01.09.2015

Natural cures for cancer in cats abdomen

Lung Cancer is the form of cancer that emerges from lungs and may also spread to different parts of the body. Several treatment options are available for lung cancer patients; however, these treatments do not provide instantaneous relief as well as cause negative side-effects.
This herb is known to display strong anti-oxidant properties, which help in boosting immune system in individuals suffering from lung cancer. This home remedy has been used extensively for treating skin infections, cardiovascular disease, as well as high cholesterol levels. Here we provide manually picked best quality and widescreen Desktop Backgrounds and HD Wallpapers. Cat Food Allergy or Intestinal Problems? My cat is approximately 9-10 years old, female, spayed and till six weeks ago never had problems other than occasional fleas. Cat Skin Rash Care and Treatment  Reader Question: What caused my cat to have bloody spots, and break out with bumps around her head? Sore Above Cata€™s Eye Not rated yetMy 10-year-old Persian Cat (female) developed a sore over her left eye.
The Cat Health Guide is not intended to replace the advice of a Veterinarian or other Health Professional. Fleas are the small microscopic organisms that survive on the blood of humans as well as animals. Fleas can lead to anemia, allergies and rashes (due to excessive scratching) in the animals. Lemon is slightly acidic in nature, which could be the reason for its efficacy in getting rid of the fleas.
Science, Technology and Medicine open access publisher.Publish, read and share novel research. Stem Cell Therapy for Cerebral Palsy – A Novel OptionAlok Sharma1, Hemangi Sane2, Nandini Gokulchandran1, Prerna Badhe1, Pooja Kulkarni2 and Amruta Paranjape3[1] Department of Medical Service and Clinical Research, Neurogen Brain and Spine Institute, Mumbai, India[2] Department of Research and Development, Neurogen Brain and Spine Institute, Mumbai, India[3] Department of Neurorehabilitation, Neurogen Brain and Spine Institute, Mumbai, India1. Bianco P, Riminucci M, Gronthos S, Robey PG, Bone marrow stromal stem cells: nature, biology, and potential applications. Orozco L, Munar A, Soler R, Alberca M, Soler F, Huguet M, Sentis J, Sanchez A, Garcia-Sancho J. Native to South and Central America, the medicinal properties of this herb have made it an excellent remedy for several conditions such as arthritis, cancer as well as infections. Skullcap is a part of the mint family and has been used extensively for treating cancer, atherosclerosis, hepatitis, insomnia, and inflammatory disorders. Ginger contains strong anti-inflammatory and antioxidant properties, which help destroying free radicals responsible for lung cancer. To make ginger tea at home, add small piece of ginger to a glass of water and boil this tea for 8-10 minutes. Garlic exhibits strong antioxidant properties that help in destroying harmful free radicals. You accept that you are following any advice at your own risk and will properly research or consult healthcare professional. Over the last few weeks, he developed a skin infection on the area beneath …Click here to write your own. It is important to arrest the growth of the fleas in the initial stage of the infestation otherwise it can be life threatening for your pet.While treating fleas it should be taken care that they are eliminated completely from the body of your pet, your house and from the garden. You will have to be very regular with the use of these treatments to get rid of the fleas completely.
Bathe your pet in white vinegar solution; add 6 cups of vinegar to two liter water and soak your pet in this solution for 20 minutes.
Wash the floor of your house, the walls as well as the furniture using strong solution of white vinegar and water. If bathing your pet with crystal salt isn’t possible every day then spray crystal salt solution over your pet’s body twice a day. If the problem is related to any hypersensitivity of your pet, completely isolate your cat from this allergen during treatment and avoid any exposure in the environment. I have a cat named Tess that is 17 years old, female, black domestic short haired and is having major skin problems right now.It started around her eyes, which were inflamed, missing fur and constantly runny. IntroductionDiscovery of stem cells by James Till and Ernest McCulloch in 1961, stands as one of the most remarkable medical-research achievements of the 20th century. Stem cells derived from human fetal membranes display multilineage differentiation potential.
Susceptibility of human fetal mesencyhmal stem cells to Kaposi sarcoma-associated herpesvirus. Human herpesvirus-6 encephalitis after unrelated umbilical cord blood transplant in children.
JC Virus Leuko-Encephalopathy in Reduced Intensity Conditioning Cord Blood Transplant Recipient with a Review of the Literature. Haematopoietic progenitor cells from adult bone marrow differentiate into cells that express oligodendroglial antigens in the neonatal mouse brain. Human bone marrow stem cells exhibit neural phenotypes and ameliorate neurological deficits after grafting into the ischemic brain of rats. Although lung cancer can affect individuals of any age, it mostly affects people older than 40 years of age.
Health experts highly recommend the use of cats claw in conjunction with traditional cancer treatments. However, ginger also exhibits blood-thinning properties, therefore, it is advisable that you inform your doctor before consuming ginger. This is because fruits and vegetables contain high concentrations of vitamins that destroy free radicals. Also, treat your other pets and family members for fleas so that the problem does not recur. A word of caution; do not use white vinegar for treating fleas if your pet has fresh rashes on its body due to scratching (fleas result in intense itching). However, diatomaceous earth is also known for helping in pest control.To treat fleas use only the unrefined version of the earth. The fleas react negatively to the bitter taste of crystal salt and cannot exist in such harsh environment. Sprinkle crystal salt on the floor of your house, on the furniture as well as on the carpet. An approved treatment for such cat skin allergy conditions are the use of anti-histaminic drugs along with corticosteroids. For a while she could barely open her eyes or even look up, which is very unusual for her since she is so friendly and affectionate.
Research studies have indicated that this herb exhibits anti-cancer properties due to presence of flavonoids. Fruits and vegetables that possess highest amounts of vitamins include citrus fruits, broccoli, spinach, kiwifruit, collard greens and bell peppers. Please let us know about the age of the cat, breed, when any cat skin symptoms began, have they changed over time, if your cat is indoor or outdoor, the presence of other pets, changes in your cats routine, bathing frequency, or anything else that will help us understand your cat's medical history, any tests and results.
They rapidly multiply in number and become the cause of various bacterial and viral infections in your pets. In the meantime, prepare pouches of raw (and peeled) garlic and place them in all the corners of the house.
You can also mix lemon juice with your pet’s shampoo to treat the fleas.Give bath to your pet every day using lemon water. Sprinkle the earth in your garden as well as in your backyard to prevent infestation of the fleas. However, these should only be only be administered after confirmation of the specific cause of the condition.Other therapeutics and products you are using for your cat including antibiotics and Frontline spot etc, should be reviewed. According to a research study conducted on human lung cancer cells, it was noted that skullcap induced death in cancerous cells. In addition to that, you should also consume fish as it contains high amounts of omega 3 fatty acids, which help in destroying free radicals. Pour the treated water in a bathtub and add some warm water to it.Bathe your pet with this water.
You can also spray lemon water over your pet three times a day to prevent the infestation of fleas. Pour the earth in between the cracks in the walls and the floors to avoid the fleas from entering your home.
We took her to the vet and they informed us that it could be a reaction to drywall (we were doing some renovations in our bathroom), so we gave her antibiotics and antihistamines. Administration of autologous bone marrow derived mononuclear cells in children with cerebral palsy. Prior to using skullcap in the treatment of lung cancer, seek advice from your doctor regarding suitable dosage. Other foods that contain omega 3 fatty acids include flaxseed, sunflower seeds, olive oil and nuts. Garlic has antifungal and antibacterial properties that effectively eliminate the micro-organisms responsible for various infections.
In place of your cat's current shampoo, consider a natural product such as Stinky Paws Pet Wash.Just in case the tests for hypersensitivity and an auto immune disease (allergy) come back negative, I suggest that you take your cat for a detailed biopsy, where a small skin sample will be tested.
Capecchi, and Oliver Smithies were jointly awarded a Nobel Prize in 2007 for their contribution in introducing specific gene modifications in mice by the use of embryonic stem cells. Please include information such as breed, age, sex, history, changes in behavior, products used etc.We will try and respond as quickly as possible. The crystal salt treatment should be done every day for a couple of weeks to avoid re-attack of fleas.
Then they said that it is an autoimmune disease so they prescribed corticosteroid cream and injected him with steroid. I fear, that this might be some kind of neoplasia (cat skin tumor) related to the immune system and skin.Best of luck to you and your cat.
Wash your clothes, draperies, bed sheets and even yourselves in neem water for getting rid of the fleas completely. Gurdon and Shinya Yamanaka were also jointly awarded a Nobel Prize for discovering that mature cells can be reprogrammed to become pluripotent cells. There is a new one at his groin and it is bloody reddish shaped like the north american continent. After a while she seemed to be okay so we stopped with the pills, then the real problems began.She began furiously licking and pulling her fur out.
I noticed it around the inside of her legs and then it began to spread to her other legs, butt and chest. It was a long-standing belief that cells of the central nervous system once damaged cannot be regenerated. We took her to the vet again and they gave her steroids and antibiotics, as well as a squeezing of her anal glands (which were very swollen). The medical science of stem cells has finally made restoration of CNS possible which has changed the old concept of medicine. After that she would come out from under my bed and visit, eat, drink, use the litter box etc.
Not too long ago, this therapy was hamstrung by various controversies, ethical and moral issues. But, tremendous progress of research in this field has finally led to its translation from laboratory to innovative cellular therapies. A variety of cells including embryonic stem cells, adult stem cells, umbilical cord blood cells and induced pluripotent stem cells have been explored as a therapeutic alternative for treating a broad spectrum of neurologic disorders including stroke, Alzheimer’s, Parkinson’s, spinal cord injury, cerebral palsy etc. Such skin conditions are usually caused by different allergens, including chemicals, drugs, food components, bugs and even through exposure to sun light. She continues to pull out her fur, leaving her legs patchy, pink and scabby, as well as her chest. She still comes out to eat and drink and all that but now she hides from us hours at a time. It is essential to select suitable cells depending on the nature and status of neurological dysfunctions to achieve optimal therapeutic efficacy.
Along with the selection of cells, the route of administration also plays an important role to maximize the clinical therapeutic effect of the cell therapy. Tess was rescued from a shelter when she was one and was a bit of a delinquent when we first got her but eventually she calmed down and turned into one of the most lovable cats out there. Numerous preclinical studies have been carried out to study the safety of intrathecal, intravenous and direct cerebral implantation. I love her dearly and I don't want to say goodbye even if she is 17.We don't understand why she is in so much discomfort, if it's stress related from the initial pill popping, the renovations from months prior or if she's falling apart because she's so old. A plethora of published literature is also available to provide evidence of stem cells initiating functional restoration of CNS. The postulated mechanisms of action involved are neuromodulation, neuroprotection, axon sprouting, neural circuit reconstruction, neurogenesis, neuroregeneration, neurorepair, and neuroreplacement. Our last cat who died stopped all that altogether, though she had cancer and deteriorated far quicker.
In view of the fact that stem cell therapy has a promising therapeutic potential in the treatment of neurological disorders, it is important for all the professionals in the medical field to understand the concepts of this upcoming therapeutic strategy.


In this chapter, we have focused on stem cell therapy for Cerebral Palsy (CP) which is a heterogeneous group of neurological disorders mainly observed in infants. It's not skin cancer since she has no bumps, tumors and it's not like this is something she's dealt with before. You could try an oral steroid like prednisolone, which would allow you to find the lowest, effective dose for Faith and reduce the possibility of side effects developing.
The survival of CP children has increased due to advanced modern medicine which has led to their growing population. CP involves impairment of movement, muscle function, and cognitive functioning and the effects range from mild to severe. You must understand that I don't want any documents that show how bad she is, just in case she has to be put down and I'm left to deleting the pictures. No biological intervention has been effective for CP and the standard approach is limited to supportive management strategies which do not address the core issue of neural tissue damage. Currently, stem cell based strategies have garnered attention due to their ability of neuroregeneration and neuroprotection in CP.
We have discussed the clinical aspects of stem cell therapy in cerebral palsy supported by various human case studies and clinical trials. This can possibly be a reaction to therapy administered for the eye condition, but most likely is an underlying immune mediated generalized problem. We have also enumerated our experience and results wherein our subjects were administered autologous bone marrow mononuclear cells. The worsening of this type of condition to such a level as you describe is related to age as a factor.Older cats need more attention and care. Stem cellsStem cells are defined as “cells that have the ability to renew them continuously and possess pluripotent or multipotent ability to differentiate into many cell types.” [4]These cells exhibit a unique property of “plasticity” where in cells isolated from one tissue convert to cells of different tissues by crossing lineage barriers and adopting the expression profile and phenotype of cells that are unique to other tissues. A thorough diagnostic approach is needed for making a decision regarding this condition and a possible treatment plan for stopping the cat pulling fur problem.I recommended that you take your cat for laboratory tests that can check for an immune system disturbance.
Start with sensitivity tests and additional hypersensitivity tests (in vitro or intradermal). Totipotent cells: These cells have the ability to differentiate into all possible cell types of the human body including extra embryonic and placental cells. The level of circulating eosinophills should be carefully monitored and once the status of the immune system is revealed, a specific therapy can be initiated.A Specific therapy for this type of condition typically involves the use of antibiotics, steroids, aurthioglucose (gold salts) and endocrinal restrictive agents. Pluripotent cells: These cells have ability to differentiate into any of the three germ layers viz. Unipotent cells: These cells have the ability to produce cells only of their own type, but are capable of self-renewal to be classified as a stem cell. Invitro, they can be indefinitely maintained and expanded as pure populations of undifferentiated cells.
They form teratomas which have the potential to degenerate into malignant teratocarcinomas [8] The likelihood of development of tumors in children cannot be overlooked as they have many years of life ahead of them for the tumor formation to occur. Fetal Stem Cells: These cells are isolated either from the aborted fetus or from the extra embryonic structures of the fetal origin such as the amniotic fluid and placenta.
Non-haemopoietic mesenchymal stem cells (MSC) are also found in the first trimester fetal blood. They consist of embryonic stem cell-like and other pluripotential stem cells, which can give rise to hematopoietic, epithelial, endothelial, and neural tissues. The protocols and guidelines for collection and retrieval of cells are still being standardized. Other disadvantages of use of UCBCs are limited by the fact that minimum necessary dosage of cells for cell engraftment is 1 ? 107 cells per kilogram which includes the total nucleated cell fraction along with stem cells. Thus, the available dose of autologous cells obtained at birth may be insufficient for transplantation at an older age of the child [13]. Amount of stem cells found in the cord blood is 10% less than that obtained from the bone marrow. Induced pluripotent stem cells are non-pluripotent adult cells (somatic cells) which have been genetically reprogrammed to form pluripotent cells.
The availability of iPSCs is particularly advantageous for research involving neurological diseases, since it is difficult to obtain diseased tissue sample for study from living patients.
They include hematopoietic stem cells, bone marrow derived stem cells, adipose tissue-derived stem cells, neural stem cells amongst others [18] Adult stem cells are found in almost all the tissues of the body and help to maintain and repair organs and tissues throughout a person's life. These cells are majorly found in the bone marrow, brain, skeletal muscle, liver, pancreas, fat, skin and skeletal muscle.
The different types of adult stem cells include multipotent adult progenitor cells, oligodendrocyte progenitor cells neural stem cells, glial progenitor. Major sources of adult stem cellsBone marrow: Anterior or posterior superior iliac crest is the preferred site for the bone marrow aspiration.
If bone marrow cannot be obtained from the iliac crest due to positioning difficulties or obesity, sternum may be used in adults.
Cells isolated from the bone marrow not only differentiate into blood cells but also into neural tissues. The hematopoietic stem cells (HSCs) are the blood cells which give rise to the myeloid and lymphoid lineages.
HSCs also have a potential to transdifferentiate into various nonhematopoietic cell lineages especially neural lineage.
It is generally believed that BMMSCs are negative for hematopoietic cell markers such as CD14, CD34, c-kit, SCA1. They promote angiogenesis, mediate vascular repair, and express several cytoprotective growth factors and cytokines. These cells are also safe and due to its easy availability they are most preferred for cellular therapy. These cells are used for the treatment of various neurological disorders such as cerebral palsy, stroke, Parkinson’s, Spinal cord injury, etc. They can differentiate into several lineages, including adipose cells, chondrocytes, osteoblasts, neuronal cells, endothelial cells, and cardiomyocytes.
In experimental cerebral palsy models, infusion of adipose derived stem cells has shown to improve physical activities and cognitive deficits.
These cells are readily obtained from routine dental procedures such as removal of impacted third molars, deciduous teeth and have been shown to possess properties similar to neural stem cells and mesenchymal stem cells.
Menstrual Blood stem cells: Recently, stem cells have been identified from the endometrial tissue.
Hematopoietic stem cells obtained from PB by leukapheresis have been used for transplantation as an alternative to bone marrow-derived stem cells (BM-stem cells). Various routes of administration of stem cells for cerebral palsyThe appropriate route of cell administration is essential prerequisite for the success of cellular therapy.
For the treatment of cerebral palsy, cells are injected via various routes such as intrathecal, intravenous and intracerebral.
Intrathecal administration: Intrathecal administration of cells involves delivery of cells via lumbar puncture.
This mode of injection allows efficient delivery of cells and the possibility of migration of cells to the tissues other than the damaged ones is avoided. In case of cerebral palsy, it is considered to be the safe, feasible and efficacious route of administration. In cerebral palsy, studies have shown that this route of administration results in positive functional outcomes.
Studies have shown that on administering cells intravenously, few cells reach the damaged site while a majority of cells get trapped in the lungs.
Pulmonary passage could be one of the major hindrances for intravenous administration of stem cells.
Hence, for effective result of intravenous stem cell transplantation, it is necessary to increase the number of cells injected. This leads to migration of cells to the areas of ischemia but the outcome is not as remarkable as compared to the other minimally invasive procedures. Additionally, in CP the injury of the brain is diffused and a local injection could be focused on a particular area which might not be as effective. Mechanism of action of stem cells in cerebral palsyTo understand the mechanism of action of stem cells in the treatment of cerebral palsy, it is important to understand the empirical neuropathophysiology. In spite of the vast and varied etiology; underlying cellular mechanisms, that cause the morbidity or mortality associated with cerebral palsy, are tissue damage caused by hypoxia and ischemia.
The clinical manifestations of this cellular damage, depends on a range of factors including the time of insult, the severity of insult and cause of the insult.
Recent preclinical, immunohistochemical and imaging evidence suggests periventricular white matter injury (PWMI), particularly damage to oligodendrocytes (OLs) as a primary cause of cerebral palsy [40,41,42]. PWMI is a spectrum ranging from cystic focal necrotic lesions, periventricular leuckomalacia (PVL) to specific cortical scarring in the deep regions of sulci, Ulegyria to diffuse myelination disturbances. Oligodendrocyte progenitors are abundantly present in the subventricular and periventricualr zones, therefore damage to these cells is seen as PVL in neuroimaging investigations. The extent of the damage to the white matter and its consequences are dependent on the developmental stage at which the damage occurred, brain vascularization and the type of tissue[43].
Figure 2.Phases of Oligodendrocyte developmentVascularization of the brain begins as early as 28th day of gestation with the formation of carotid arteries, followed by the large arteries, their branches, communicating arteries, long penetrating arteries and ends with the formation of short penetrating arteries in the post term period.
Damage at pre term leads to focal cystic necrosis in the vascular end zones of the long penetrating arteries causing PVL, damage at term leads to tissue injury at the border zones of the long and short penetrating arteries giving rise to Ulegyria and damage at post term leads to diffuse myelination disturbances caused at the vascular end zones of short penetrating arteries [44].
Subsequently most vulnerable cells, precursors of Oligodendrocytes (OLs), undergo necrosis through apoptosis.
Oligodendrocytes evolve through an established lineage of OL progenitors to pre OLs to immature OLs to mature OLs. Other cell types and mechanisms that contribute to pathophysiology of CP are axonal damage and microglial activation [45]. Following this primary insult to the nervous tissue, activation of glial cells leads to secretion of various chemical mediators of tissue necrosis in the neural microenvironment, leading to secondary white matter injury.
These mediators are Reactive oxygen and nitrogen species, glutamates, adenosine and inflammatory cytokines like Tumor necrosis factor alpha (TNF-?), interferon gamma (INF-?), Interleukin -1 beta (IL-1?) and superoxide radicals [46]. Hence, stem cell intervention is more successful in these children as the integration of new cells in the brain to carry out the repair process is more effective [47]. Stem cell possess the capacity to home onto the injured sites of brain, as guided by chemo attractant pathway [48]. The effects of cellular therapy are twofold, enhancing the brain tissue repair caused by various paracrine mechanisms and regeneration of neural tissue. Stem cells help in modifying the microglial response by exhibiting immunomodulatory, neurotrophic properties and enhance axonal sprouting. Various neurotrophic factors secreted by the stem cells are connective tissue growth factor, fibroblast growth factor 2 and 7 that are responsible for cell proliferation, interleukins responsible for cytoprotection [49,50,51]. Stem cell therapy restores lost myelin by replacing dead cells with new oligodendrocytes and their progenitors. Indirectly, it may also support their survival by introducing other cell types able to restore missing enzymes to an otherwise deficient environment [47]. Stem cell therapy also has an anti-inflammatory effect on the neural microenvironment as they reduce the levels of TNF-?,IL-1?, IL-1?, IL-6 and increased levels of IL-10 [52]; therefore, enhancing the endogenous brain repair.
Stem cells also secret various growth factors like vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), brain fibroblast growth factor (bFGF). These growth factors initiate neoangiogenesis and induce secretion of hormones like erythropoietin. The cascade events triggered due to these lead to formation of new vessels as well increased bold flow.
Improved blood circulation of the brain thus helps retrieving the lost tissue functions [50].3.
Published literatureSeveral preclinical experiments on animal models of cerebral palsy have been carried out to demonstrate the potential of cell transplantation to minimize damage and promote recovery. However, limited clinical trials have been initiated to study the effect cell therapy in humans. Human umbilical cord blood cells (hUCBCs) have been explored to a great extent in cerebral palsy.
They protect the mature neurons in the neocortex from injury, bring about near-normalization of brain damage in the subventricular zone (SVZ) leading to significant improvement in behavioral functions.
The long lasting effect of these cells is due to the paracrine effects of hUCBCs which stimulate recovery in the injured brain and protect against further brain damage. The dimensions of cortical maps and receptive fields, which are significantly altered after injury, are largely restored.
Additionally, the lesion induced hyper-excitability is no longer observed in treated animals compared to control animals. The results demonstrate that hUCB cells reinstall the way central neurons process information by normalizing inhibitory and excitatory processes. Park et al reported clonal neural stem cells (NSCs) when transplanted into brains of postnatal hypoxic-ischemic (HI) injury mice, home preferentially to and integrate extensively within the ischemic areas.
They observed that cells migrated to the lesion site, remained undifferentiated at day 10, and differentiated into oligodendrocyte and neurons at day 42. Although grafted cells finally die there few weeks later, this procedure triggered a reduction in lesion size and an improvement in memory performance compared with untreated animals. But, similar results are difficult to replicate in human cases since the intervention always, cannot be carried out immediately post injury.


Based on this observation, it can also be concluded that earlier the intervention, better is the outcome. They underwent transplantation of neural progenitor cell (NPC) derived from aborted fetal tissue.
After 1 year, the developmental level in gross motor, fine motor, and cognition of the treatment group was significantly higher compared to the control group. These results suggested that NPC transplantation is a safe and effective therapeutic method for treating children with severe CP. On follow up, they observed an increase in the GMFM scores and language quotients compared to the control group. No adverse events were recorded indicating that NSC-like cells are safe and effective for the treatment of motor deficits related to cerebral palsy. They observed improvement in motor and cognitive dysfunction in children with CP, accompanied by structural and metabolic changes in the brain. They found that this therapy was safe, feasible and led to functional improvements in children which was seen by the change in GMFCS. At 2-months follow-up the boy's motor control improved, spastic paresis was largely reduced, and eyesight was recovered, as did the EEG. At 40 months, independent eating, walking in gait trainer, crawling, and moving from prone position to free sitting were possible, and there was significantly improved receptive and expressive speech competence (four-word sentences, 200 words).
This suggested that autologous cord blood transplantation could be a treatment alternative for cerebral palsy. She was treated with multiple times of intravenous and intrathecal administration of MSCs derived from her young sister and was followed up for 28 months. On follow up, they recorded a significant improvement in motor, sensory, cognitive, and speech.
Hence, concluding that intrathecal infusion of autologous BMMNCs is feasible, effective, and safe in CP patients. Six months after the treatment, both cases showed significant functional outcomes which was supported by improvement in PET CT scan.
Ongoing trialsCurrently, there are five clinical trials on stem cell therapy for cerebral palsy registered in clinicaltrials.gov. One of the studies is a combination of phase 1 and phase 2 while the other is a combination of phase 2 and phase 3.
2 studies are from Iran, one evaluating the side effects of bone marrow derived CD133 cells transplantation in cerebral palsy patients and the other studying the safety of multiple intrathecal injections of bone marrow derived CD133 cells.
A study from USA is based on evaluating the safety and effectiveness of a single, autologous, cord blood stem cell infusion for the treatment of cerebral palsy in children. Administration of autologous bone marrow derived mononuclear cells in children with cerebral palsy.Sharma et al, carried out a study on 71 children, wherein they administered 20 cases of cerebral palsy with autologous bone marrow mononuclear cells, intrathecally. Symptoms commonly observed in them were delayed milestones, spasticity, motor impairment, ambulation deficits, cognitive impairment, swallowing and speech problems etc. Autologous bone marrow MNCs were selected as they are easily obtainable, safe and do not involve any ethical issues. As discussed earlier, intrathecal route of administration is a minimally invasive, safe and an effective procedure as compared to other routes. Studies have also proved that a mixture of cells exhibits more benefits as compared to a single sub fraction of cells. On the day of the transplantation, bone marrow was aspirated under general anesthesia in the operation theatre with aseptic precautions. Approximately, 100 ml of bone marrow (varying between 80 ml and 100 ml, based on the age and body weight) was aspirated from the region of anterior superior iliac spine using the bone marrow aspiration needle and collected in the heparinized tubes. The aspirate was then transferred to the laboratory where the mononuclear cells were separated by the density gradient method. The separated autologous BMMNCs were immediately injected on the same day, intrathecally using an 18G Touhy needle and epidural catheter at the level between fourth and fifth lumbar vertebrae.
Patient was monitored for any adverse events.On mean follow up of 15 months ± 1 month post stem cell administration, improvement was observed in 85% cases. Some minor side effects such as headache, nausea and vomiting were experienced by few children who were self-limiting (resolved within a week) and treated with medications. None of them showed any deterioration on the GMFCS [78]We are also currently conducting a clinical study to assess the efficacy of autologous BMMNC in 64 patients with CP.
The unpublished data analysis have shown preliminary results as improvement in oromotor skills, speech, neck holding, sitting, standing and walking balance and significant reduction in muscular tone and dystonic movements. These changes were observed in all types of cerebral palsy over 6 months with varied follow up periods. Oromotor skills (75%), speech (64%), neck holding (100%),Sitting balance (67%), standing balance(67%), walking balance (67%), ambulation (30%), leg movements (54%), overhead movements (38%), distal hand movements (69%), upper limb spasticity (38%), Lower limb spasticity (38%), trunk muscle tone (36%), trunk dissociation (30%)Percentage improvement noted in patients of quadriplegic cerebral palsy was as follows.
Oromotor skills (58%), speech (40%), neck holding (94%),Sitting balance (48%), standing balance(27%), walking balance (21%), ambulation (13%), involuntary movements (25%), upper limb spasticity (51%), Lower limb spasticity (50%), trunk muscle tone (36%) Percentage improvement noted in patients with other types of cerebral palsy was as follows.
Objective imaging evidenceVarious clinical outcome measures have been devised to measure changes in sensory, motor, cognitive, perceptual and Behaviour functions in CP. MRI scans not only help reveal the underlying pathology of CP, but it also correlates with the clinical findings. Principle mechanisms underlying the benefits of cellular therapy are the changes brought about in the microenvironment of cells reducing cell necrosis, ischemia and hypoxia.
These changes therefore cannot be measured on a plane MRI and hence it is not a sensitive tool to monitor the effects of stem cell therapy. Functional neuroimaging on the other hand may be an appropriate option to monitor the finer changes at cellular level. The basic principle underlying the functional neuroimaging of the brain is that the cerebral blood flow and metabolism is associated with neuronal activity.
Measurement of the tissue function is therefore a preferred outcome measure to monitor the effects of cellular therapy.
Positron Emission Tomography – Computed Tomography (PET – CT) is one of the techniques of functional neuroimaging that measures the metabolism of the nervous tissue in terms of Fleuro-deoxy glucose (FDG) uptake. FDG is a radioactive glucose analogue that undergoes glycolysis in the same manner as that of glucose. Once it has been metabolized to FDG – 6 – Phosphate it cannot be further metabolized and is trapped inside the cell due to the impermeability of the cell membrane for this molecule. Photons emitted by this radioactive isotope are then measured to identify concentration of FDG in the nervous tissue [84].
This is expressed as a ratio of the actual uptake and the calculated presumed uptake of FDG, standard uptake value [85]. Because of its ability to measure the finer changes in tissue metabolism, FDG PET-CT holds a great potential as a monitoring tool. Various guidelines are available for appropriate standardization, image acquisition and interpretation during PET-CT scanning. The tissue metabolism of 18F-FDG is the same in adult and children and the dose administered in children is “as low as reasonably achievable”. Various adjustments with regards to scanning technology and measurement period are made to enhance the quality of the image with the administered dose [89]. PET-CT is sensitive to measure the cellular changes and it is a standardized imaging modality which makes it a good monitoring tool to assess the effects of cellular therapy. In our previous case studies involving cerebral palsy patients treated with autologous bone marrow derived mononuclear cells (BMMNCs), the clinical outcome was correlated with changes in the PET scan. In one case of a 20 year old CP patient with co morbid intellectual disability, a repeat PET-CT scan showed significant increase in the FDG uptake in various affected areas of the brain, which correlated with the clinical improvement in social behavior, balance and motor control.
However the MRI remained unchanged (76).In another case of a 2 year old child with cerebral palsy, we observed similar correlation of clinical improvement with the PET-CT changes in metabolism.
These clinical changes were synonymous with the increased FDG uptake in the bilateral mesial temporal structures, right basal ganglia, frontal, parietal, temporal and occipital lobes.
Functional MRI is also one of the emerging techniques to study the functional outcome of the intervention.
The technique of fMRI is based on Blood oxygenation level dependent (BOLD) contrast between rest and activated states of human brain.
Hence, fMRI may be effectively used to monitor the therapeutic outcome of stem cell therapy and should be studied further. Role of rehabilitation in combination with stem cell therapyFor a long time, rehabilitation has been the standard approach for cerebral palsy.
The goal of rehabilitation in cerebral palsy is to develop coordination, build strength, improve balance, maintain flexibility, optimize physical functions, manage spasticity and maximize independence.
Various therapeutic regimens aim to enhance particular clinical, functional and psychosocial consequences of CP.
Physiotherapy, makes use physical modalities to muscle spasticity, increase flexibility, balance and co-ordination, build strength and enhance function.
Multiple medical and surgical regimens are also instituted to deal with these physical impairments. Botox injections are most commonly used to reduce spasticity of the muscles, but the effects are short lived. A variety of surgical techniques are utilized to correct deformities.Occupational therapy is focused at therapeutic regimens to improve cognitive abilities of the child and increase participation in activities of daily and social living. Children with CP most often present with poor oromotor control and speech disorders, speech therapy aims at correcting these impairments.
It helps to improve the quality of life by addressing co-morbid psychological disturbances and cognitive impairments. All of the rehabilitative modalities face the fundamental limitation of inability to repair the damage to the nervous tissue.
Wright and Nicholson and Sommerfeld et al have demonstrated that physical therapy alone does not show a consistent benefit in cerebral palsy. It also increases angiogenesis and oxygen supply to the brain thereby improving the cognitive function.
Regular exercise induces suppression of pro-inflammatory cytokines and up regulation of anti-inflammatory cytokines in various tissues of the body including brain. In addition, mobilization of stem cells, enhanced homing, improved angiogenesis exercise also exerts immunomodulatory effects. Exercise and rehabilitation has a synergistic effect for the benefits of cell transplantation.
Although cellular therapy for cerebral palsy has moved from the preclinical studies to bedside therapy; evidence remains inconclusive regarding multitude of variables. These variables are pertaining to cerebral palsy and cellular therapy.Cerebral palsy is a heterogeneous group of disorders. Pre-clinical models of effects of cellular therapy in cerebral palsy are far from the ideal state and show benefits only in acute injury.
Majority of the human application of stem cells in cerebral palsy is for individuals who already have established pathology, hence at a chronic stage. Animal models of chronic injury are therefore required to study the efficacy and mechanism of action of stem cells.
The individuals suffering from cerebral palsy are from various age groups, and present with varied kinds and severities of clinical manifestations; there is only a limited evidence about which of these groups will benefit the most from cellular therapy. Only preliminary evidence using basic research methodologies is available for the effects of cellular therapy in humans. We require more double blind, randomized, multicenter controlled clinical trials to prove the safety and feasibility of stem cells. The evidence available is heterogeneous in methodology, patient population, outcome measures and cellular therapy provided. Stem cells provide their beneficial effects through numerous mechanisms; it is difficult to underpin the exact mechanism of action of stem cells. Types, sources and numbers of cells administered, frequency of transplantation, time of transplantation are concerns which require attention imperatively.
It is important to not only conduct more trials but also to standardize research protocols to allow comparison.
Comparative studies will help in establishing the most effective cell based therapy for cerebral palsy.Apart from these issues, development and validation of outcome measures to obtain evidence of the efficacy of intervention is very important.
Modalities should be developed to study the effect of cell transplantation at a cellular level. Outcomes that can successfully assess these cellular changes are measuring the serum, plasma and cerebrospinal fluid biomarkers, which are invasive. PET-CT scan has been used as an outcome to assess the effects of cellular therapy however it is required to further explore its various components in depth. It is therefore necessary to explore how functional imaging can provide us a better understanding of the cellular mechanisms. ConclusionStem cell therapy has been extensively studied but still needs to be standardized before it becomes a definitive treatment modality. Autologous BMMNCs are safe and feasible option but their effectiveness needs more clinical trials.




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