Stem cell therapy is the use of stem cells to treat or prevent disease or conditions.
Bone marrow transplantation is the most widely used stem cell therapy, but some therapies derived from cord blood are also used. Research is underway to develop various sources for stem cells, as well as to apply stem cell treatments for neurodegenerative diseases and conditions such as diabetes and heart disease, among others.
Stem cell therapy has become controversial after such developments as the ability of scientists to isolate and cultivate embryonic stem cells, to create stem cells using somatic cell nuclear transfer and use their techniques to create pluripotent stem cells. This controversy is often associated with the politics of abortion and human cloning. In addition, efforts to market treatments based on cord blood transplants that are stored have become controversial.
Video Stem-cell therapy
Medical use
For more than 30 years, bone marrow has been used to treat cancer patients with conditions such as leukemia and lymphoma; this is the only form of stem cell therapy that is widely practiced. During chemotherapy, most of the developing cells are killed by cytotoxic agents. These agents, however, can not distinguish between leukemia or neoplastic cells, and hematopoietic stem cells in the bone marrow. This is a side effect of conventional chemotherapy strategies that are deprived by stem cell transplantation; the healthy bone marrow donor reintroduces functional stem cells to replace the lost cells in the host's body during treatment. Transplanted cells also produce an immune response that helps to kill cancer cells; this process can go too far, however, cause graft vs. host disease, the most serious side effect of this treatment.
Another stem cell therapy called Prochymal, approved conditionally in Canada in 2012 for the management of acute graft-vs-lute disease in children who are not steroid-responsive. It is an allogenic stem therapy based on mesenchymal stem cells (MSCs) derived from adult donor bone marrow. MSC is purified from marrow, cultured and packed, with up to 10,000 doses originating from a single donor. Doses are kept frozen until needed.
The FDA has approved five hematopoietic stem cell products derived from cord blood, for the treatment of blood and immunologic diseases.
In 2014, the European Medicines Agency recommends approval of limbal stem cells for people with severe deficiency of limbal stem cells because of burns in the eyes.
Maps Stem-cell therapy
Research
Stem cells are being studied for a number of reasons. Molecules and exosomes released from stem cells are also being studied in an attempt to make the drug. The paracrine-soluble factor produced by stem cells, known as stem cell secretions, has been found to be the primary mechanism by which stem cell-based therapies mediate their effects on degenerative, auto-immune and inflammatory diseases.
Apps
Neurodegeneration
Research has been done on the effects of stem cells on animal models of brain degeneration, such as in Parkinson's, Amyotrophic lateral sclerosis, and Alzheimer's disease. There are early studies related to multiple sclerosis.
A healthy adult brain contains neural stem cells that divide to maintain the number of common stem cells, or become a progenitor cell. In healthy adult laboratory animals, progenitor cells migrate within the brain and serve primarily to keep the olfactory neuron population (the sense of smell). Pharmacologic activation of endogenous neural stem cells has been reported to induce neuroprotection and behavioral recovery in mice models of neurologic disorders.
Brain injury and spinal cord injury
Stroke and traumatic brain injury cause cell death, characterized by loss of neurons and oligodendrocytes in the brain. Clinical and animal studies have been carried into the use of stem cells in cases of spinal injuries.
Heart
Stem cells are studied in people with severe heart disease. Bodo-Eckehard Strauer's work was discredited by identifying hundreds of factual contradictions. Among several clinical trials reporting that adult stem cell therapy is safe and effective, concrete evidence of benefits has been reported only from several studies. Some early clinical trials achieved only modest improvement in cardiac function after the use of bone marrow stem cell therapy.
Stem cell therapy for the treatment of myocardial infarction usually uses autologous marrow stem cells, but other types of adult stem cells may be used, such as adipose-derived stem cells.
Possible recovery mechanisms include:
- Heart muscle cell generation
- Stimulates the growth of new blood vessels to repopulate damaged heart tissue
- Growth factor secretion
Criticism
In 2013, autologous bone marrow stem cell research on ventricular function was found to contain "hundreds" of nonconformities. Critics reported that out of 48 reports there appeared to be only five underlying tests, and that in many cases whether they were random or just observer-versus-rejection-observation, conflicted between reports from the same experiment. A pair of identical basic characteristic reports and outcomes, presented in two publications as, respectively, 578 randomized trial patients and as an observational study of 391 patients. Another report required (not possible) negative deviation standard on a subset of patients, or containing fractional patients, negative NYHA classes. Overall more patients were published because they had received stem cells in trials, rather than the number of stem cells that were processed in the hospital laboratory during that time. The university investigation, closed in 2012 without reporting, reopened in July 2013.
In 2014, a meta-analysis on stem cell therapy using bone marrow stem cells for heart disease revealed differences in published clinical trial reports, where studies with a higher number of nonconformities showed an increase in effect size. Other meta-analyzes based on intra-subject data from 12 randomized trials were unable to find significant benefits of stem cell therapy at primary endpoints, such as major side effects or an increase in the size of cardiac function, concluding there was no benefit.
The TIME trial, which used a randomized, double blind, placebo-controlled trial, concluded that "administration of bone marrow mononuclear cells did not improve the recovery of LV function for 2 years" in people with myocardial infarction. Thus, a BOOST-2 trial conducted at 10 medical centers in Germany and Norway reported that the trial results "do not support the use of nuclear BMCs in patients with STEMI and simply reduce LVEF". In addition, trials also did not meet other secondary MRI endpoints, leading to the conclusion that intracoronary bone marrow stem therapy does not offer any functional or clinical benefit.
Blood cell formation
The specificity of the human immune cell repertoire is what allows the human body to defend itself from fast adapting antigens. However, the immune system is susceptible to degradation in the pathogenesis of the disease, and because of the important role it plays in overall defense, its degradation is often fatal to the organism as a whole. Hematopoietic cell disease is diagnosed and classified by a subspecialty of pathology known as hematopathology. The specificity of immune cells is that it allows the recognition of foreign antigens, leading to further challenges in the treatment of immune diseases. An identical match between the donor and the recipient should be done for successful transplant treatment, but the matches are rare, even between first-tier brothers. Research using both hematopoietic adult stem cells and embryonic stem cells has provided insight into the possible mechanisms and methods of treatment for many of these diseases.
Completely mature human red blood cells can be produced by ex vivo by hematopoietic stem cells (HSC), which are the precursors of red blood cells. In this process, HSC grows together with stromal cells, creating an environment that mimics the condition of the bone marrow, the natural site of red blood cell growth. Erythropoietin, a growth factor, is added, inducing stem cells to settle terminal differentiation into red blood cells. Further research into this technique should have potential benefits for gene therapy, blood transfusion, and topical medications.
Back rolls
In 2004, scientists at King's College London found a way to grow complete teeth in mice and able to grow biotechnology teeth that stand alone in the laboratory. The researchers believe that dental regeneration technology can be used to grow live tooth in human patients.
Theoretically, stem cells taken from the patient can be coaxed in the laboratory transformed into tooth buds which, when planted in the gums, will give rise to new teeth, and are expected to grow within more than three weeks. It will merge with the jawbone and release the chemicals that push the nerves and blood vessels to connect with it. The process is similar to what happens when humans grow their original adult teeth. Many challenges remain, however, before stem cells can be an option for lost tooth replacement in the future.
The growth of cochlear hair cells
Heller has reported success in regrowing the hair cells of the cochlea with the use of embryonic stem cells.
Blindness and visual impairment
Since 2003, researchers have successfully transplanted corneal stem cells into damaged eyes to restore vision. "The retinal cell sheets used by the team are taken from aborted fetuses, which some people find unpleasant." When these sheets are transplanted over the damaged cornea, the stem cells stimulate the renewed improvement, finally restoring the vision. The latest developments were in June 2005, when researchers at Queen Victoria Hospital in Sussex, England were able to restore the views of forty patients using the same technique. The group, led by Sheraz Daya, managed to use adult stem cells obtained from patients, relatives, or even corpses. Further tests are in progress.
Pancreatic beta cells
Diabetic patients lose the function of insulin-producing beta cells in the pancreas. In recent experiments, scientists have been able to persuade embryonic stem cells to transform into beta cells in the laboratory. In theory if the beta cells are successfully transplanted, they will be able to replace the damaged in diabetic patients.
Orthopedics
Clinical case reports in orthopedic treatment have been reported. To date, the focus in the literature for musculoskeletal treatment appears to be in mesenchymal stem cells. Centeno et al. has published evidence of increased MRI cartilage and meniscus volume in individual human subjects. Trial results that include a large number of subjects, have not been published. However, a published safety study conducted on a group of 227 patients over a 3-4 year period demonstrates adequate safety and minimal complications associated with mesenchymal cell transplantation.
Wakitani has also published a series of small cases of nine defects in five knees involving a transplant of mesenchymal stem surgery with coverage of chondral defects treated.
Wound healing
Stem cells can also be used to stimulate the growth of human tissue. In adults, the injured tissue is most often replaced by scar tissue, which is marked on the skin by irregular collagen structures, loss of hair follicles and irregular vascular structures. In the case of injured fetal tissue, however, injured tissue is replaced by normal tissue via stem cell activity. A possible method for tissue regeneration in adults is to place the "seed" of adult stem cells in the tissue "layer" in the wound bed and allow the stem cells to stimulate differentiation in the tissue bed cells. This method generates a regenerative response that is more similar to wound healing than the formation of adult scar tissue. Researchers are still investigating different aspects of the soil tissue conducive to regeneration.
Infertility
Human embryonic stem cell cultures in ovarian inactivated ovarian ovarian fibroblasts (POF) cause differentiation into germ cells (oocyte precursor cells and spermatozoa), as evidenced by gene expression analysis.
Human embryonic stem cells have been stimulated to form cells like Spermatozoon, but are still slightly damaged or defective. It has the potential to treat azoospermia.
In 2012, oogonial stem cells were isolated from adult rats and human ovaries and proved capable of forming mature oocytes. These cells have the potential to treat infertility.
HIV/AIDS
The destruction of the immune system by HIV is driven by the loss of CD4 T cells in peripheral blood and lymphoid tissue. Virus entry into CD4 cells is mediated by interactions with cellular chemokine receptors, most commonly CCR5 and CXCR4. Because subsequent viral replication requires the process of cellular gene expression, activated CD4 T cells are the primary target of productive HIV infection. Recently scientists have investigated alternative approaches to treat HIV-1/AIDS, based on the creation of disease-resistant immune systems through hematopoietic cell transplantation and autologous, gene-modified (progenitor) genes (GM) HSPC).
Clinical test
Regenerative care model
Stem cells allegedly mediate improvements through five main mechanisms: 1) provide anti-inflammatory effects; 2) adhere to damaged tissue and recruit other cells, such as endothelial progenitor cells, necessary for tissue growth; 3) support tissue remodeling more than former formation wound, 4) inhibits apoptosis, and 5) differentiates to bone, cartilage, tendon, and ligamentous tissue.
To further enrich the blood supply to the damaged areas, and consequently increase tissue regeneration, platelet-rich plasma can be used in conjunction with stem cell transplantation. The efficacy of some stem cell populations may also be affected by labor methods; for example, to regenerate bones, stem cells are often introduced in scaffolds where they produce minerals needed for functional bone formation.
Stem cells have also been shown to have low immunogenicity due to the relatively low number of MHC molecules found on the surface. In addition, they have been found to secrete chemokines that alter the immune response and increase new tissue tolerance. This allows allogenic treatments to be carried out without the risk of high rejection.
Drug discovery and biomedical research
The ability to grow an infinitely functional adult network in cultures through Directed Distederation creates new opportunities for drug research. Researchers can grow different cell lines and then test new drugs on each cell type to check for the possibility of in vitro interaction before doing the study in vivo. This is particularly important in drug development for use in veterinary research because of the possibility of species-specific interactions. The hope is that having these cell lines available for research use will reduce the need for animal research used because the effects on human tissue in vitro will provide insights that are not usually known before the animal testing phase.
- With the advent of induced pluripotent stem cells (iPSC), treatments are being explored and made for use in endangered low-end animals. Rather than need to harvest embryos or eggs, which is limited, researchers can remove mesenchymal stem cells more easily and greatly reduce the dangers in animals because of non-invasive techniques. This allows limited eggs to be used only for reproductive purposes.
Preservation
Stem cells are being explored for use in conservation efforts. Sperm stem cells have been taken from mice and placed into host mice and mature sperm are produced with the ability to produce proper offspring. There is currently research to find suitable hosts for the introduction of donor spermatogonium stem cells. If this is a viable option for conservationists, sperm can be produced from individuals with high genetic qualities who die before reaching sexual maturity, maintaining the line that should be lost.
Source for stem cells
Most stem cells devoted to regenerative therapy are generally isolated either from the patient's bone marrow or from adipose tissue. Mesenchymal stem cells can differentiate into bone-forming cells, cartilage, tendons, and ligaments, as well as other muscle, nerve and progenitor tissue, they have become the main type of stem cells studied in the treatment of diseases affecting this tissue. The number of stem cells transplanted into the damaged tissue can change the success of the treatment. Thus, stem cells derived from bone marrow aspiration, for example, are cultured in specialized laboratories for expansion into millions of cells. Although adipose-derived tissue also requires processing prior to use, the culture methodology for stem cells derived from adipose is not as large as that for cells derived from bone marrow. Although it is thought that stem cells derived from bone marrow are preferred for bone repair, cartilage, ligaments, and tendons, others believe that less challenging collection techniques and multi-cellular micro environments already exist in stem cell fractions derived from adipose making last. source of choice for autologous transplantation.
New sources of mesenchymal stem cells are being studied, including skin and dermis stem cells that are attractive because of the ease with which they can be harvested with minimal risk to animals. Hematopoetic stem cells have also been found to travel in the bloodstream and have the same distinguishing ability as other mesenchymal stem cells, again with a very non-invasive harvesting technique.
- There is a renewed interest in the use of extra-embryo mesenchymal stem cells. Research is underway to test the ability to distinguish stem cells found on the umbilical cord, egg yolk sac and placenta from different animals. These stem cells are considered to have more distinguishing capabilities than their adult counterparts, including the ability to more easily form endodermal tissues and ectodermal origin.
Embryonic stem cell lines
There is widespread controversy about the use of human embryonic stem cells. This controversy primarily targets techniques used to obtain new embryonic stem cell lines, which often require the destruction of blastocysts. The opposition to the use of human embryonic stem cells in research is often based on philosophical, moral, or religious objections. There are other stem cell studies that do not involve the destruction of human embryos, and such studies involve adult stem cells, amniotic stem cells, and pluripotent stem cells.
On January 23, 2009, the US Food and Drug Administration authorized Geron Corporation to begin the first clinical trial of embryonic stem cell based therapy in humans. The experiment aims to evaluate the drug GRNOPC1, the oligodendrocyte progenitor cells derived from embryonic cells, in patients with acute spinal cord injury. Trials were suspended in November 2011 so the company could focus on therapy in "the current environment of capital scarcity and uncertain economic conditions". In 2013 biotechnology and regenerative drug company BioTime (AMEX: BTX) acquired Geron's stem cell assets in stock transactions, with the aim of restarting clinical trials.
Mesenchymal stroma cells (MSC)
Scientists have reported that MSC when transfused immediately within hours of post-thawing may indicate diminished function or show decreased efficacy in treating diseases compared to MSCs in the log phase of cell growth (fresh), so cryopreservation MSC should be brought back to log growth phase cells in prior invitro cultures are given for clinical trials or experimental therapy, the MSC recycling will help recover from cell-acquired shock during freezing and thawing. Various clinical trials on failed MSCs that use cryopreserved products soon post when compared to clinical trials using fresh MSC.
Veterinary
Studies conducted on horses, dogs and cats can benefit the development of stem cell treatments in veterinary medicine and can target a wide range of injuries and illnesses such as myocardial infarction, stroke, tendon and ligamentous damage, osteoarthritis, osteochondrosis and muscular dystrophy. both in large animals, as well as humans. While cell-based therapeutic inquiry generally reflects human medical needs, the high frequency and severity of certain injuries on racehorses has placed veterinary medicine at the forefront of this new regenerative approach. Animal companion can serve as a clinically relevant model that is very similar to human disease.
Stem cell source
The veterinary application of stem cell therapy as a means of tissue regeneration has largely been shaped by studies beginning with the use of adult-derived mesenchymal stem cells to treat animals with injuries or defects affecting bone, cartilage, ligaments and/or tendons. There are two main categories of stem cells used for treatment: allogenic stem cells originating from genetically different donors in the same species and autologous mesenchymal stem cells, are from patients before use in various treatments. The third category, xenogenic stem cells, or stem cells originating from different species, is used primarily for research purposes, especially for human care.
Hard network repair
Bones have a unique and well-documented natural healing process that is usually enough to repair fractures and other common injuries. Irreconcilable destruction due to severe trauma, as well as treatments such as bone cancer tumor resection, are susceptible to improper healing if left to the natural course. The scaffold consists of natural and artificial components that are seeded with mesenchymal stem cells and placed in the defect. Within four weeks of placement of the scaffold, newly formed bones begin to integrate with old bone and within 32 weeks, complete unity is achieved. Further research is needed to fully characterize the use of cell-based therapy for the treatment of fractures.
Stem cells have been used to treat degenerative bone disease. The treatment that is usually recommended for dogs that have Legg-Calve-Perthes disease is to lift the head of the femur after degeneration has progressed. Recently, mesenchymal stem cells have been injected directly into the femur head, successfully not only in bone regeneration, but also in pain reduction.
Due to the general positive healing ability of stem cells, they are getting attention for the treatment of skin lesions. This is an important interest for those with reduced healing abilities, such as diabetics and those undergoing chemotherapy. In one experiment, the stem cell was isolated from the Wharton jelly from the umbilical cord. These cells are injected directly into the wound. Within a week, severe re-epithelialization of wounds has occurred, compared with minor re-epithelization of control lesions. This demonstrates the ability of mesenchymal stem cells in the repair of epidermal tissue.
Soft-palate defects in horses are caused by the failure of the embryo to completely seal in the midline during embryogenesis. This is often not found until after it gets worse because of the difficulty in visualizing the entire soft palate. This lack of visualization is also considered to contribute to a low success rate in surgical intervention to correct defects. As a result, the horse often had to be euthanized. More recently, the use of mesenchymal stem cells has been added to conventional treatments. After the surgeon has stitched the closed ceiling, the autologous mesenchyme cell is injected into the soft palate. Stem cells are found to be integrated into the healing tissue especially along the border with the old tissue. There is also a substantial reduction in the number of inflammatory cells present, which are thought to aid in the healing process.
Repair of ligaments and tendons
Autologous stem cell-based treatments for ligament injury, tendon injury, osteoarthritis, osteochondrosis, and sub-chondral bone cysts have been available commercially to practice veterinarians to treat horses since 2003 in the United States and since 2006 in the UK. Autologous stem cell-based treatments for tendon injury, ligament injury, and osteoarthritis in dogs have been available to veterinarians in the United States since 2005. More than 3000 horses and privately owned dogs have been treated with stem cells derived from autologous adipose. The efficacy of this treatment has been demonstrated in double-blind clinical trials for dogs with osteoarthritis of the hip and elbow and horse with tendon damage.
Horse races are very susceptible to tendon and ligament injuries. Conventional therapy is very unsuccessful in returning the horse to its full functioning potential. Natural healing, guided by conventional treatments, leads to the formation of fibrous scar tissue that reduces flexibility and full joint movement. Traditional care prevents a large number of horses from returning to full activity and also has a high back injury incident due to the rigid nature of the scratched tendon. The introduction of bone marrow cells and adipose derived stem cells, together with natural mechanical stimuli that promote tendon tissue regeneration. The natural movement promotes the alignment of new fibers and tendocytes with the natural alignment found in unharmed tendons. Stem cell care not only allows more horses to return to full duty and also greatly reduces the rate of back injury over a three-year period.
The use of embryonic stem cells has also been applied to tendon repair. Embryonic stem cells are shown to have better survival rates in the tendon as well as better migration ability to reach all areas of the damaged tendon. Overall improvement quality is also higher, with better tendon architecture and collagen forming. There was also no formation of tumors seen during the three month trial period. Long-term studies need to be done to check the efficacy and long-term risks associated with the use of embryonic stem cells. Similar results have been found in small animals.
Shared fix
Osteoarthritis is the leading cause of joint pain in both animals and humans. Horses and dogs are most commonly affected by arthritis. Regeneration of natural cartilage is very limited and there is no curative current drug therapy, but more visible to reduce symptoms associated with degeneration. Various types of mesenchymal stem cells and other additives are still being investigated to find the best types of cells and methods for long-term treatment.
Mesenchymal cells derived from adipose are currently the most commonly used for non-invasive harvesting. There have been many recent successes injecting mesenchymal stem cells directly into joints. This is a recently developed non-invasive technique developed for easier clinical use. Dogs receiving this treatment show greater flexibility in their joints and less pain.
Muscle Repair
Stem cells have been successfully used to improve healing in the heart after myocardial infarction in dogs. Adipose and stem cells of bone marrow derivatives are lifted and induced into the destiny of heart cells before being injected into the heart. The heart was found to have increased contractility and reduction in the damaged area four weeks after stem cells were applied.
Different experiments are being made for patches made of porous substances into which the stem cells are "seeded" to induce tissue regeneration of heart defects. The tissues are regenerated and the patches are well inserted into the heart tissue. It is considered because, in part, to increase angiogenesis and reduce inflammation. Although cardiomyocytes are produced from mesenchymal stem cells, they do not appear to be contractile. Other treatments that trigger the heart's fate in cells before transplantation have greater success in creating contractile heart tissue.
Improved nervous system
Spinal cord injuries are one of the most common trauma brought to an animal hospital. Spinal injuries occur in two ways after trauma: primary mechanical damage, and in secondary processes, such as inflammation and scar formation, in the days following the trauma. The cells involved in the secondary damage response secrete factors that promote scar formation and inhibit cell regeneration. Mesenchymal stem cells induced into the fate of nerve cells are loaded onto a porous scaffold and then implanted at the site of injury. Cells and scaffolds secrete neutralizing factors secreted by scarring cells and increase nerve regeneration. Eight weeks later, dogs treated with stem cells showed remarkable improvement over those treated with conventional therapy. Dogs treated with stem cells may occasionally support their own weight, which has not been seen in dogs undergoing conventional therapy.
Treatment is also in clinical trials to repair and regenerate peripheral nerves. The peripheral nerves are more likely to be damaged, but the damage effects are not as extensive as seen in spinal cord injury. Current treatment in clinical trials to repair broken nerves, with initial success. The stem cells are induced into the nerve injected into the broken nerve. Within four weeks, the regeneration of previously defective stem cells and fully formed nerve bundles was observed.
Stem cells are also in the clinical phase for treatment in ophthalmology. Hematopoietic stem cells have been used to treat corneal ulcers originating from several different horses. These ulcers are resistant to available conventional treatments, but quickly respond positively to stem cell treatment. Stem cells are also able to restore sight to a horse's eye with the release of the retina, allowing the horse to return to daily activities.
Keratoconjunctivitis Sicca (KCS)
The pre-clinical model of SjÃÆ'¶grens syndrome has reached its peak in allogenic MSCs that are planted around the lacrimal gland in refractory KSC dogs to current therapy. Significantly increased scores in ocular discharge, conjunctival hyperemia, corneal changes and Schirmer (STT) tear test were seen.
Society and culture
Marketing
In the late 1990s and early 2000s there were initial waves of companies and clinics offering stem cell therapy to desperate people, often with extraordinary claims about what stem cells can do. Such companies and clinics include Advanced Cell Therapeutics, Stowe BioTherapy, Cells4Health run by Cornelis Kleinbloesem, Beijing Xishan Institute for Neuroregeneration and Functional Recovery at Shijingshan run by Huang Hongyun, and EmCell in Kiev, Ukraine run by Alexandr Smikodub. These clinics make strong claims about their results, but rarely published protocols or rigorous studies showing that their therapies are safe and effective.
In 2012, a wave of both companies and clinics has emerged, usually located in developing countries where medicines are poorly regulated and offer stem cell therapy on medical tourism models. Like first wave companies and clinics, they have made strong similar claims and have not published their protocols or rigorous research; Mexico, Thailand and India have become the center of this activity, as well as South Africa.
See also
- autologous stem cell transplant
- Research Network for Cardiovascular Cell Therapy (CCTRN)
- Fetal network implants
- Human Stem Cells Institute
- Induced pluripotent stem cell
- Induction of stem cells
References
External links
Fiona Murray PhD, Debora Spar PhD "Bit Player Or Powerhouse? China And Stem-Cell Research", "New England Journal of Medicine" September 21, 2006. (Retrieved 30 July 2007)Source of the article : Wikipedia
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