to self-renew and their capacity to differentiate into progeny that is non-tumorigenic but still contributes to the growth of the tumor. This model suggests that only certain subpopulations of cancer stem cells have the ability to drive the progression of cancer, meaning that there are specific (intrinsic) characteristics that can be identified and then targeted to destroy a tumor long-term without the need to battle the whole tumor [5]

In order for a cell to become cancerous it must undergo a significant number of alterations to its DNA sequence. This cell model suggests these mutations could occur to any cell in the body resulting in a cancer. Essentially this theory proposes that all cells have the ability to be tumorigenic making all tumor cells equipotent with the ability to self-renew or differentiate, leading to tumor heterogeneity while others can differentiate into non-CSCs [4][6] The cell's potential can be influenced by unpredicted genetic or epigenetic factors, resulting in phenotypically diverse cells in both the tumorigenic and non-tumorigenic cells that compose the tumor.[7]

These mutations could progressively accumulate and enhance the resistance and fitness of cells that allow them to outcompete other tumor cells, better known as the somatic evolution model.[4] The clonal evolution model, which occurs in both the CSC model and stochastic model, postulates that mutant tumor cells with a growth advantage outproliferate others. Cells in the dominant population have a similar potential for initiating tumor growth[8] (Fig. 4).

[9] These two models are not mutually exclusive, as CSCs themselves undergo clonal evolution. Thus, the secondary more dominant CSCs may emerge, if a mutation confers more aggressive properties[10] (Fig. 5).

A study in 2014 argues the gap between these two controversial models can be bridged by providing an alternative explanation of tumor heterogeneity. They demonstrate a model that includes aspects of both the Stochastic and CSC models.[6] They examined cancer stem cell plasticity in which cancer stem cells can transition between non-cancer stem cells (Non-CSC) and CSC via in situ supporting a more Stochastic model.[6][11] But the existence of both biologically distinct non-CSC and CSC populations supports a more CSC model, proposing that both models may play a vital role in tumor heterogeneity.[6]

The existence of CSCs is under debate, because many studies found no cells with their specific characteristics.[12] Cancer cells must be capable of continuous proliferation and self-renewal to retain the many mutations required for carcinogenesis and to sustain the growth of a tumor, since differentiated cells (constrained by the Hayflick Limit[13]) cannot divide indefinitely. If most tumor cells are endowed with stem cell properties, targeting tumor size directly is a valid strategy. If they are a small minority, targeting them may be more effective. Another debate is over the origin of CSCs - whether from disregulation of normal stem cells or from a more specialized population that acquired the ability to self-renew (which is related to the issue of stem cell plasticity).

The first conclusive evidence for CSCs came in 1997. Bonnet and Dick isolated a subpopulation of leukemia cells that expressed surface marker CD34, but not CD38.[14] The authors established that the CD34+/CD38 subpopulation is capable of initiating tumors in NOD/SCID mice that were histologically similar to the donor. The first evidence of a solid tumor cancer stem-like cell followed in 2002 with the discovery of a clonogenic, sphere-forming cell isolated and characterized from human brain gliomas. Human cortical glial tumors contain neural stem-like cells expressing astroglial and neuronal markers in vitro.[15]

In cancer research experiments, tumor cells are sometimes injected into an experimental animal to establish a tumor. Disease progression is then followed in time and novel drugs can be tested for their efficacy. Tumor formation requires thousands or tens of thousands of cells to be introduced. Classically, this was explained by poor methodology (i.e., the tumor cells lose their viability during transfer) or the critical importance of the microenvironment, the particular biochemical surroundings of the injected cells. Supporters of the CSC paradigm argue that only a small fraction of the injected cells, the CSCs, have the potential to generate a tumor. In human acute myeloid leukemia the frequency of these cells is less than 1 in 10,000.[14]

Further evidence comes from histology. Many tumors are heterogeneous and contain multiple cell types native to the host organ. Heterogeneity is commonly retained by tumor metastases. This suggests that the cell that produced them had the capacity to generate multiple cell types, a classical hallmark of stem cells.[14]

The existence of leukemia stem cells prompted research into other cancers. CSCs have recently been identified in several solid tumors, including:

Once the pathways to cancer are hypothesized, it is possible to develop predictive mathematical models,[33] e.g., based on the cell compartment method. For instance, the growths of abnormal cells can be denoted with specific mutation probabilities. Such a model predicted that repeated insult to mature cells increases the formation of abnormal progeny and the risk of cancer.[34] The clinical efficacy of such models[35] remains unestablished.

The origin of CSCs is an active research area. The answer may depend on the tumor type and phenotype. So far the hypothesis that tumors originate from a single "cell of origin" has not been demonstrated using the cancer stem cell model. This is because cancer stem cells are not present in end-stage tumors.

Origin hypotheses include mutants in developing stem or progenitor cells, mutants in adult stem cells or adult progenitor cells and mutant, differentiated cells that acquire stem-like attributes. These theories often focus on a tumor's "cell of origin".

The "mutation in stem cell niche populations during development" hypothesis claims that these developing stem populations are mutated and then reproduce so that the mutation is shared by many descendants. These daughter cells are much closer to becoming tumors and their numbers increase the chance of a cancerous mutation.[36]

Another theory associates adult stem cells (ASC) with tumor formation. This is most often associated with tissues with a high rate of cell turnover (such as the skin or gut). In these tissues, ASCs are candidates because of their frequent cell divisions (compared to most ASCs) in conjunction with the long lifespan of ASCs. This combination creates the ideal set of circumstances for mutations to accumulate: mutation accumulation is the primary factor that drives cancer initiation. Evidence shows that the association represents an actual phenomenon, although specific cancers have been linked to a specific cause.[37][38]

De-differentiation of mutated cells may create stem cell-like characteristics, suggesting that any cell might become a cancer stem cell. In other words, a fully differentiated cell undergoes several mutations that drive it back to a stem-like state.

The concept of tumor hierarchy claims that a tumor is a heterogeneous population of mutant cells, all of which share some mutations, but vary in specific phenotype. A tumor hosts several types of stem cells, one optimal to the specific environment and other less successful lines. These secondary lines may be more successful in other environments, allowing the tumor to adapt, including adaptation to therapeutic intervention. If correct, this concept impacts cancer stem cell-specific treatment regimes.[39] Such a hierarchy would complicate attempts to pinpoint the origin.

CSCs, now reported in most human tumors, are commonly identified and enriched using strategies for identifying normal stem cells that are similar across studies.[40] These procedures include fluorescence-activated cell sorting (FACS), with antibodies directed at cell-surface markers and functional approaches including side population assay or Aldefluor assay.[41] The CSC-enriched result is then implanted, at various doses, in immune-deficient mice to assess its tumor development capacity. This in vivo assay is called a limiting dilution assay. The tumor cell subsets that can initiate tumor development at low cell numbers are further tested for self-renewal capacity in serial tumor studies.[42]

CSC can also be identified by efflux of incorporated Hoechst dyes via multidrug resistance (MDR) and ATP-binding cassette (ABC) Transporters.[41]

Another approach is sphere-forming assays. Many normal stem cells such as hematopoietics or stem cells from tissues, under special culture conditions, form three-dimensional spheres that can differentiate. As with normal stem cells, the CSCs isolated from brain or prostate tumors also have the ability to form anchor-independent spheres.[43]

CSCs have been identified in various solid tumors. Markers specific for normal stem cells are commonly used for isolating CSCs from solid and hematological tumors. Cell surface markers have proved useful for isolation of CSC-enriched populations including CD133 (also known as PROM1), CD44, CD24, EpCAM (epithelial cell adhesion molecule, also known as epithelial specific antigen, ESA), THY1, ATP-binding cassette B5 (ABCB5),[44] and CD200.

CD133 (prominin 1) is a five-transmembrane domain glycoprotein expressed on CD34+ stem and progenitor cells, in endothelial precursors and fetal neural stem cells. It has been detected using its glycosylated epitope known as AC133.

EpCAM (epithelial cell adhesion molecule, ESA, TROP1) is hemophilic Ca2+-independent cell adhesion molecule expressed on the basolateral surface of most epithelial cells.

CD90 (THY1) is a glycosylphosphatidylinositol glycoprotein anchored in the plasma membrane and involved in signal transduction. It may also mediate adhesion between thymocytes and thymic stroma.

CD44 (PGP1) is an adhesion molecule that has pleiotropic roles in cell signaling, migration and homing. It has multiple isoforms, including CD44H, which exhibits high affinity for hyaluronate and CD44V which has metastatic properties.

CD24 (HSA) is a glycosylated glycosylphosphatidylinositol-anchored adhesion molecule, which has co-stimulatory role in B and T cells.

CD200 (OX-2) is a type 1 membrane glycoprotein, which delivers an inhibitory signal to immune cells including T cells, natural killer cells and macrophages.

ALDH is a ubiquitous aldehyde dehydrogenase family of enzymes, which catalyzes the oxidation of aromatic aldehydes to carboxyl acids. For instance, it has a role in conversion of retinol to retinoic acid, which is essential for survival.[45][46]

The first solid malignancy from which CSCs were isolated and identified was breast cancer and they are the most intensely studied. Breast CSCs have been enriched in CD44+CD24/low,[44] SP[47] and ALDH+ subpopulations.[48][49] Breast CSCs are apparently phenotypically diverse. CSC marker expression in breast cancer cells is apparently heterogeneous and breast CSC populations vary across tumors.[50] Both CD44+CD24 and CD44+CD24+ cell populations are tumor initiating cells; however, CSC are most highly enriched using the marker profile CD44+CD49fhiCD133/2hi.[51]

CSCs have been reported in many brain tumors. Stem-like tumor cells have been identified using cell surface markers including CD133,[52] SSEA-1 (stage-specific embryonic antigen-1),[53]EGFR[54] and CD44.[55] The use of CD133 for identification of brain tumor stem-like cells may be problematic because tumorigenic cells are found in both CD133+ and CD133 cells in some gliomas and some CD133+ brain tumor cells may not possess tumor-initiating capacity.[54]

CSCs were reported in human colon cancer.[56] For their identification, cell surface markers such as CD133,[56] CD44[57] and ABCB5,[58] functional analysis including clonal analysis [59] and Aldefluor assay were used.[60] Using CD133 as a positive marker for colon CSCs generated conflicting results. The AC133 epitope, but not the CD133 protein, is specifically expressed in colon CSCs and its expression is lost upon differentiation.[61] In addition, CD44+ colon cancer cells and additional sub-fractionation of CD44+EpCAM+ cell population with CD166 enhance the success of tumor engraftments.[57]

Multiple CSCs have been reported in prostate,[62]lung and many other organs, including liver, pancreas, kidney or ovary.[45][63] In prostate cancer, the tumor-initiating cells have been identified in CD44+[64] cell subset as CD44+21+,[65] TRA-1-60+CD151+CD166+[66] or ALDH+[67] cell populations. Putative markers for lung CSCs have been reported, including CD133+,[68] ALDH+,[69] CD44+[70] and oncofetal protein 5T4+.[71]

Metastasis is the major cause of tumor lethality. However, not every tumor cell can metastasize. This potential depends on factors that determine growth, angiogenesis, invasion and other basic processes.

In epithelial tumors, the epithelial-mesenchymal transition (EMT) is considered to be a crucial event.[72] EMT and the reverse transition from mesenchymal to an epithelial phenotype (MET) are involved in embryonic development, which involves disruption of epithelial cell homeostasis and the acquisition of a migratory mesenchymal phenotype.[73] EMT appears to be controlled by canonical pathways such as WNT and transforming growth factor .[74]

EMT's important feature is the loss of membrane E-cadherin in adherens junctions, where -catenin may play a significant role. Translocation of -catenin from adherens junctions to the nucleus may lead to a loss of E-cadherin and subsequently to EMT. Nuclear -catenin apparently can directly, transcriptionally activate EMT-associated target genes, such as the E-cadherin gene repressor SLUG (also known as SNAI2).[75] Mechanical properties of the tumor microenvironment, such as hypoxia, can contribute to CSC survival and metastatic potential through stabilization of hypoxia inducible factors through interactions with ROS (reactive oxygen species).[76][77]

Tumor cells undergoing an EMT may be precursors for metastatic cancer cells, or even metastatic CSCs.[78] In the invasive edge of pancreatic carcinoma, a subset of CD133+CXCR4+ (receptor for CXCL12 chemokine also known as a SDF1 ligand) cells was defined. These cells exhibited significantly stronger migratory activity than their counterpart CD133+CXCR4 cells, but both showed similar tumor development capacity.[79] Moreover, inhibition of the CXCR4 receptor reduced metastatic potential without altering tumorigenic capacity.[80]

In breast cancer CD44+CD24/low cells are detectable in metastatic pleural effusions.[44] By contrast, an increased number of CD24+ cells have been identified in distant metastases in breast cancer patients.[81] It is possible that CD44+CD24/low cells initially metastasize and in the new site change their phenotype and undergo limited differentiation.[82] The two-phase expression pattern hypothesis proposes two forms of cancer stem cells - stationary (SCS) and mobile (MCS). SCS are embedded in tissue and persist in differentiated areas throughout tumor progression. MCS are located at the tumor-host interface. These cells are apparently derived from SCS through the acquisition of transient EMT (Figure 7).[83]

CSCs have implications for cancer therapy, including for disease identification, selective drug targets, prevention of metastasis and intervention strategies.

Somatic stem cells are naturally resistant to chemotherapeutic agents. They produce various pumps (such as MDR[citation needed]) that pump out drugs and DNA repair proteins. They have a slow rate of cell turnover (chemotherapeutic agents naturally target rapidly replicating cells).[citation needed] CSCs that develop from normal stem cells may also produce these proteins, which could increase their resistance towards chemotherapy. The surviving CSCs then repopulate the tumor, causing a relapse.[84]

Selectively targeting CSCs may allow treatment of aggressive, non-resectable tumors, as well as prevent metastasis and relapse.[84] The hypothesis suggests that upon CSC elimination, cancer could regress due to differentiation and/or cell death.[citation needed] The fraction of tumor cells that are CSCs and therefore need to be eliminated is unclear.[85]

Studies looked for specific markers[17] and for proteomic and genomic tumor signatures that distinguish CSCs from others.[86] In 2009, scientists identified the compound salinomycin, which selectively reduces the proportion of breast CSCs in mice by more than 100-fold relative to Paclitaxel, a commonly used chemotherapeutic agent.[87] Some types of cancer cells can survive treatment with salinomycin through autophagy,[88] whereby cells use acidic organelles such as lysosomes to degrade and recycle certain types of proteins. The use of autophagy inhibitors can kill cancer stem cells that survive by autophagy.[89]

The cell surface receptor interleukin-3 receptor-alpha (CD123) is overexpressed on CD34+CD38- leukemic stem cells (LSCs) in acute myelogenous leukemia (AML) but not on normal CD34+CD38- bone marrow cells.[90] Treating AML-engrafted NOD/SCID mice with a CD123-specific monoclonal antibody impaired LSCs homing to the bone marrow and reduced overall AML cell repopulation including the proportion of LSCs in secondary mouse recipients.[91]

A 2015 study packaged nanoparticles with miR-34a and ammonium bicarbonate and delivered them to prostate CSCs in a mouse model. Then they irradiated the area with near-infrared laser light. This caused the nanoparticles to swell three times or more in size bursting the endosomes and dispersing the RNA in the cell. miR-34a can lower the levels of CD44.[92][93]

The design of new drugs for targeting CSCs requires understanding the cellular mechanisms that regulate cell proliferation. The first advances in this area were made with hematopoietic stem cells (HSCs) and their transformed counterparts in leukemia, the disease for which the origin of CSCs is best understood. Stem cells of many organs share the same cellular pathways as leukemia-derived HSCs.

A normal stem cell may be transformed into a CSC through disregulation of the proliferation and differentiation pathways controlling it or by inducing oncoprotein activity.

The Polycomb group transcriptional repressor Bmi-1 was discovered as a common oncogene activated in lymphoma[94] and later shown to regulate HSCs.[95] The role of Bmi-1 has been illustrated in neural stem cells.[96] The pathway appears to be active in CSCs of pediatric brain tumors.[97]

The Notch pathway plays a role in controlling stem cell proliferation for several cell types including hematopoietic, neural and mammary[98] SCs. Components of this pathway have been proposed to act as oncogenes in mammary[99] and other tumors.

A branch of the Notch signaling pathway that involves the transcription factor Hes3 regulates a number of cultured cells with CSC characteristics obtained from glioblastoma patients.[100]

These developmental pathways are SC regulators.[101] Both Sonic hedgehog (SHH) and Wnt pathways are commonly hyperactivated in tumors and are necessary to sustain tumor growth. However, the Gli transcription factors that are regulated by SHH take their name from gliomas, where they are highly expressed. A degree of crosstalk exists between the two pathways and they are commonly activated together.[102] By contrast, in colon cancer hedgehog signalling appears to antagonise Wnt.[103]

Sonic hedgehog blockers are available, such as cyclopamine. A water-soluble cyclopamine may be more effective in cancer treatment. DMAPT, a water-soluble derivative of parthenolide, induces oxidative stress and inhibits NF-B signaling[104] for AML (leukemia) and possibly myeloma and prostate cancer. Telomerase is a study subject in CSC physiology.[105] GRN163L (Imetelstat) was recently started in trials to target myeloma stem cells.

Wnt signaling can become independent of regular stimuli, through mutations in downstream oncogenes and tumor suppressor genes that become permanently activated even though the normal receptor has not received a signal. -catenin binds to transcription factors such as the protein TCF4 and in combination the molecules activate the necessary genes. LF3 strongly inhibits this binding in vitro, in cell lines and reduced tumor growth in mouse models. It prevented replication and reduced their ability to migrate, all without affecting healthy cells. No cancer stem cells remained after treatment. The discovery was the product of "rational drug design", involving AlphaScreens and ELISA technologies.[106]

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Cancer stem cell - Wikipedia

Connecticut & New England Stem Cell Injection Therapy …

Valley Sports Physicians is a national leader and pioneer in the use of Stem Cell Injections for orthopedic and musculoskeletal conditions.

Dr. Tortland began performing stem cell injections in 2008, the first in New England and longer than most in the country. Few have as much experience in the field of Stem Cell Therapy for orthopedic and musculoskeletal conditions.

Stem Cells have several unique abilities. They can transform into other cell types, such as bone, cartilage, muscle and tendon. And they also serve an important signaling functioning, recruiting other stem cells to the target area and triggering nearby cells to begin the repair process.

At Valley Sports Physicians we use Stem Cells most commonly to treat the following conditions:

While the use of stem cells is gaining in popularity, its important to realize that not all stem cell treatments are the same. How the stem cells are obtained, and how they are processed both can have a major impact on effectiveness. In addition, even the best stem cell products will be minimally effective if not administered properly. At Valley Sports Physicians we use the latest technology to harvest your stem cells to insure the highest quality product. We also perform all of our injections under direct ultrasound guidance; Dr. Tortland is an internationally recognized expert in ultrasound-guided injections. So you can be assured of the safest, most accurate treatment.

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Connecticut & New England Stem Cell Injection Therapy ...

Stem Cell Treatment – Robert Daley M.D.

Stem Cell Treatment with Dr. Daley

As we age, our bodies go through wear and tear from sports, jobs, and previous injuries. Joints and tendons absorb the bulk of the abuse and unfortunately these tissues have limited ability to heal.

Joints often develop Osteoarthritis (OA), which is a destruction of the cartilage, which is the protective tissue of the joint. Once the cartilage is too thin or gone, bones rub together and cause pain. Unfortunately, OA is most common in the joints we use the most such as the knees.

Dr. Daley is among a select group of physicians around the country to offer Stem Cell treatment to relieve knee osteoarthritis (OA) pain and chronic tendonitis. Patients can benefit from a unique non-surgical procedure using the patients own stem cells for injections or surgical implantation of those cells. This treatment uses your own bodys repair mechanisms and growth factors to promote healing.

How can stem cells help me heal?

Adult stem cells have been helping your body heal your whole life. Your body naturally wants to help itself and most of the time it does. Unfortunately, there are some injuries that have a harder time healing especially as we get older. Taking a rich source of your own stem cells and concentrating them can enhance the healing capacity of your own body.

Where do adult stem cells reside in the body?

Stem cells reside in many tissues throughout your body, but the richest sources are found in your bone marrow. Fortunately, bone marrow can be harvested from several bones within your body and is relatively easy to access. Dr. Daley may choose to harvest cells from your bone marrow to treat your chronic knee pain.

Will the procedure regenerate cartilage in my joint?

There is some limited data suggesting an ability to regenerate cartilage in joints, but it also appears that whether or not the cartilage regenerates has little correlation with relief of pain. If there is significant spurring and significant loss of the joint space, there is little chance of cartilage regeneration.

During the procedure, Dr. Daley withdraws some blood from your bone, which contains stem cells from the bone marrow. This can be obtained from the hip or knee. The technique is fast and efficient, but most importantly provides a way to harness your bodys most powerful regenerative cells. The stem cells are then either injected or surgically implanted into the patients damaged joint. The stem cells are from the patients own body so the risk of rejection is very low.

Does the treatment consist of one injection or multiple injections?

Typically we do one stem cell injection, followed up 6 weeks later with a platelet rich plasma injection (blood drawn from your arm). If you are coming from out of town, this will be taken into consideration and may be modified. Our protocol is continually evolving, so this is ultimately decided on a case-by-case basis.

What is the success rate of a Stem Cell injection?

Experience has suggested most patients will have significant relief of pain around 1-2 months post injection. This will often continue to improve for the first 3-6 months after the stem cell procedure. There are patients who will not get any improvement at all from this procedure, probably around 10-20%. This is still a new treatment, and thus there are not a lot of long-term outcomes studies completed so far.

How do I know if I am a candidate?

Stem cell implantation may be recommended for patients with osteoarthritis of the knee. Typically these patients have failed other treatment options including rest, medications, other injections and physical therapy and are not anxious for total knee replacement.

Who is not a candidate for Stem Cells?

What are the risks?

The cells used in your treatment are your own cells. The processing of the bone marrow is only to remove the unwanted cells and concentrate the wanted cells. This is done in a sterile device approved to centrifuge bone marrow. You probably will experience some discomfort during the bone marrow aspiration and the treatment, which may persist for a few days. Your doctor will do everything possible to minimize pain. Be sure to ask your doctor any questions you may have.

Before the Procedure:

After the Procedure:

Can I fly / drive home that day?

If you are flying (and you are not the pilot), you may fly home the same day, but there will be increased pain/discomfort after the procedure. If you are driving, you should have a driver, as there can be some mild to moderate discomfort in the first few hours following the procedure.

Stem Cell therapy is typically not covered by your insurance company. If you decide you want to explore this treatment option, you will first speak with one of our financial counselors. They assist you in determining if your insurance will pay for this procedure or if you will need to pay out of pocket for the treatment.

What should I do if I think Im a candidate?

If you live near one of Dr. Daleys offices in Hinsdale, New Lenox, or Joliet Illinois, we recommend scheduling an appointment for a consultation so that he can look at your radiology films (x-rays) and examine you to determine if you are a good candidate or not.

If you live more than 2-3 hours away, please work with your local health care professional to send us the following.

Send your images and records to us for review please include your name, address, phone number and email address. We will contact you with our recommendation within 7-10 business days of receiving your records.

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Stem Cell Treatment - Robert Daley M.D.

Woman grows a nose on her spine after experimental stem …

A female patient in the US has grown a nose on her back following a failed experimental stem cell treatment that was intended to cure her paralysis. The nose-like growth, which was producing a thick mucus-like material, has recently been removed as it was pressing painfully on herspine. If you ever needed an example of the potential perils of stem cell therapy, and just how little we actually know about the function of stem cells, this is it. Its also notable that this stem cell therapy was carried out in a developed country, as part of an approved trial (apparently unwanted growths are more common in developing nations with less stringent medical safeguards).

Eight years ago, olfactory stem cells were taken from the patients nose and implanted in her spine. The stem cells were meant to turn into nerve cells that would help repair the womans spine, curing her of paralysis. Instead, it seems they decided to do what they were originally meant to do and attempt to build a nose. Over a number of years, the nose-like growth eventually became big enough and nosy enough to cause pain and discomfort to the patient. As reported by New Scientist, surgeons removed a 3-centimetre-long growth, which was found to be mainly nasal tissue, as well as bits of bone and tiny nerve branches that had not connected with the spinal nerves. [DOI: 10.3171/2014.5.SPINE13992 Autograft-derived spinal cord mass following olfactory mucosal cell transplantation in a spinal cord injury patient]

Your olfactory system. 1 is the olfactory bulb (the bit of your brain that processes smells); 6 is the olfactory receptors that bind to specific chemicals (odors). [Image credit: Wikipedia]

What went wrong, then? Basically, at the top of your nasal passages there is the olfactory mucosa. This region contains all of the machinery for picking up odors, and the neurons for sending all of that data off to your brains olfactory bulb for processing. Cells from this region can be easily and safely harvested, and with the correct processing they behave just like pluripotent embryonic stem cells that can develop into many other cell types. These olfactory stem cells could develop into cartilage, or mucus glands, or neurons. The researchers obviously wanted the latter, to cure the patients spinal nerve damage but seemingly they got it wrong, and thus she sprouted a second nose. Moving forward, newer olfactory stem cell treatments have an isolation stage to prevent this kind of thing from happening. [Read:The first 3D-printed human stem cells.]

Its important to note that medicine, despite being carried out primarily on humans, is still ultimately a scientific endeavor that requires a large amount of trial and error. In the western world, its very, very hard to get a stem cell therapy approved for human trials without lots of animal testing. Even then, the therapies are often only used on people who have nothing to lose. Obviously its hard to stomach news like this, and Im sure that stem cell critics will be quick to decry the Frankensteinian abomination created by these scientists. But when you think about the alternative no advanced medicine and significantly reduced lifespans for billions of people then really, such experimental treatments are nothing to sneeze at.

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Woman grows a nose on her spine after experimental stem ...

Center for Cell Reprogramming | Georgetown University

In the Spotlight

National Press Foundation Visits the Center for Cell Reprogramming January 2016 Members of the National Press Foundation gathered this past January to Georgetown University Medical Center and the Center for Cell Reprogramming. While here they visited the CCR labs and experienced a personal tour from Director, Dr. Richard Schlegel.

A Bed of Mouse Cells Helps Human Cells Thrive In the Lab January 7, 2015 Dr. Richard Schlegel speaks with Richard Harris, NPR, to talk about using his groundbreaking techniques in cell reprogramming to test artemisinin-a drug commonly used to treat malaria-to kill cervical cancer cells.

Medical Center Researchers Named National Academy of Inventors Fellows December 16, 2014 Dr. Richard Schlegel has been named one of the2014 Fellows of the National Academy of Inventors (NAI) for his groundbreaking discovery of the HPV vaccine. Read how the technology he co-developed hashelped drop HPV infectionsby 56 percent in the US, according to the American Cancer Society.

Researchers Test Cancer Treatments on Patients Own Cells November 13, 2014 Dr. Richard Schlegel is quoted in The Boston Globe'snews story which highlights research recently publishedby Dr. Jeff Engelman,Directorof Thoracic OncologyatMassachusetts General Hospital. Dr. Engelmanco-led a group of physicians and researchers towards new steps in personalized cancer treament using technology invented by Dr. Schlegel.

Research & Innovation at Georgetown University Medical Center August 14, 2014 Dr. Richard Schlegel was recently featured in Georgetown University Medical Center's video about groundbreaking research and how it is affecting lives within and outside the GUMC community.

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Center for Cell Reprogramming | Georgetown University

Storing Stem Cells In Teeth For Your Familys Future Health

Protect your family's future health.

Secure their stem cells today.

Bank the valuable stem cells found in

baby teeth and wisdom teeth.

Researchers at the National Institutes of Health (NIH) discovered a rich source of adult stem cells in teeth the stem cells that naturally repair your body. Scientists aredirecting stem cells so they grow into almost any type of human cell, including heart, brain, nerve, cartilage, bone, liver and insulin producing pancreatic beta cells.

AAOMS - American Association of Oral and Maxillofacial Surgeons

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Doctors recommend StemSave stem cell banking for the cryopreservation of powerful adult stem cells from deciduous teeth (baby teeth), wisdom teeth or permanent teethwith healthy dentalpulp.

Easy OnlineEnrollment

StemSave Stem Cell Banking exclusively recovers and stores non-embryonic stem cells. Dental Stem Cells are also known asDSC, DASC, DPSC, or SHED cellsand are classified as atype of adult stem cells.

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Storing Stem Cells In Teeth For Your Familys Future Health

Adult Stem Cell Banking Information from Celltex Therapeutics

Why Bank?

Not everyone interested in adult stem cell therapy has a condition that requires immediate treatment. Indeed, some far-sighted individuals would like to have a large reserve of their own stem cells available in case they are needed in the future. Celltex can provide state-of-the-art adult stem cell banking services that can provide individuals peace of mind.

No matter where you live, Celltex will work with you to provide banking services for your stem cells.

Sometimes your body cannot create enough stem cells to make an effective healing response to an illness or injury. Banking your cells now provides the opportunity to multiply and utilize your younger, healthy cells at a later point in life when you and your physician determine it would be beneficial.

Whether you choose to bank because of a current condition, or so that your cells are available to you in case of an emergency, illness, injury, or accident in the future, there are numerous benefits to banking your stem cells now. It is a simple and safe procedure that can benefit you now, or in the future.

As we age, illness and the natural processes of aging reduce the number of stem cells available to regenerate organs, muscles and bone and in particular we have fewer adult cells that have the collective power to assist in healing many different kinds of cells.

The younger you are when you bank your cells, the more efficient, active and mobile they are.

Celltex is a leader in providing services for the rapidly expanding field of regenerative medicine. Specifically, Celltex precisely separates, multiplies, and stores adult adipose-derived mesenchymal stem cells for autologous use by physicians. This means that an individuals fat (adipose) is the source of their adult stem cells, which are used only for that individual and never for any other person.

Celltexs advanced laboratory uses a patented process to ensure that it supplies physicians with genetically identical, autologous adult stem cells for clinical therapeutic use. Dedicated to ensuring the proper extraction, isolation and culture of stem cells, we hold more than 14 patents protecting our methodology and quality control processes that ensure the potency and purity of your cells when you choose to use them.

No other corporation or academic organization engaged in the banking of adult stem cells does as much quality control or in as secure an environment as that deployed by Celltex. This is the leading edge of biosafety applied to regenerative medicine.

Celltex does not treat patients or provide any healthcare services. Rather, individual doctors decide whether a patient their patient might benefit from adult stem cells.

Below is an overview of the process to bank your adult stem cells:

Read more about Celltex stem cell banking services for adults, for families, or for groups and companies.

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Adult Stem Cell Banking Information from Celltex Therapeutics

Embryonic Stem Cell Research Threatened – Hartford Courant

More than any other scientific field, with the possible exception of climate change, embryonic stem cell research is subject to the ups and downs of politics and trouble may lie ahead for scientists in Connecticut and across the country.

Derived from early embryos, embryonic stem cells can become any cell in the body. Since the discovery of human embryonic stem cells in 1998, scientists have explored their potential use as therapies for diseases and injuries. Embryonic stem cell derivatives, for example, could replace the pancreatic cells lost in Type I Diabetes or the neurons lost in Parkinson's Disease. But just as this approach begins to show promise, a new threat appears on the horizon.

U.S. Rep. Tom Price, R-Ga., Donald Trump's nominee to head the Department of Health and Human Services with oversight over the National Institutes of Health, is on record opposing embryonic stem cell research. As stem cell researchers, we fear that this appointment would endanger human embryonic stem cell research in the United States and reverse the substantial progress made in recent years. There are promising clinical trials underway for macular degeneration, spinal cord injury and diabetes with more possible, including for Parkinson's disease.

Connecticut has recognized the importance of human embryonic stem cell research and funded first the Connecticut Stem Cell Program, and now the Regenerative Medicine Research Fund. This brought Connecticut to the forefront of stem cell research. Continued support at the national level is also needed, however, if we wish to continue making progress toward effective cell-based therapies.

What makes this field of research so controversial is that an early stage human embryo (five days after fertilization) called a blastocyst is used to produce a human embryonic stem cell line. Federal funds may not be used to produce a new human embryonic stem cell line becausethe money cannot supportresearch that directly uses human embryos. At this point, however, federal funds can be used to work on human embryonic stem cells. Despite this, a minority in the government strive to further limit federal funding so that it cannot be used even for studies on lines generated using alternative financial sources.

Many claim we can achieve our therapeutic goals using other stem cell sources, but as stem cell scientists we are keenly aware of the limitations of these alternatives.

Adult stem cells, which have limited capacity for generating the high number of cells needed for human transplants and can only produce certain cell types, will likely work for some applications, but not others.

Another type of stem cell, induced pluripotent stem cells, can be generated from adult cell types such as skin, without the need to start with a human embryo. These cells share many properties with embryonic stem cells, including the ability to become virtually any cell in the body. Work using these cells has exploded since their discovery 10 years ago. Induced pluripotent stem cells are useful for modeling human disease in a culture dish and for drug screening. For clinical application, however, these cells have several limitations. Virtually all the cell lines made to date are genetically modified, and this modification could potentially cause cancer, which precludes their use in humans. Most important, as described by many stem cell researchers, embryonic stem cells behave most consistently and therefore remain the gold standard against which other research is compared.

While this is not the place for a full discussion of the moral status of early human embryos, it is worth making some observations. The blastocyst forms 5 days after fertilization, prior to implantation in the uterus, and consists of a couple of hundred cells. All human embryonic stem cell lines that are approved for federally funded research are derived from blastocysts leftover from infertility treatment, with the informed consent of the donors. The alternative futures for these embryos are to be kept frozen indefinitely or to be destroyed. Given these options, many would agree that a future of producing a cell line that could eventually reduce suffering and save lives is a preferred fate.

The United States is a leader in embryonic stem cell research, from basic science to clinical application. This achievement has been fueled by successful collaborations between government-funded academic laboratories and the private sector. A skilled workforce and state-of-the-art infrastructure has been established. New restrictions could well lead to a brain drain and likely provide a serious roadblock to numerous cures.

Laura Grabel, Ph.D., is the Lauren B. Dachs Professor of Science and Society and a professor of Biology at Wesleyan University and president of the Connecticut Academy of Science and Engineering. Diane Krause, MD, Ph.D., is a professor at the Yale School of Medicine, associate director of the Yale Stem Cell Center, and director of the Clinical Stem Cell Processing Laboratory.

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Embryonic Stem Cell Research Threatened - Hartford Courant

induced pluripotent stem cells – eurostemcell.org

An important step in developing a therapy for a given disease is understanding exactly how the disease works: what exactly goes wrong in the body? To do this, researchers need to study the cells or tissues affected by the disease, but this is not always as simple as it sounds. For example, its almost impossible to obtain genuine brain cells from patients with Parkinsons disease, especially in the early stages of the disease before the patient is aware of any symptoms. Reprogramming means scientists can now get access to large numbers of the particular type of neurons (brain cells) that are affected by Parkinsons disease. Researchers first make iPS cells from, for example, skin biopsies from Parkinsons patients. They then use these iPS cells to produce neurons in the laboratory. The neurons have the same genetic background (the same basic genetic make-up) as the patients own cells. Thus scientist can directly work with neurons affected by Parkinsons disease in a dish. They can use these cells to learn more about what goes wrong inside the cells and why. Cellular disease models like these can also be used to search for and test new drugs to treat or protect patients against the disease.

iPS cells - derivation and applications:Certain genes can be introduced into adult cells to reprogramme them. The resulting iPS cells resemble embryonic stem cells and can be differentiated into any type of cell to study disease, test drugs or-after gene correction-develop future cell therapies

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induced pluripotent stem cells - eurostemcell.org

Induced Pluripotent Stem Cell Repository | California’s …

The Induced Pluripotent Stem Cell (iPSC) Repository is a major effort from CIRM to create a collection of stem cells developed from thousands of individuals.

CIRM is creating the iPSC bank so that scientists can use the cells, either in a petri dish or transplanted into animals, to study how disease develops and progresses and develop and test new drugs or other therapies. The iPSC bank is now open and cell lines are available at catalog.coriell.org/CIRM.

The large size of the collection will provide researchers with a powerful tool for studying genetic variation between individuals, helping scientists understand how disease and treatment may vary in a diverse population like Californias.

What is the iPSCRepository? How does it work? Why iPS cells? Who is generating the cells? Which diseases will be represented? How many samples are being collected for each condition?

What is the iPSCRepository? The Human Induced Pluripotent Stem Cell (hiPSC) Repositoryis one of the California stem cell agencys major efforts to provide valuable resources to the research community. The goal is to create a bank of high quality stem cell lines developed from thousands of individuals for use in research.

How does it work? Blood or skin samples collected from approximately 3,000 individuals will be turned into stem cell lines. These lines will be made available to researchers throughout California and around the world.

Why iPS cells? iPS cells are generated from cells easily obtained from living humans, i.e. blood or a small piece of skin; they have unlimited expansion potential in the petri dish, so huge numbers of cells can be generated for research studies or drug development; and they can be coaxed into the types of cells affected in various diseases, such as heart or brain disorders. This provides an unprecedented opportunity to study the cell types from patients that are affected in disease but cannot otherwise be easily obtained in large quantities from them.

Who is generating the cells? Seven clinician scientists from four California institutions recruit tissue donors who suffer from one of the included diseases or are healthy controls. Some blood or a small piece of skin is collected from those donors, and these samples are shipped to the company Cellular Dynamics International (CDI). CDI generates iPS cells from the samples, and then transfers the iPS cells to the Coriell Institute for Biomedical Research. Coriell operates a cell bank that will distribute the iPS cells to interested researchers at academic and other non-profit institutions, and also to pharmaceutical companies that may want to use them to find new drugs for the diseases that are included in this bank. While CDI and Coriell are located outside California, they have set up facilities at the Buck Institute in Novato, CA, where they generate and bank the iPS cells for this Initiative.

Which diseases will be represented? The stem cell lines created will represent a variety of diseases or conditions that affect brain, heart, lung, liver or eyes. Grantees come from a variety of California-based institutions:

How many samples are being collected? Below is a table that outlines CIRM's collection goalsfor each condition, along with control samples.

* these control donors will be specifically tested for the absence of lung disease

CIRM's New Stem Cell Bank Up, Running (California Healthline)

iPSC Repository Brochure [PDF] Stem Cell FAQ How do scientists model disease with iPSC's

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Induced Pluripotent Stem Cell Repository | California's ...