question: Why isn't the regrowth of nerves and other key cells using stem cells not more popular or more researched if it works so well?
comment: The ethics of Stem Cells are a little fuzzy. The best Stem Cells for use in Humans come from Human Fetuses. That means harvesting cells from freshly dead babies. Any situation that leads to a researcher extracting fresh stem cells is going to stumble afoul some dark decisions by one party or the other.
passages: Keilhoff et al. (2006) performed a study comparing the nerve regeneration capacity of non-differentiated and transdifferentiated MSCs to Schwann cells in devitalized muscle grafts bridging a 2-cm gap in the rat sciatic nerve. All cells were autologous. The transdifferentiated MSCs were cultured in a mixture of factors in order to promote Schwann cell-like cell formation. The undifferentiated MSCs demonstrated no regenerative capacity, while the transdifferentiated MSCs showed some regenerative capacity, though it did not reach the capacity of the Schwann cells.
  
  Section::::Cellular therapies.:Stem cells.:Ectomesenchymal stem cells (EMSCs).
   Treatments are also in clinical trials to repair and regenerate peripheral nerves. Peripheral nerves are more likely to be damaged, but the effects of the damage are not as widespread as seen in injuries to the spinal cord. Treatments are currently in clinical trials to repair severed nerves, with early success. Stem cells induced to a neural fate injected in to a severed nerve. Within four weeks, regeneration of previously damaged stem cells and completely formed nerve bundles were observed.
   Stem cell transplantation is an important avenue for SCI research: the goal is to replace lost spinal cord cells, allow reconnection in broken neural circuits by regrowing axons, and to create an environment in the tissues that is favorable to growth. A key avenue of SCI research is research on stem cells, which can differentiate into other types of cells—including those lost after SCI. Types of cells being researched for use in SCI include embryonic stem cells, neural stem cells, mesenchymal stem cells, olfactory ensheathing cells, Schwann cells, activated macrophages, and induced pluripotent stem cells. Hundreds of stem cell studies have been done in humans, with promising but inconclusive results. An ongoing Phase 2 trial in 2016 presented data showing that after 90 days, 2 out of 4 subjects had already improved two motor levels and had thus already achieved its endpoint of 2/5 patients improving two levels within 6–12 months. Six-month data is expected in January 2017.
   It has been shown that bone marrow-derived cells could be the source of progenitor cells of multiple cell lineages, and a 2004 study suggested that one of these cell types was involved in lung regeneration. Therefore, a potential source of cells for lung regeneration has been found; however, due to advances in inducing stem cells and directing their differentiation, major progress in lung regeneration has consistently featured the use of patient-derived iPSCs and bioscaffolds.
   In 2010, Geron Corporation began the world's first clinical trial of human embryonic stem cell treatment for spinal cord injuries, based on the research of Keirstead's team at UC Irvine. However, the trials ended after a year due to lack of funds.
   Alternatively, these stem cells can act as carriers for other therapies, though the positive effects of using stem cells as a delivery mechanism has not been confirmed. Direct stem cell delivery has an increased beneficial effect if they are directed to be neuronal cells "in vitro". This way, the risks associated with undirected stem cells are decreased; additionally, injuries that do not have a specific boundary could be treated efficiently.
  
  Section::::CNS.:Current treatments and research.:Delivery of molecules to the injury site.
   In another study done in 2011 used stem cells to treat cerebral palsy. This study, however, was not as successful as the Parkinson's treatment. In this case stem cells were used to treat animal models who had been injured in a way that mimicked CP. This brings up a neuroethical issue of animal models used in science. Since most of their "diseases" are inflicted and do not occur naturally, they can not always be reliable examples of how a person with the actual disease would respond to treatment. The stem cells used did survive implantation, but did not show significant nerve regeneration. However, studies are ongoing in this area.
   Until recently, the use of cultured mesenchymal stem cells to regenerate cartilage has been primarily in research with animal models. There are now, however, two published case reports of the above technique being used to successfully regenerate articular and meniscus cartilage in human knees. This technique has yet to be shown effective in a study involving a larger group of patients, however the same team of researchers have published a large safety study (n=227) showing fewer complications than would normally be associated with surgical procedures.
   Japanese researchers in 2006 discovered that adding certain transcription factors to cells caused them to be able to differentiate again. This way a patient's own tissues could be used, reducing the chance of transplant rejection.
  
  Section::::Engineering approaches.
  
  Recent approaches have used various engineering techniques to improve spinal cord injury repair. 
   Because of their combined abilities of unlimited expansion and pluripotency, embryonic stem cells remain a theoretically potential source for regenerative medicine and tissue replacement after injury or disease., however, there are currently no approved treatments using ES cells. The first human trial was approved by the US Food and Drug Administration in January 2009. However, the human trial was not initiated until October 13, 2010 in Atlanta for spinal cord injury research. On November 14, 2011 the company conducting the trial (Geron Corporation) announced that it will discontinue further development of its stem cell programs. 
   Stem cell technologies are always salient both in the minds of the general public and scientists because of their large potential. Recent advances in stem cell research have allowed researchers to ethically pursue studies in nearly every facet of the body, which includes the brain. Research has shown that while most of the brain does not regenerate and is typically a very difficult environment to foster regeneration, there are portions of the brain with regenerative capabilities (specifically the hippocampus and the olfactory bulbs). Much of the research in central nervous system regeneration is how to overcome this poor regenerative quality of the brain. It is important to note that there are therapies that improve cognition and increase the amount of neural pathways, but this does not mean that there is a proliferation of neural cells in the brain. Rather, it is called a plastic rewiring of the brain ("plastic" because it indicates malleability) and is considered a vital part of growth. Nevertheless, many problems in patients stem from death of neurons in the brain, and researchers in the field are striving to produce technologies that enable regeneration in patients with stroke, Parkinson's diseases, severe trauma, and Alzheimer's disease, as well as many others. While still in fledgling stages of development, researchers have recently begun making very interesting progress in attempting to treat these diseases. Researchers have recently successfully produced dopaminergic neurons for transplant in patients with Parkinson's diseases with the hopes that they will be able to move again with a more steady supply of dopamine. Many researchers are building scaffolds that could be transplanted into a patient with spinal cord trauma to present an environment that promotes growth of axons (portions of the cell attributed with transmission of electrical signals) so that patients unable to move or feel might be able to do so again. The potentials are wide-ranging, but it is important to note that many of these therapies are still in the laboratory phase and are slowly being adapted in the clinic. Some scientists remain skeptical with the development of the field, and warn that there is a much larger chance that electrical prosthesis will be developed to solve clinical problems such as hearing loss or paralysis before cell therapy is used in a clinic.
   Section::::Research and applications.:Neural tissue regeneration.:Engineering strategies for repair.
  
  Engineering strategies for the repair of spinal cord injury are focused on creating a friendly environment for nerve regeneration. Only PNS nerve damage has been clinically possible so far, but advances in research of genetic techniques and biomaterials demonstrate the potential for SC nerves to regenerate in permissible environments.
  
  Section::::Research and applications.:Neural tissue regeneration.:Engineering strategies for repair.:Grafts.
   For years, the concept of harvesting stem cells and re-implanting them into one's own body to regenerate organs and tissues has been embraced and researched in animal models. In particular, mesenchymal stem cells have been shown in animal models to regenerate cartilage[1]. Recently, there has been a published case report of decrease in knee pain in a single individual using autologous mesenchymal stem cells.[2]An advantage to this approach is that a person's own stem cells are used, avoiding transmission of genetic diseases. It is also minimally invasive, minimally painful and has a very short recovery period. This alternative to the current available treatments was shown not to cause cancer in patients who were followed for 3 years after the procedure.
   BULLET::::- An important area for future studies in the iPSC field is directly testing iPSC tumorigenicity using methods that mimic the approaches that would be used for regenerative medicine therapies. Such studies are crucial since iPSCs not only form teratoma, but also mice derived from iPSCs have a high incidence of death from malignant cancer. A 2010 paper was published in the journal Stem Cells indicating that iPS cells are far more tumorigenic than ESC, supporting the notion that iPS cell safety is a serious concern.
   A different trial is underway for a patch made of a porous substance onto which the stem cells are "seeded" in order to induce tissue regeneration in heart defects. Tissue was regenerated and the patch was well incorporated into the heart tissue. This is thought to be due, in part, to improved angiogenesis and reduction of inflammation. Although cardiomyocytes were produced from the mesenchymal stem cells, they did not appear to be contractile. Other treatments that induced a cardiac fate in the cells before transplanting had greater success at creating contractile heart tissue.
  
  Section::::Veterinary medicine.:Muscle repairs.:Nervous system repairs.
   The use of stem cells for treatment has become a growing interest in the scientific community. Distinguishing between an ESC and its intermediate progenitor is nearly impossible, so research is now being done broadly on EPCs. One study showed that brief exposure to sevoflurane promoted growth and proliferation of EPCs. Sevoflurane is used in general anesthesia, but this finding shows the potential to induce endothelial progenitors. Using stem cells for cell replacement therapies is known as "regenerative medicine", which is a booming field that is now working on transplanting cells as opposed to bigger tissues or organs.
  
  Section::::Clinical significance.
   visual-guided behaviors of experimental animals for 6 weeks after transplantation. However, clinical trials have been successful: ten patients suffering from retinitis pigmentosa have had their eyesight restored – including a woman who had only 17 percent of her vision left.
  
  Section::::Rejuvenation to iPSCs.:Differentiated cell types.:Lung and airway epithelial cells.
  
  Chronic lung diseases such as idiopathic pulmonary fibrosis and cystic fibrosis or chronic obstructive pulmonary disease and asthma are leading causes of morbidity and mortality worldwide with a considerable human, societal and financial burden. So there is an urgent need for effective cell therapy and lung tissue engineering.
   Stem cell transplantation has been identified as another possible therapy for axonal regeneration in the central nervous system by delivering these cells directly to the site of the spinal cord injury. Both OEG and neural stem/progenitor cells (NSPCs) have been successfully transplanted in the central nervous system of adult rats and have had either positive or neutral results as a method of neurogenesis and axonal regeneration; however, neither method has been shown to have long term beneficial effects, as cell survival is usually less than 1% after transplantation. The inability of these cells to sustain after transplantation is a result of inflammation, the inability of a sufficient matrix to thrive and create a uniform population of cells, or the migratory response of the cells needed to fully repair the site of the injury. Another current issue with the survival of the cells is utilizing the proper biomaterials to deliver them to the site of the injury.
   Because there are so many factors that contribute to the success or failure of neural tissue engineering, there are many difficulties that arise in using neural tissue engineering to treat CNS and PNS injuries. First, the therapy needs to be delivered to the site of the injury. This means that the injury site needs to be accessed by surgery or drug delivery. Both of these methods have inherent risks and difficulties in themselves, compounding the problems associated with the treatments. A second concern is keeping the therapy at the site of the injury. Stem cells have a tendency to migrate out of the injury site to other sections of the brain, thus the therapy is not as effective as it could be as when the cells stay at the injury site. Additionally, the delivery of stem cells and other morphogens to the site of injury can cause more harm than good if they induce tumorigenesis, inflammation, or other unforeseen effects. Finally, the findings in laboratories may not translate to practical clinical treatments. Treatments are successful in a lab, or even an animal model of the injury, may not be effective in a human patient.
   One of the most significant barriers to the procedure is the inability of nerve tissue to heal properly; scarred nerve tissue does not transmit signals well (this is why a spinal cord injury is so devastating). Research at the Wistar Institute of the University of Pennsylvania involving tissue-regenerating mice (known as MRL mice) may provide pointers for further research as to how to regenerate nerves without scarring. It is possible that a completely clean cut will not generate scarred tissue.
   The need for neural tissue engineering arises from the difficulty of the nerve cells and neural tissues to regenerate on their own after neural damage has occurred. The PNS has some, but limited, regeneration of neural cells. Adult stem cell neurogenesis in the CNS has been found to occur in the hippocampus, the subventricular zone (SVZ), and spinal cord. CNS injuries can be caused by stroke, neurodegenerative disorders, trauma, or encephalopathy. A few methods currently being investigated to treat CNS injuries are: implanting stem cells directly into the injury site, delivering morphogens to the injury site, or growing neural tissue "in vitro" with neural stem or progenitor cells in a 3D scaffold. Proposed use of electrospun polymeric fibrous scaffolds for neural repair substrates dates back to at least 1986 in a NIH SBIR application from Simon. For the PNS, a severed nerve can be reconnected and reinnervated using grafts or guidance of the existing nerve through a channel.
   Neural stem cells (NSCs) are multipotent; they can differentiate into different kinds of neural cells, either neurons or glia, namely oligodendrocytes and astrocytes. The hope is that these cells when injected into an injured spinal cord will replace killed neurons and oligodendrocytes and secrete factors that support growth. However they may fail to differentiate into neurons when transplanted, either remaining undifferentiated or becoming glia. A phase I/II clinical trials implanting NSCs into humans with SCI began in 2011 and ended in June 2015.
  
  Section::::Stem cells.:Mesenchymal stem cells.
   On January 23, 2009, Phase I clinical trials for transplantation of oligodendrocytes (a cell type of the brain and spinal cord) derived from human ES cells into spinal cord-injured individuals received approval from the U.S. Food and Drug Administration (FDA), marking it the world's first human ES cell human trial. The study leading to this scientific advancement was conducted by Hans Keirstead and colleagues at the University of California, Irvine and supported by Geron Corporation of Menlo Park, CA, founded by Michael D. West, PhD. A previous experiment had shown an improvement in locomotor recovery in spinal cord-injured rats after a 7-day delayed transplantation of human ES cells that had been pushed into an oligodendrocytic lineage. The phase I clinical study was designed to enroll about eight to ten paraplegics who have had their injuries no longer than two weeks before the trial begins, since the cells must be injected before scar tissue is able to form. The researchers emphasized that the injections were not expected to fully cure the patients and restore all mobility. Based on the results of the rodent trials, researchers speculated that restoration of myelin sheathes and an increase in mobility might occur. This first trial was primarily designed to test the safety of these procedures and if everything went well, it was hoped that it would lead to future studies that involve people with more severe disabilities. The trial was put on hold in August 2009 due to FDA concerns regarding a small number of microscopic cysts found in several treated rat models but the hold was lifted on July 30, 2010.
   Regarding neuroprotective and regenerative treatments such as stem cell therapy, while their research is considered of high importance at the moment they are only a promise of future therapeutic approaches. Likewise, there are not any effective treatments for the progressive variants of the disease. Many of the newest drugs as well as those under development are probably going to be evaluated as therapies for PPMS or SPMS, and their improved effectiveness when compared with previously existing drugs may eventually lead to a positive result in these groups of patients.
  
  Section::::Research directions.:Etiology and pathogenesis.
   Mesenchymal stem cells do not need to come from fetuses, so avoid difficulties around ethics; they come from tissues including bone marrow, adipose tissue, the umbilical cord. They are thought to be pluripotent. Unlike other types of stem cells, mesenchymal cells do not present the threat of tumor formation or triggering an immune system response. Animal studies with injection of bone marrow stem cells have shown improvement in motor function; however not so in a human trial a year post-injury. More trials are underway. Adipose and umbilical tissue stem cells need further study before human trials can be performed, but two Korean studies were begun to investigate adipose cells in SCI patients.
  
raw_presuppositions: Stem cell research is complete and detailed. If something works well, it should be popular or more researched.
raw_corrections: The ethics of stem cell research is still developing. Even if something works well, it may not be popular or more researched if the ethics are fuzzy.