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Stem Cell Therapy

Stem cell therapy is often referred to as the future of medicine, with complex medical jargon

making many believe that such treatments are still only theoretical. However, several stem cell

therapies are already routinely used to treat diseases such as leukaemia, other types of cancer,and blood disorders. Adult stem cell transplants have actually been used to treat leukaemiathrough bone marrow stem cell transplant for more than forty years, with significantdevelopments in stem cell harvesting, culturing, and storage techniques having taken placeduring this time. As stem cell technologies have progressed, the need for actual bone marrowharvesting has reduced. A variety of pharmaceuticals have been developed which encouragebone marrow stem cells to enter systemic circulation; patients may then use stem cells sourcedfrom their own blood through a process called apheresis to repopulate their bone marrow afterchemotherapy.

The easier access to stem cells afforded by peripheral blood stem cell harvesting has also been

aided by the discovery of stem cells in umbilical cord blood, the skin, adipose (fat) tissue, andother stem cell niches in the body. Stem cell therapy using cord blood transplant is also likely toincrease as more parents donate cord blood to national blood banks and as scientists havedeveloped ways of increasing the yield of stem cells from cord blood previously thoughtinsufficient to treat fully grown adults. People from minority racial and ethnic groups are beingparticularly encouraged to donate cord blood as this source of stem cells can be used for a widernumber of people due to lower risks of immune system rejection compared to adult bonemarrow. A $48 million funding initiative by the Canadian government to create a national stemcell bank for use in transplants is also likely to increase the number of people receiving stem celltherapy as a routine procedure for certain types of cancer and blood disorders as well as providevaluable material for stem cell research when donated blood is unsuitable for transplant itself.

Stem cell therapy may not be direct infusion of stem cells themselves into a patients blood or

organs, but could involve the use of treatments which influence the activity of those stem cellsalready present in their body in order to encourage regeneration. Stem cells may also be used togrow new tissue in the laboratory in order to be transplanted into the patient from whom the stemcells originally came, thus removing the risk of graft versus host disease and eliminating the needto wait for a donor to be available. Such techniques already exist, with pancreatic cells havingbeen created, along with dopaminergic cells, and liver cells, for example, although all of theserequire considerably more research prior to being used to generate new organs or tissue for thosewith diabetes, Parkinsons Disease, or liver disease.

Gerons stem cell therapy makes use of the embryonic stem cells ability to create all of the cell

types in the body including nerve cells. Scientists have, however, found that adult neural stemcells exist and appear to be a promising source of stem cells when observed in stem cell therapyin animal models. The discovery of neural stem cells in the adult brain, and the ability todifferentiate neural stem cells from adipose tissue taken from the patient themselves offersenormous potential for developing stem cell therapy for multiple sclerosis and other neurologicalconditions such as Parkinsons Disease, Alzheimers Disease, Amyotrophic Lateral Sclerosis,and many others. Such stem cell therapy is a long way away from becoming standard practice


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however, as years of research into safety, efficacy, dosage, and comparison to current treatmentswill first be required. Trials into stem cell therapy for MS, diabetes, and SCI are currentlyrecruiting, and many more are likely to follow, with this providing perhaps the best opportunityfor patients who have had little success with conventional medical treatments.

Using Adult Stem Cells in Therapy

Recent discoveries regarding the location and behaviour of adult stem cells is particularlyexciting to researchers who have faced many years of limitations on their ability to investigatethe progression of particular diseases. Stem cell research in the laboratory can use stem cellstaken from patients with specific diseases to study the development of such diseases in a waythat has not been possible previously. Whilst this research may not lead to stem cell therapy forthe disease itself, it may allow researchers to develop other treatments on the basis of theevidence from the stem cell research and disease development. Pharmaceutical interventions toencourage specific activity of stem cells in a patient may be one form of future stem cell therapy.Indeed, a significant amount of recent research has focused on the effects on stem cells

proliferation and differentiation of gene expression and substances such as bone morphogenicprotein and fibroblast growth factor with possible clinical applications.

Cosmetic Stem Cell Therapy

Some stem cell therapies are available in the US for those undergoing reconstructive breastsurgery, breast augmentation, stem cell facelifts, or other cosmetic procedures. These stem cellprocedures are restricted and should only be carried out by those with adequate training andexperience; which is currently very few surgeons and doctors. The treatments are available dueto a loophole in current legislation which allows for minimally-processed stem cells taken fromthe patient themselves to then be transplanted back into the patient during the same procedure. In

this way there is little risk of complications such as graft versus host disease, or tumor growthfrom uncontrolled cell proliferation. However, such procedures have not been studied orapproved by the FDA and do still carry the usual risks of any surgical procedure, such asinfection, anaesthetic problems, and things such as nerve damage associated with the liposuctiontechniques commonly used to harvest the stem cells from adipose tissue. In many cases thetransplanted fat containing stem cells does not survive long after transfer, making the techniquesonly temporary, despite many unproven claims to the contrary.

Stem Cell Therapy Dangers

Recent research showing the recruitment of bone marrow mesenchymal stem cells into breasttissue in breast cancer also raises questions about the risks of moving stem cells into breasttissue, particularly where cancer stem cells may already exist. Long-term consequences of fat-relocation are unknown and the heavily marketed cosmetic procedures should be approachedwith caution. Similarly, stem cell therapy cream containing plant-derived stem cells is alsoheavily promoted but lacks any legitimate evidence of effect. A drink containing plant stem cellsfrom ginseng was also launched in 2011 purporting to boost energy levels and encourage goodhealth but with no serious scientific evidence proving any effect of such an ingredient.


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Adult Stem Cells

Adult stem cells are self-renewing cells that can generate specific types of differentiated cells.They differ from embryonic stem cells in that they are usually limited to cell types within acertain category, such as cartilage, bone, and connective tissue, or blood-forming stem cells.Some researchers prefer to call adult stem cells tissue stem cells or somatic stem cells as they arealso present in foetal tissue which can lead to confusion. Self-renewal is defined as cell divisionwhere either one or both of the daughter cells is also a stem cell that retains the samedevelopmental capacity as the mother cell.


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The most heavily researched stem cells are those found in the blood and in the skin. However,adult stem cells have also been extracted from adipose (fatty) tissue, the liver, lungs, eyes,gastrointestinal tract, brain, heart, and blood vessels. Tissues which have a high rate of turnovertend to be those with a larger presence of adult stem cells, in contrast to neuronal tissue whicheither has a low turnover rate or does not turn over at all.

Adult stem cells do not however, allow continuous regeneration of damaged tissue. If this werethe case then the body would be unlikely to ever actually wear out. Instead, most adult stem

cells are fairly inactive and researchers are frantically scrambling for answers regarding theactivation of these stem cells in order to treat or cure disease and pathology. The main potentialuses of adult stem cells are centered on helping us understand basic biological mechanisms,improving organ and tissue health by promoting cell growth and differentiation, and regeneratingold or damaged tissues. The apparently limited life-span of adult stem cells is presumeddependent on a number of factors such as accumulated DNA damage, oxidative stress fromreactive oxygen species, aberrant changes in gene expression, the attrition of telomeres, anddamage to the stem cell niche (protective area) with age.

Adult Stem Cell Research

Research has been conducted on adult stem cells for over forty years (compared to just twentyyears or so for embryonic stem cells). This means that adult stem cells are those most likely to beused in any stem cell treatment and such standard treatments as bone marrow transplants havebeen used for a considerable length of time. As adult stem cells appear more controllable interms of the cell types into which they differentiate when implanted in living tissue, they avoidsome of the risks of embryonic stem cells which scientists remain wary of due to their capacityto form any tissue in situ, even those undesirable.

A further advantage of adult stem cell use is that there is little ethical controversy around theextraction and use of adult stem cells. In the majority of cases the patient is able to give informedconsent for a procedure and knows the origin of the stem cells when an autologous or donor-matched transplant takes place. Some reports have surfaced of adult stem cells being able to doeverything that hESCs can; the research was found to be faulty however, and unable to bereplicated. The ability of scientists to reprogramme adult stem cells is increasing rapidly andsome success has been had in mimicking the human embryonic stem cells differentiation

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Location of Adult Stem Cells A Number of

Niches

A recent confirmation regarding adult stem cells is the location of an active population in thelimbus which maintains and regenerates the corneal epithelium. Suggested forty years ago, or so,by Davanger and Evansen (1971) as a possible site of stem cells, recent research has found thatthe limbal epithelial stem cells (LESCs) are highly active and have a long cell cycle. This makesthem ideal for transplant purposes and the relative transparency of the cornea also enables non-invasive imaging of the cells to be carried out. The LESCs are also thought to be held in anundifferentiated state by the pallisades of Vogt (folds in the sub-epithelial connective tissue).This protected enclave of stem cells has been termed a stem cell niche and there is speculation

over the existence in the body of other, as yet undiscovered, stem cell niches which could act asbountiful resources for stem cell extraction and stem cell therapy.

The use of LESCs has already helped restore a Canadian mans vision as he received a stem celltransplant from his sister after becoming almost completely blind due to a progressive eyedisease connected to contact lens use. The procedure, carried out in Toronto, is thought to be thefirst of its kind and may have removed the need for the man to have a corneal transplant. Morepatients are being scheduled for similar procedures and various visual problems may be helpedby this resource of stem cells. It is not yet possible to say whether the LESCs could be used totreat disorders outside of optical disease but some scientists remain optimistic over theirpotential.

Neural Cell RegenerationStem Cells and Markers

Another exciting development in the field of adult stem cell research is the finding that bonemarrow stem cells have the ability to travel to the brain post-transplant and can aidneuroregeneration. Scientists have conducted animal experiments using gender-mismatched bonemarrow transplants and then isolated neural cells which contained Y chromosomes in the brainsof those (female rodents) receiving the transplants. The possibility of using peripheral blood stem


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cells to form new neural tissue or regenerate damaged tissue is extremely exciting for thosesuffering with a degenerative brain illness, stroke patients, those with spinal cord injury, andmany others.

The identification of adult stem cells remains a complex issue with a number of strategies

employed by researchers but no general consensus on the best markers of adult stem cells. Moststem cell markers lack the desired specificity and cells outside of the stem cell zone underscrutiny may carry the same expression of these markers. An example of this is in the colonwhere CD44 and CD133, amongst others, have been suggested as markers of stem cells; theseoccur outside the area of stem cells however, making isolation difficult.

The Future of Adult Stem Cell Research

As scientists refine the methods of isolating, extracting, culturing, and reintroducing adult stemcells into the body the potential benefits for health appear almost limitless. With restrictionshaving been partially lifted on the funding of stem cell research using human embryonic stem

cells (hESCs) however, the future of adult stem cell research may start to look a little different.Other than bone marrow transplants, few clinical procedures using autologous stem cells areavailable in the US and other heavily-regulated countries. As clinical trials are underway usingadult stem cells for spinal cord injury treatment, stroke, cardiac problems, and a number of otherapplications, the next few years look likely to be full of stem cell treatment developmentsoffering possible hope for those with previously intractable diseases.

Embryonic Stem Cells

Unlike the various types of stem cell within the adult body, embryonic stem cells (hESCs) have

the capacity to differentiate into every type of cell and are considerably more active. Thesequalities led many researchers to believe, at least initially, that embryonic stem cells were theholy grail of regenerative medicine and that these cells would become the foundation oftreatments and therapies for previously incurable diseases. However, the ethical controversysurrounding stem cell research centers on hESCs, and there have been a variety of problems withthe cells themselves in terms of controlling their growth and proliferation when inserted intoliving tissue. As federal funding for stem cell research involving embryonic stem cells waseffectively halted for many years in the US, the focus of most scientists switched to adult stemcells as a source of potential treatments. Privately-funded research continued however, and theresulting information about hESCs is likely to be rapidly progressed now that federal fundinglegislation has relaxed slightly.

Embryonic Stem Cell Research and Blastocyst Death

Embryonic stem cells are responsible for creating every type of tissue in the body as theydevelop into a foetus at eight weeks. The blastocyst is the name given to the collection ofaround150 cells at 3-5 days after fertilization, with the inner cell mass of around 30 cellscontaining the pluripotent cells. These cells, taken from the interior cell cluster, invariablyresulted in the death of the blastocyst in early-stage embryonic stem cell research. The death of


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the embryo during this process became, therefore, the primary focus of many peoples ethicalopposition to embryonic stem cell research. However, in 2006, Lanza developed a techniquewhereby the inner pluripotent stem cells could be removed without destroying the blastocyst,which removed some of the concerns over hESC use.

Against Embryonic Stem Cell Research: Religious Opposition

Religious opposition to the use of human embryos in scientific research has come, for the mostpart, from various Christian organizations, with the Catholic Church, for example, viewing theembryo as a person with separate and recognizable rights and characteristics right from themoment of conception. No hESC research is, therefore acceptable by the Churchs doctrine.

Conversely, many Islamic and Jewish scholars view it as both acceptable, and indeed obligatory,to use any surplus embryos from in vitro fertilization procedures to attempt to find treatments forchronic and incurable disease.

The funding of embryonic stem cell research has to a large extent been constrained by the

conflation of Church and State in the US, despite many individual members of these religionsciting support for such research. For many, the subject is simply too complex to comprehendmaking people easily susceptible to polemics from both sides of the debate. This poorunderstanding and lack of intelligent critical debate also leaves potential patients bewildered asto their options for treatment with embryonic stem cells and may make them more easily targetedby overseas clinics offering false hope.

Embryonic Stem Cell Differentiation

Within the inner cell mass of an embryo are three distinct regions of stem cells including thecells which form the outermost layer. These cells go on to form the various cells of the nervoussystem, skin, sensory organs, and similar body structures, and are known as the ectoderm. Thosecells in the center of the inner cell mass are known as the mesoderm and form other tissues suchas the internal organs like the liver, and kidneys, along with muscle, connective tissue, and bone.
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The endoderm is the origin of the gastrointestinal tract and the lungs and relies on the mesodernto connect its structures to the ectoderm. These three layers of stem cells within the embryotogether form the more than 200 different cell types within the human adult body. They aretermed pluripotent, but are not totipotent as they cannot form the extraembryonic cells necessaryfor placental development or membranes formed in pregnancy.

Human embryonic stem cells rely on the presence of a number of transcription factors in order toremain pluripotent and prevent differentiation through gene signalling. These transcriptionfactors, such as Oct-4, Nanog, and Sox2 are being investigated for their potential to influence theplasticity of adult stem cells, making these multipotent stem cells more like pluripotentembryonic stem cells.

Embryonic Stem Cell Differentiation

The variability of embryonic stem cells to differentiate into any cell type has both advantagesand disadvantages for therapeutic applications and research. Whilst there is an increase in scope

of treating numerous diseases of many organs and tissues, the importance of controlling how theembryonic stem cells differentiate has been highlighted by individual cases where unwantedtissues have formed following the implantation of hESCs. There have been reports of patientswho underwent embryonic stem cell transplants for Parkinsons Disease and other neurological

conditions and who have subsequently developed bone, hair, and rapidly-expanding tumors inthe areas of the brain receiving the transplant. Uncontrolled and unregulated use of embryonicstem cells in clinics overseas presents a significant danger to patients who are unable to accesstreatment in the US, especially when the stem cells are injected directly into the brain byunqualified or inexperienced clinic staff.

Embryonic Stem Cell Research

Embryonic stem cell research has led to the development of therapeutic cloning, a practicewhereby an enucleated egg is combined with the somatic cell nucleus from the patient requiringa tissue transplant. The resulting embryo is then genetically matched to the patient themselvesand the embryonic stem cells can be harvested and cultured to generate tissues which face little,if any, risk of rejection by the patient upon transplantation. It is possible that embryonic germcells, found in the early germ cells which would form sperm and eggs, are pluripotent just likeembryonic stem cells and may offer another route by which patient-matched cell cultures andtissues could be created. Research on both of these techniques as possible therapeuticapplications is extremely limited and remains mostly theoretical however.

Approved Embryonic Stem Cell Treatments

There are no currently approved embryonic stem cell treatments although this may change in thenear future as the results of the first human trials of hESCs become available. In October, 2010,the first human medical trial using hESCs commenced, with researchers investigating theirpotential use for spinal cord injury patients (NCT01217008). This FDA-approved clinical trial byGeron, which is now on hold as the FDA investigates possible safety concerns, was followed byan approval in late November 2010 for Advanced Cell Technologys trial of hESC-derived


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retinal cells to treat patients with Stargardts Macular Dystrophy. This untreatable form of

juvenile macular degeneration develops between 10-20yrs old and eventually leads to blindness.The same Dr. Robert Lanza who discovered how to extract embryonic stem cells withoutdestroying the embryo is ACTs Chief Scientific Officer and said in a press release announcing

the trial that animal models had shown 100% improvement in visual performance over

untreated animals without any adverse effects. Near-normal function was achieved in these testsand the multicenter study is actively recruiting patients with Stargardts disease to take part inthis clinical trial which remains only one of two FDA-approved hESC trials at the time ofwriting. At the time of writing, there are no clinical trial results demonstrating the efficacy orsafety of human embryonic stem cells to treat any disease or condition and the number ofinduced-pluripotent adult stem cell trials currently underway may make some companies thinktwice before investing millions in controversial and problematic hESC research.

References

ACT Press Release: Advanced Cell Technology Receives FDA Clearance For the First Clinical

Trial Using Embryonic Stem Cells to Treat Macular Degeneration, November 22nd, 2010,http://j.mp/eNtApa

Geron Corporation: Safety Study of GRNOPC1 in Spinal Cord Injury (NCT01217008), Lastupdated March 2011, accessed athttp://j.mp/g84eQU

Stem Cells and Safety

teratoma with teeth - a danger of stem cell treatment

Making wide-ranging generalizations about the applicability of animal-based stem cell research,or even research on a select group of human patients is dangerous. Studies looking atautoimmune disorders, for example, have found that the down-regulation of autoimmune cells bymyeloablation and stem cell therapy may indeed aid a resetting of the immune system; they

also have implications for the self-regulated death of cancer cells, meaning that stem cell therapy
http://j.mp/g84eQUhttp://j.mp/g84eQUhttp://j.mp/g84eQUhttp://j.mp/g84eQU


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may inadvertently aid tumor growth in some patients. More research needs doing on this type ofreaction as it appears that the time of stem cell implantation has a major effect on the anti-cancer,and cancer-promoting effects of the treatments.

The use of embryonic stem cells in treatments has also come under fire due to the potential for

tumor growth after implantation. There have been a small number of reports of patients whotravelled to clinics in Israel, Germany, and China developing serious complications followingabnormal cell proliferation, tumor growth, or dysfunctional vascularity after stem cell treatmentsnot approved by regulators such as the FDA. Whilst it may sometimes seem that the FDA existspurely to antagonize patients wanting a promised cure for their illness made availableimmediately, the painstaking process of Phase I, II, and III trials is considerably safer thanallowing untested therapies to be used ad hoc.

References

John J. Pippin, M.D., F.A.C.C., The Need for Revision of Pre-Market Testing, The Failure of

Animal Tests of COX-2 Inhibitors, FDA Open Public Hearing, Arthritis Advisory Committee,Drug Safety and Risk Management Advisory Committee, February 17, 2005, http://j.mp/eZSmcF

Ivana Niki, Doron Merkler, Catherine Sorbara, Mary Brinkoetter, Mario Kreutzfeldt, FlorenceM Bareyre, Wolfgang Brck, Derron Bishop, Thomas Misgeld & Martin Kerschensteiner, Areversible form of axon damage in experimental autoimmune encephalomyelitis and multiplesclerosis, Nature Medicine online, 27 March.

Kimiskidis, V., Fassas, A., Sakellari, I., Kapinas, K.m Anagnostopoulos, A., Tsimourtou, V.,Sotirakoglou, K., Kazis, A., (2011), Long-term results of stem cell transplantation for MS,Neurology, Vol.76, no.12, pp.1066-1070.http://www.neurology.org/content/76/12/1066.full

Stem Cell Treatment

The Truth About Adult Stem Cell Treatment

The discovery of adult stem cell therapy has been a medical breakthrough because society hasdiscovered how effective this method is in assisting a number of diseases. Adult stem cells arederived from a number of biological sources such as: blood, umbilical cords, bone marrow,

muscle, placenta, fat, breast milk, dental pulp, and other sources. It has been found that theseadult stem cells act as the bodys natural healing cells which are why they are used to heal anumber of diseases that modern medicine is unable to remedy.
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The best part about using adult stem cells is that there are virtually zero side effects. It has beenused for over 40 years in the treatment of cancer, and research has shown that it has also beeneffective in the treatment of over 130 other diseases such as multiple sclerosis, autism, diabetes,and many other diseases and ailments.

What Exactly are Stem Cells and is Stem Cell Therapy for You?

Stem cells are a type of cell that can potentially develop into a variety of cell types within thebody, depending if they fall into the category of either pluripotent or multipotent stem cells.There is a significant difference in these types of cells: the first one can grow into almost anyother kind of cell within the body except the type of cell which is needed to support a fetus.

They can also develop into multipotent cells which serve as a type of repair system because aslong as the host is alive, these types of stem cells can divide infinitely as long as required torepair and replenish other cells. Once a stem cell has divided, it may either remain as is but italso has the ability to become another type of cell.

Stem cells are effective in treating disease because of their unique ability in developing supportto other cells in the body. They also work in our bodys tissues to repair any cells that need it.

Apart from just curing disease, stem cell treatments have been effective in pain management aswell as prevention. This makes stem cell treatment the most ideal and safe medical treatmentwhich everyone should consider using.

Stem Cell Types

Stem Cells from Embryos

Of the varieties, embryonic stem cells are the most controversial because the cells are harvestedfrom a live embryo which typically is destroyed after extracting the stem cells. Adult stem cells,the second type, are harvested from adult humans and therefore are less controversial andumbilical cord stem cells are harvested from umbilical cord blood and placenta shortly afterbirth.

Embryonic Stem Cells are harvested exclusively from early stage embryos and what makesthem so special is they can transform into all 200 plus types of cell tissue found in the body and

multiply indefinitely. That means embryonic stem cells can be used for many stem celltreatments including diabetes and Parkinsons disease. Unlike embryonic stem cells, adult stemcells are partially specialized because they are limited in cell tissue transformation. Umbilicalcord stem cells are fast becoming the most researched of stem cell types and have the potential tobe just as useful in treating diseases and conditions as embryonic stem cells.


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Spinal Cord Injury Recovery Paralyzed

Rats Walk Again

by Leigh Matthews on June 6, 2012

Patients with spinal cord injuries have been offered hope via a new study in Switzerland where

paralyzed rats walked again after treatment using electrical and chemical stimulation of the spinal cord

and robotic support. Fully restoring movement in complete spinal cord injury is unheard of, but are the

results of this study in rats as promising for spinal cord injury patients as many are making out, or are

stem cell treatments for spinal cord injury still promising?

From Paralysis to Athleticism

The team of scientists in Switzerland, at Ecole Polytechnique Federale de Lausanne, induced

spinal cord injury in rats by cutting through the spinal cord to cause severe paralysis. GregoireCourtine and his team then used the newly developed technique and observed the rats walkingand running after just a couple of weeks. The rats were once again able to climb stairs, avoidobstacles, run, walk, and behave as normal after the treatment.

SCI Repair Procedure

The study has taken five years to complete and the results have now been published in thejournal Science, allowing fellow spinal cord injury researchers to evaluate the therapy. Half of allhuman spinal cord injuries result in persistent paralysis and there is no treatment currentlyavailable to restore function although stem cell research has enjoyed some success. Theprocedure used in this trial involves an electrochemical neuroprosthesis and a robotic posturalinterface that the researchers designed to artificially support the rats desired movements. Thesupraspinal pathways disrupted by the spinal cord injury were then able to once again deliver therelevant signals from the central cortex to facilitate movements. In spinal cord injuries the cortexmaintains its ability to process and respond to information received but it is not able tocommunicate with the spinal cord and nerves below the level of injury. This technique reroutesthe signals around the injury site and uses chemicals to activate the dormant spinal cord. Thetherapy makes use of the nervous systems inherent ability to create new pathways.

Chemical Cocktails and SCIs

The Swiss team used chemicals that bind to dopamine, adrenaline, and serotonin receptors in thespinal cord mimicking the normal release of such neurotransmitters in a healthy spine. Afterinjecting these chemicals the rats had their spinal cord stimulated by implanted electrodes andthey were then taught how to walk again. Using a piece of chocolate as a lure, the rats weresupported by a specially created vest which suspended them upright and forced them to use theirback legs to move towards the food. The rats hind legs were paralyzed as a result of the spinal
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cord injury but after several days they took their first voluntary steps and gradually rebuilt nervefibers to create functional movement once again.

Gerons Spinal Cord Injury Research

Unfortunately, the most pioneering work done on stem cell research for spinal cord injury wasbeing conducted by Geron who closed their research last year to concentrate on other researchventures. Their successes in treating rats with stem cells for spinal cord injuries were welldocumented and the hope is that others will take up the mantle to continue the work. This newstudy suggests that it is possible to kickstart the spinal cord to regenerate and reconnect even incases of severe trauma. Up until now it has only been the case that the central nervous systemcan regenerate after minor trauma and that severe injuries cannot be repaired by the body alone.

100% Recuperation after SCI

The application of this electrical and chemical stimulation of the spinal cord will be under

scrutiny in human clinical trials soon. Courtine hopes to start such spinal cord injury treatmenttrials in the next couple of years and his claims of 100% recuperation of voluntary movement

in the studys rats are sure to attract attention and funding for such work.

Stem Cell Skin Grafts and New Blood Vessels

Treatment Success Stories


This has been quite the week for innovation in regenerative medicine as a ten year old girl issaved by a cloned blood vessel and a three year old gets a skin graft made from her own stemcells. The techniques used in each procedure differ but without stem cell research there was littlelikelihood of either child surviving.

New Vein for Ten Year OldUsing Her Own Stem Cells

The ten year old in question is a Swedish girl with a condition affecting blood flow between herliver and the intestines, creating problems such as internal bleeding and severely affecting her

quality of life and chance of survival. In this patients case artificial grafts used to bypassextrahepatic portal vein obstruction had already failed, leaving physicians with few other optionsfor treatment. According to a study published in the Lancet, the girl has now been given a newblood vessel grown using her own stem cells to replace the faulty blood vessel and she is alreadyreported to have experienced a significant improvement in her quality of life.

Home-Grown Blood Vessel Replacements
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The blood vessel was grown using a donor vein from a dead man, which was then stripped of itsown cells and bathed in the girls stem cells to encourage growth into a new blood vessel. Thetechnology is similar to that which produced a working replacement trachea (windpipe) for apatient last year, also reported on stemcelltreatments.org. The benefit of such stem cell treatmentis that the replacement organ or blood vessel is essentially home-grown, leaving little risk of

tissue rejection, or need for immunosuppressants as a lifelong drug regime.

Decellularisation and Stem Cell Baths

The physicians involved in the procedure, which took place at the University of Gothenburg andShalgrenska University Hospital, used a process called decellularisation to wash the donors cells

from the scaffold of the blood vessel. This technique employs enzymes and detergents in anumber of cycles to break down and remove the dead persons cells. Using stem cells taken fromthe ten year olds bone marrow, the scientists then grew a new blood vessel able to be grafted

into place after the faulty blood vessel was removed. Such stem cell therapy allowed the patientto avoid undergoing surgery to harvest a deep vein from the neck or leg which could itself result

in permanent damage including lower limb disorders.

Other Stem Cell Successes

Although the stem cell surgery appears to have been a great success it is just one example of thistechnique and proper clinical trials would need conducting before the treatment becomes widelyavailable. The same goes for the treatment received by a severely burned three year old in South

Africa who remains in a coma but whose chances of survival have greatly improved after a rarestem cell skin graft.

Stem Cell Skin Grafts for Burns Victim

The toddler from Johannesburg suffered burns across 80% of her body in a gas explosion at afamily barbecue. She has spent months in hospital, where she battled pneumonia, kidney failure,and a number of heart attacks, as well as swelling to three times her usual size due to the extremeburns. Such patients rarely survive but the girl has now undergone experimental stem cellsurgery to give her a new layer of cloned skin.

Growing New Skin from Stem Cells

Taking stem cells from the tiny portion of the toddlers skin that survived the fire, a laboratory in

Boston was able to clone the skin using mouse cells as a scaffold. Genzyme Laboratory hasproduced such skin grafts before for use in Europe and the US but this is the first time that theyhave been used in Africa. The patient was finally able to be stabilized on Monday in order toundergo the stem cell skin graft for burns and so, on Monday evening, a courier arrived at the


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hospital in Johannesburg with a stainless steel container carrying thirty to forty new grafts ofskin for Isabelle Kruger.

Stem Cell Graft Girl in Induced Coma

The delicate layers of skin had to be grafted within twenty-four hours of leaving the laboratoryand, luckily, everything ran on time as a reconstructive plastic surgeon used staples andabsorbent stitches to attach the girls new skin to her face and other areas. The girl is currently inan induced coma but the hope is that the new skin grafts will help her to maintain blood pressure,resist infection, and regain strength as she heals. Isabella will spend a week wrapped inprotective dressings and foam and will be sedated in order to reduce the risk of the skin graftstearing or sliding off before grafting. It will be two weeks before the doctors will be able to tell ifthe skin grafts have successfully taken, but they remain optimistic given the three year oldsextraordinary survival so far.

Stem Cell Therapy Future

Unfortunately, these stories of experimental stem cell therapy successes remain newsworthy dueto their relative scarcity. Such patients can be considered lucky to have had access to innovativehospitals, persistence of family and medical staff, and the ability to raise funds to cover the costof such regenerative medicine procedures. The hope is that, with more success stories like these,the stem cell treatments will be properly investigated in clinical trials and approved for morewidespread use, thus lowering their cost.

Reference

Olausson, M., Patil, P.B., et al, Transplantation of an allogeneic vein bioengineered with

autologous stem cells: a proof-of-concept study, The Lancet, Early Online Publication, 14 June2012, doi:10.1016/S0140-6736(12)60633-3.

Dental Stem Cells Better Than Bone

Marrow-Derived Stem Cells, Researchers

Say.


In a recent issue of Cell Transplantation, two studies report on the use ofdental pulp stem cellpopulations and their potential uses in stem cell therapy. The researchers found that inducedpluripotent stem cells created from immature dental pulp stem cells may actually haveadvantages over other sources of stem cells due to longer telomeres and improved reversetranscriptase activity. Could your dentist be throwing away a vital piece of medical material aftera routine tooth-extraction? Is it time to reconsider saving a tooth to harvest stem cells?Induced Pluripotency in Dental Stem Cells
http://stemcelltreatments.org/http://stemcelltreatments.org/glossary/pluripotent/http://stemcelltreatments.org/glossary/stem-cells/http://stemcelltreatments.org/glossary/telomere/http://stemcelltreatments.org/glossary/telomere/http://stemcelltreatments.org/glossary/stem-cells/http://stemcelltreatments.org/glossary/pluripotent/http://stemcelltreatments.org/


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The stem cell scientists from Brazil and America looked at immature dental pulp stem cells(IDPSCs) as an alternative option to procure iPSCs. These kinds of cells are similar to embryonicstem cells in terms of their capacity to produce all other cell types, rather than being specificproducers of a single type of cell or a small number of cells. Finding easily available sources ofstem cells means that scientists have more opportunity to research certain genetic diseases and to

evaluate the effects of new pharmaceuticals without the dangers of human clinical trials.

Reprogramming Dental Stem Cells

In these studies the researchers managed to reprogramme human immature dental pulp stem cellswithin a short timeframe and with ease. However, they do note that the techniques to producesuch iPSCs do require refinement. The advantages of using human dental pulp stem cells includethe ability to do so without needing to use additional immunosuppressive techniques. Stem cellsfrom teeth and dental pulp could have applications such as helping with the repair of boneabnormalities or trauma, as well as aiding regeneration in tissues other than bone.

Stem Cells from Teeth Vs. Bone Marrow-Derived Stem Cells

Researchers in Korea have also been working on dental stem cells and have isolated a specificstem cell population of human dental papilla stem cells (DPaSCs). These stem cells producedentin and dental pulp, and have similar features to bone marrow-derived mesenchymal stemcells (MSCs). However, the dental pulp stem cells were found to actually have longer telomeres,more telomerase activity, and higher reverse transcriptase activity than MSCs. These are allfactors which determine the viability of stem cells and low levels of activity, or short telomeresin some MSCs affect the ability to expand stem cell populations in the laboratory. The DPaSCsare particularly suited for stem cell research and uses in regenerative medicine and are moreaccessible than the stem cells in bone marrow.

Next time youre having a tooth pulled ask your dentist if theyre signed up to a dental stem cell

saving program, who knows, that bloody mess could save your life one day.

References

Beltro-Braga, P. C. B.; Pignatari, G. C.; Maiorka, P. C.; Oliveira, N. A. J.; Lizier, N. F.;Wenceslau, C. V.; Miglino, M. A.; Muotri, A. R.; Kerkis, I. Feeder-free derivation of inducedpluripotent stem cells from human immature dental pulp stem cells. Cell Transplant. 20(11-12):1707-1719;2011.

Jeon, B. G.; Kang, E. J.; Mohana Kumar, B.; Maeng, G. H.; Ock, S. A.; Kwack, D. O.; Park, B.W.; Rho, G. J. Comparative Analysis of Telomere Length, Telomerase and ReverseTranscriptase Activity in Human Dental Stem Cells. Cell Transplant. 20(11-12):1693-1705;2011.

Source: Cell Transplantation Center of Excellence for Aging and Brain Repair


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Stem Cell Transplantation to Treat Leukemia

Cancer therapy (chemotherapy, radiation therapy, etc.) can damage or destroy normal cells, aswell as cancer cells. Many chemotherapeutic drugs, in particular, can harm rapidly dividing cells

such as the blood-forming stem cells of the bone marrow. Yet high drug doses are needed to treatleukemia effectively. So what can be done?

Physicians have begun to solve this problem by performing stem cell transplantation (SCT).Stem cells are blood-forming (hematopoietic) cells of the bone marrow; they continuously divideto form the new blood cells that populate the arteries and veins. The SCT procedure enablesphysicians to give chemotherapy and radiotherapy in doses that are strong enough to eliminateleukemia cells. The injured bone marrow then is replenished by a transplant of stem cells, whichcan manufacture the necessary new blood cells.

Stem cells for SCT can be gathered from different sources:

aspiration (suctioning) directly from the bone marrow at the back of the hip crest;

leukapheresis (also known as apheresis), separation of white blood cells in blood from thebloodstream; or

umbilical cord cells (stem cells obtained from umbilical cord blood), usually from donationsmade by healthy siblings who are born after a child who has leukemia.

The cells are carefully frozen and stored until the patient has completed high-dose treatments forleukemia. Such treatments usually consist of a 3-day course of chemotherapy (for example, with

cyclophosphamide, cytarabine, etoposide, melphalan, or busulfan) with/without a 3-day courseof total body irradiation (TBI). After therapy, the stem cells are thawed and given to the patientby means of a blood transfusion.

SCT are classified as autologous or allogeneic, based on characteristics of the cell donor.Autologous SCT, also known as autologous bone marrow transplant (autoBMT), is a procedurein which a patient's own stem cells (immature cells from which all blood cells develop) areremoved from the bone marrow. This type of transplant is not frequently used, because it is verydifficult to guarantee that normal stem cells have been separated from leukemic cells, even afterpurging, that is treatment of stem cells with drugs, immunologic agents, heat, or othersubstances/methods to kill or remove leukemic cells.

Another form of autologous SCT is peripheral blood stem cell transplantation, or leukapheresis.The patient's blood is passed through a machine that removes the stem cells, then returns theblood to the patient. This procedure usually takes 3 or 4 hours to complete. The stem cells mayor may not be treated with drugs to kill any remaining leukemia cells. The stem cells are stored


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until they are transplanted back into the patient. Leukapheresis may be performed alone or withautoBMT, although most physicians prefer to use leukapheresis by itself.

Allogeneic SCT, also known as allogeneic bone marrow transplant (alloBMT), is a form oftransplant in which the stem cells are gathered from a donor whose tissue type closely matches

the patient's tissue type. Such donors usually are relatives (brother, sister, child) or, occasionally,a matched unrelated donor (MUD). AlloBMT usually is reserved for individuals who areyounger than 55 and who have a compatible family donor - that is, a donor with compatiblehuman leukocyte antigen (HLA), a protein found on the surface of some cells, such asleukocytes). Allogeneic donor cells actually may help to fight leukemia cells because theyinitiate a response known as the "graft versus leukemia" reaction.

If the person receives an allogeneic transplant, he or she must be treated with drugs that suppressrejection reactions (e.g., cyclosporine, methotrexate, prednisone, and antilymphocyte globulin[ALG] or antithymocyte globulin [ATG]). For example, "graft-versus-host disease" (GVHD) is aresult of rejection reactions that occur in 25 to 50% of cases. The leukemia patient should ensure

that SCT is performed at a qualified medical facility. The treatment staff should be experiencedin all types of transplants, including MUD transplants, as well as patient care during the recoveryperiod.

Transplant patients typically are kept in protective isolation in the hospital until their total whiteblood cell (WBC) count is above 500. During this time, the individual receives supportive care,such as intravenous nutrition, treatment with antibacterial and antifungal medications, andtransfusions with red blood cells and platelets. Within 2 to 3 weeks, the stem cells usually beginto make white blood cells. Next, platelets are produced, followed several weeks later by themanufacture of red blood cells. Once the WBC count approaches 1000, the patient generally canbe discharged from the hospital. Daily outpatient check-ups may be scheduled for several weeks,

followed by regular appointments over a 6-month period. The individual's oncologist usually willschedule an exam at the SCT clinic 1 year after treatment; thereafter, clinic appointments aremade only if symptoms return.

Side effects due to SCT may occur shortly after treatment, or they may develop much later. Earlycomplications usually are related to the cellular injury caused by high-dose chemotherapy andradiotherapy (for example, temporary hair loss, anemia, leukopenia, thrombocytopenia, andgastrointestinal symptoms like nausea, vomiting, and diarrhea. Long-term or chroniccomplications may include:

Chronic graft-versus-host diseaseor GVHD that occurs after 100 days. This autoimmunedisorder develops when donor stem cells make immune cells that attack tissues of the patient'sskin, gut, mouth, genitalia, and other organs. Typical features include dry mouth and eyes; skinchanges such as thickening, hair loss, dryness, and rashes; fatigue; muscle pain and weakness;and infection.


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Irreversible sterility in men and women who have received total body irradiation (TBI) or high-dose busulfan chemotherapy. Women will experience radiation-induced menopause and willrequire gynecological observation after the first 100 days. Hormone replacement therapy (HRT)will be needed in pre-menopausal women.

Endocrine (hormonal) system malfunction, particularly of the thyroid gland. Hypothyroidism(low thyroid activity) is frequent, so regular thyroid screening is needed after SC.

Bone marrow toxicity (poisonous damage), especially when manifested as asceptic necrosis -bone cell death without infection. Severe bone and/or joint damage may require surgicalreplacement.

Respiratory symptoms and impairment (e.g., shortness of breath) due to radiation-related lungdamage.

Cataract, an abnormality of the lens of the eye which blocks light and impairs vision.

Thrombotic microangiopathy (TM), clot formation in the small blood vessels), a condition thatincludes hemolytic uremic syndrome (HUS; bloody urine) and thrombocytopenic purpura (TTP;purplish discoloration of the skin caused by internal hemorrhaging related to a low plateletcount). TM has multiple causes and, unfortunately, often does not respond well to therapy.

Documents

Stem Cell Therapy2