What are the different types of stem cells?
There are many types of stem cells, but broadly they are classified into 3 types:
Embryonic stem cells
Embryonic stem cells (ESCs) are stem cells derived from the undifferentiated inner mass cells of mammalian embryos in the blastocyst stage on the fifth and sixth day after fertilization. They are derived from embryos that have been fertilized in vitro (in laboratory) in an in vitro fertilization clinic. Embryonic stem cells are distinguished by two distinctive properties: their pluripotency i.e their ability to form any cells of the body and their ability to multiply indefinitely. Because of these properties, embryonic cell therapies have been proposed for regenerative medicine and tissue replacement after injury or disease. These cells are grown in culture medium in the laboratory at a suitable temperature and humidity where they divide and multiply indefinitely.
Some of the advantages of embryonic stem cells are:
Embryonic stem cells are able to form any cell type of the body, and are more versatile than other stem cells
These cells are considered immortal as they can be maintained in undifferentiated state for a very long time in controlled conditions.
Some of the disadvantages of embryonic stem cells are as follows:
These cells can sometimes divide uncontrollable, forming tumors and growths madeof unwanted tissues.
Human embryos are destroyed in the process of collecting these cells.
These cells are related with many immunological rejections that results from the expression of MHC proteins.
It is very expensive.
Umbilical cord stem cells
Umbilical cord is a rich source of stem cells which are either obtained from umbilical cord blood or Wharton Jelly. There are a variety of stem cells which can be obtained from the Umbilical cord namely hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs), and unrestricted somatic stem cells (USSCs) and other non- hematopoietic stem cells. Use of these cells has been currently approved for treatment of leukemias, lymphomas, anemias and inherited metabolic disorders. Numerous clinical trials are being conducted to study their potential in disorders like cerebral palsy, autism, ALS, etc.
The umbilical cord is collected and stored in a cord blood bank which is either public or private bank.
The advantages of using umbilical cord derived stem cells are:
It is a non-invasive source and can be obtained from the umbilical cord immediately after birth.
Available in vast abundance; thousands of babies are born each day and the umbilical cord and placenta are discarded as waste.
Despite its high content of immune cells, it does not produce strong graft-versus- host disease
Therefore, cord blood grafts do not need to be as rigorously matched to a recipient as bone marrow grafts.
Along with these advantages there are also few disadvantages of using umbilical cord stem cells such as:
Engraftment of transplanted cells is slow as compared to other cell sources
The volume of cells obtained from one umbilical cord is limited and low. Also, additional cell dose cannot be obtained.
Few occurrences of infection have been recorded on use of these cells.
There may be storage related issues such as loss of viability due to long term storage, Cost related to long term storage, etc
Quality control
Adult stem cells
Stem cells are found in our body during all stages of life, number of stem cells and their ability to differentiate into different cell types differs as per the age of the person. Different types of stem cells are available in the body. There are stem cells that are tissue specific and are committed to differentiate only in one type of tissues. But adult stem cells can also be multipotent, with ability to be able to differentiate into different cell types.
Niches are the specific areas from where these cells can be procured. Adult stem cell niches have been found in most organs of the human body, eg. liver, brain, bone marrow, fat tissue, heart, nasal ensheathing cells, tooth pulp tissue etc. Whenever there is an injury or wear tear in the body these cells initiate the repair process. These are not only the cells from that particular tissue but the stem cells from bone marrow are mobilized to the peripheral blood and to different organs. This repair process is their primary role. Adult stem cells are a non-controversial and safe option for use in human subjects as they can be used autologously.
To date, published scientific literature indicates that adult stem cells have been derived from brain, bone marrow, peripheral blood, dental pulp, spinal cord, blood vessels, skeletal muscle, epithelia of the skin and digestive system, cornea, retina, liver, and pancreas; thus, adult stem cells have been found in tissues that develop from all three embryonic germ layers. However they cannot be procured easily from all of these sources; most common sources are bone marrow, abdominal fat and dental pulp.
Most of the beneficial effects of adult stem cells are also because of the paracrine effects of these cells on surrounding tissues. Paracrine effects are the changes induced in the functioning of cells surrounding these stem cells in the body. These are mediated through different chemicals secreted by the tissue. These paracrine effects are reduction in inflammation, neo-angiogenesis, immunomodulation and stimulation of local resident stem cells.
Bone Marrow Derived Cells
Different types of stem cells have been found to be present in the bone marrow, which differ in their potential to differentiate and form cells from one or more germ layers.
Initially, the bone marrow was thought to contain only hematopoietic stem cells. However, increasingly, evidence is pouring in regarding the heterogenous population of cells having varying plasticity. Mononuclear cells obtained from the bone marrow are a mixture of heamatopoietic stem cells, mesenchymal stem cells, very small embryonic like stem cells etc. Therefore these is a mixture of different types of stem cells in this tissue fraction.
Adipose tissue derived cells:
The adipose tissue (AT) is a highly complex tissue. It consists of mature adipocytes, preadipocytes, fibroblasts, vascular smooth muscle cells, endothelial cells, resident monocytes/macrophages and lymphocytes. Adipose tissue provides a rich source of pluripotent stromal cells.
Adult stem cells have no ethical issues as associated with embryonic- and fetal-derived cells and are less susceptible to malignant changes and genetic abnormalities.
What are stem cells?
Stem cells are the fundamental elements forming all the tissues of the human body. They are unique cells with an ability to rapidly multiply and convert into any type of tissue in the body. The main purpose of these cells is to regenerate, repair and replace damaged tissue. They are naturally capable of travelling towards the damaged areas and start the repair process.
Types of Stem Cells
Source
Embryonic stem cells (ESCs):-
Embryonic stem cells (ESCs) are stem cells derived from the undifferentiated inner mass cells of mammalian embryos in the blastocyst stage on the fifth and sixth day after fertilization.
Umbilical cord stem cells:
Umbilical cord is a rich source of stem cells which are either obtained from umbilical cord blood or Wharton Jelly.
Adult stem cells:
Stem cells are found in our body during all stages of life, number of stem cells and their ability to differentiate into different cell types differs as per the age of the person.
Receiver
Autologous stem cells:
Autologous stem cells are those which are obtained from the patient’s own body. They may be obtained from
Bone Marrow
Abdominal Fat
Umbilical Cord
Allogenic stem cells:
Allogenic stem cells are those procured from matched related or unrelated donors. These may be subdivided into those of embryonic origin or non-embryonic origin such as the cells procured from another person’s umbilical cord.
How They are Processed
Minimally manipulated:
Minimally manipulated stem cells are those which are transplanted without altering their fundamental nature.
More than minimally manipulated:
More than minimally manipulated stem cells are those which are transplanted after significantly altering their fundamental nature.
What is stem cell therapy?
Recently, stem cell therapy is evolving as a new treatment for various incurable disorders such as autism. This therapy aims at replacing the damaged cells of the body using healthy cells. In autism, selective areas of the brain are damaged and do not function normally. Hence, this therapy helps in repairing and restoring the affected functions and thereby improving the quality of life of the individuals affected with autism. It helps to make these children independent and integrate them into the society.
Stem Cells Repair, regenerate and replace the damaged cells in the brain of the individual with autism.
What Do We Think?
The following is the view of Autism Connect and is meant to help parents decide:
Based on a review of the literature, along with the information available in the public domain and personal discussions with parents who have already taken stem cell therapy for their children, we believe that stem cell therapy definitely offers a potential medical solution to healing those parts of the dysfunctional brain that cause autism.
We are in agreement with the statement made in the white paper published by the International Society for Cellular Therapy with regard to two aspects
The right to seek treatment:
"Patients seeking medical treatment for cellular therapies have the following rights that must be respected by healthcare providers and all associated with their care. a. The right to seek treatment: patients and their families/partners have the right to seek treatments for their diseases. No entity should withhold this fundamental right unless there is a high probability of harm to the patients. b. The right to information: patients have the right to an accurate representation regarding the safety and efficacy record of the cell treatment. This includes probable side-effects and a truthful record of efficacy. c. The right to informed consent: patients have a right to a true informed consent process that includes all the elements described above."Distinction between legitimate medical stem cell therapy services and fraudulent services:
"The following guidelines are useful in assessing scientific rigor and for differentiating between legitimate cell therapy medical services (including clinical trials and medical innovation) and fraudulent cell therapies."Peer review and transparency: consumers of cell therapy medical innovation should evaluate evidence from peer-reviewed publications, professional society presentations and scientific recognition. They should be encouraged to seek multiple professional opinions and have all questions answered to their satisfaction.
Safety and regulatory history: patients should consider the reputation of the investigator and clinic, as well as the record of disciplinary activities against these entities.
Informed consent:patients should expect to be informed fully and accurately of the risks, benefits, costs, safety, compensation for injury, investigator conflicts of interest and alternative therapies, as a minimum."
Bearing this in mind, as a minimum, below are our recommendations to parents looking at the option of stem cell therapy for their children
(Please note that this is not a substitute for a formal medical advice and all parents are required to do their own due diligence before making this important decision.)
All parents should initially try the conventional rehabilitative treatment such as occupational therapy, speech therapy, ABA, etc. They should also take all the medications advised by the pediatric neurologists/psychiatrists/other physicians to control symptoms such as epilepsy, hyperactivity, etc. Complementary treatment such as dietary regulation, supplements, etc. may also be considered. Stem cell therapy should be considered only for those where despite all conventional rehabilitation, the child continues to remain significantly symptomatic.
Once parents have decided to consider stem cell therapy, the next important decision would be which type of stem cells to take and where to undergo the therapy. The following is our view in this connection:
We believe in safety first and therefore recommend that at this stage of evolution of stem cell therapy, it is safer to use:
Autologous stem cells
Minimally manipulated stem cells
Bone marrow derived stem cells (since these are obtained by a needle aspiration only, as compared to abdominal fat stem cells, which require a surgical procedure of laparoscopy to extract the fat from the abdomen).
We would also recommend that parents should consider only those centres that have published their safety and clinical research in scientific medical journals.
The reason for this is that when something is published in a medical journal, it is considered as peer-reviewed. This means that someone apart from the treating doctor has reviewed the safety and efficacy of the treatment and considered it worthy and accurate enough to be published in their journal. We believe that information on hospital and clinic websites online is not good enough, since there is no system of checks and balances to ensure that only authentic and accurate information is put up on the website.
On review of the medical literature through the PubMed scientific database, we have found that the following centers have published their clinical results in medical journals. These are listed in the chronological order of date of publication:
1. NeuroGen Brain and Spine Institute, Mumbai, India
Total Number Of Scientific Publications On Stem Cell Therapy in Autism: 15
Main Publication: Autologous bone marrow mononuclear cell therapy for autism - an open label proof of concept study. Stem cell international. 2013(2013), Article ID 623875, 13 pages. Alok Sharma, Nandini Gokulchandran, Hemangi Sane, Anjana Nagrajan, Amruta Paranjape, Pooja Kulkarni, Akshata Shetty, Priti Mishra, Mrudula Kali, Hema Biju, Prerna Badhe. Click here to access full text article.
The above publication, along with 14 more publications on autism from this institute, can be accessed here
2. Shenzhen Beike Biotechnology Co Ltd Shenzhen China
Total Number Of Scientific Publications On Stem Cell Therapy in Autism: 1
Yong-Tao Lv, Yun Zhang, Min Liu, Jia-na- tiQiuwaxi, Paul Ashwood, Sungho Charles Cho et al. Transplantation of human cord blood mononuclear cells and umbilical cord-derived mesenchymal stem cells in autism. Journal of Translational Medicine 2013, 11:196
The above can be accessed here
3. Emcell, Kyiv, Ukraine.
Total Number Of Scientific Publications On Stem Cell Therapy in Autism: 1
Bradstreet JJ, Sych N, Antonucci N, Klunnik M, Ivankova O, Mat Yashchuk I, M Demchuk; Siniscalco D. Efficacy of fetal stem cell transplantation in autism spectrum disorders: an open-labeled pilot study. 2014;23 Suppl1:S105-12
The above can be accessed here
4. Duke Centre for Autism and Brain Development, Duke University Medical Centre, Durham, USA
Total Number Of Scientific Publications On Stem Cell Therapy in Autism: 1
Dawson, Geraldine, Jessica M. Sun, Katherine S. Davlantis, Michael Murias, Lauren Franz, Jesse Troy, Ryan Simmons, Maura Sabatos‐DeVito, Rebecca Durham, and Joanne Kurtzberg. "Autologous cord blood infusions are safe and feasible in young children with autism spectrum disorder: Results of a single‐center phase I open‐label trial."Stem Cells Translational Medicine 6, no. 5 (2017): 1332-1339.
The above can be accessed here
Although many centers all over the world claim to get good clinical results with stem cell therapy, there is no way we can authenticate or validate those claims. Hence, our recommendation to parents is to preferably consider the centers, whose work is published.
What are the results and improvements after stem cell therapy in autism?
The outcome of stem cell therapy in autism is remarkably positive. A decrease in aggressive behavior & hyperactivity, improved eye contact & attention span, improvements in communication & social skills are observed. Improvements are also reported in the PET-CT scan of the brain as the change in metabolic activity of the brain. These changes correlate to the clinical improvements confirming the positive effect of stem cell therapy in autism. Below is the summary of the results of the papers published.
| Autologous bone marrow mononuclear cell therapy for autism an open label proof of concept study. | ||||||
|---|---|---|---|---|---|---|
 India | ||||||
| Author | ||||||
| Alok Sharma, Nandini Gokulchandran, Hemangi Sane, Anjana Nagrajan,Amruta Paranjape, Pooja Kulkarni, Akshata Shetty, Priti Mishra, Mrudula Kali, Hema Biju, Prerna Badhe. | ||||||
| Type of cells used | Source | Demonstrated Safety | Number of publications | Efficacy | ||
| Autologus | Bone Marrow | 15 |  | |||
| Transplantation of human cord blood mononuclear cells and umbilical cord-derived mesenchymal stem cells in autism | ||||||
|---|---|---|---|---|---|---|
 China | ||||||
| Author | ||||||
| Yong-Tao Lv, Yun Zhang, Min Liu, Jia-na-tiQiuwaxi, Paul Ashwood, Sungho Charles Cho, YingHuan,Ru-Cun Ge, Xing-Wang Chen, Zhao-Jing Wang, Byung-Jo Kim and Xiang Hu | ||||||
| Type of cells used | Source | Demonstrated Safety | Number of publications | Efficacy | ||
| Allogenic | Umbilical Cord | 1 |  | |||
| Efficacy of fetal stem cell transplantation in autism spectrum disorders: an open-labeled pilot study. mesenchymal stem cells in autism | ||||||
|---|---|---|---|---|---|---|
 Ukraine | ||||||
| Author | ||||||
| Bradstreet JJ, Sych N, Antonucci N, KlunnikM ,Ivankova O, Mat Yashchuk I, M Demchuk; Siniscalco D. | ||||||
| Type of cells used | Source | Demonstrated Safety | Number of publications | Efficacy | ||
| Allogenic | Aborted Fetuses | 1 |  | |||
| Autologous Cord Blood Infusions Are Safe and Feasible in Young Children with Autism Spectrum Disorder: Results of a Single-Center Phase I Open-Label Trial mesenchymal stem cells in autism | ||||||
|---|---|---|---|---|---|---|
 USA | ||||||
| Author | ||||||
| Geraldine Dawson,Jessica M. Sun,Katherine S. Davlantis,Michael Murias, Lauren Franz,Jesse Troy,Ryan Simmons, Maura Sabatos-DeVito,Rebecca Durham, Joanne Kurtzberg | ||||||
| Type of cells used | Source | Demonstrated Safety | Number of publications | Efficacy | ||
| Autologus | Umbilical Cord | 1 |  | |||
What Is Hyperbaric Oxygen Therapy(HBOT)
Hyperbaric oxygen therapy is a new form of medical treatment which is being studied extensively for autism. It is a safe, effective and a non-invasive procedure. “Hyper” means more and “Baric” means pressure, i.e. this therapy uses pressure to distribute more oxygen into body tissues such as the brain along with blood, cerebrospinal fluid, etc.
How does HBOT work in Autism
Decreased blood flow, inflammation, weak immune system, excess of free radicals are one of the few factors leading to autism.
In HBOT, at high atmospheric pressure, maximum oxygen is dissolved in the blood, so 100 % oxygen is available to the body. Thus, increasing the oxygen at cellular level results in repair of the damaged cells. forming new blood vessels, repair of the damaged cells and preventing further damage to the brain cells. This helps to improve the function of the damaged brain areas and further improve symptoms.
It regulates the immune system and reduces inflammation.
It may help in decreasing seizures.
HBOT also functions as an antibiotic as it helps to decrease the abnormal pathogens in the gut often found in children with autism and improve dysbiosis.
The body’s healing process improves.
Various studies have demonstrated use of HBOT in improving speech, cognition, memory, behavior, hyperactivity, etc in Autism.
How Is HBOT Done
In an enclosed, specially designed, pressurized chamber, the patient inhales 100% oxygen at a pressure three times greater than normal atmospheric pressure. Each session of HBOT lasts upto 45-60 minutes. Patients may require upto 40 sessions of HBOT to see the benefits.
What are the side effects of HBOT
However, it may also have some side effects such as Barotraumatic injury (in the ear, nasal sinuses, lungs and teeth), oxygen toxicity, myopia, cataract, claustrophobia, anxiety. Inhalation of high concentration of oxygen under pressure may also result in seizures. Prolonged treatment of HBOT may also lead to chest tightness and toxic pulmonary effects. The effects of HBOT are not consistent in all studies. Even though some children may benefit from HBOT, it is still not an established treatment. It is highly recommended that before deciding on the treatment you discuss the details of HBOT with the specialist doctor and know whether it will help your child.
HBOT being administered by a medical practitioner to a patient.
What is Ozone therapy
Ozone therapy is a non-invasive alternative medicine therapy, which has been used extensively for many years in several medical conditions. Ozone therapy combines a mixture of 99.5% to 95% oxygen (O2) and 0.5% to 5% ozone (O3) in varying therapeutic concentrations. Its therapeutic benefits have been scientifically proven with minimal side effects.
How does Ozone therapy work in Autism
Ozone therapy can be very effective for children with autism. In autism, there is immune dysregulation, inflammation, oxidative stress, decreased availability of antioxidants, and also presence of infections. Ozone addresses these concerns with its long-term anti-inflammatory, immunomodulatory, anti-viral, anti-fungal, and anti-bacterial properties. It helps in stimulation of internal antioxidants and thus reduces oxidative damage at cellular levels. It can assist and improve issues with medical problems, behavioral issues, the GI tract, immune system, and endocrine (hormonal) systems, and dental decay. It helps with sleep, aggression, anxiety, and speech.
How is ozone therapy done
Ozone can be administered into the ear (in-ear insufflation), rectally (Rectal insufflation) or intravenously if the child is able to tolerate it. You should first speak to your doctor and if advised, ozone therapy should be taken under medical supervision.
What are the side effects of Ozone Therapy
Ozone therapy when administered correctly does not have any major side effects.
However, when inhaled it can cause severe irritation to the eyes and respiratory passages and lungs further triggering asthma, choking, or shortness of breath.
Ozone Therapy Machine
Ozone Therapy Being administered into the ear to a Child
References
- Karima H. Minor ozonated autohemotherapy in a 2 year old boy with speech delay and cytomegalovirus infection: a case report. Ozone Therapy Global Journal. 2018 May 22;8(1):165-9.
- Siniscalco D, Luongo C (2015) Research Hypothesis in Autism: The Role of Therapeutical Ozone. Autism Open Access 5: e129.
- Bocci V. Oxygen-ozone therapy: a critical evaluation. Springer Science & Business Media; 2002 Apr 30.
- Di Paolo N, Bocci V, Gaggiotti E. Ozone therapy. The International journal of artificial organs. 2004 Mar;27(3):168-75.
- Bocci V. The Clinical Application of Ozonetherapy. OZONE. 2010 Sep 24:97–232.
- Tom Seymour - Medicalnewstoday articles 320759 May 10, 2020
What is Neurofeedback?
Neurofeedback is a computerized method based on tracking electrical activity of the brain (EEG) and giving a feedback about it. It is a non-invasive technique used to enable individuals to change their brain activity. Neurofeedback is not a new concept, it has been used since the late 1990s in children with Autism.
An EEG(An electroencephalogram is a test that detects electrical activity in your brain) of the patient is recorded using electrodes with various audio / visual stimuli on a computer screen. Based on this, a treatment plan is made by the experts for every individual to determine which brain areas need to be trained and the location on the scalp to perform the training.
Patients have EEG electrodes attached to their scalp and EEG activity is expressed in the form of sounds or pictures projected on a computer screen and fed back to them automatically through different feedback games. According to this feedback mechanism, children learn to modulate their EEG activity. By using video or sound, a desired brain activity is given a positive feedback and undesired activity is given negative feedback.
How it works in Autism?
The goal of neurofeedback is to improve behavioral or cognitive processes related to brain activity.In Autism, neurofeedback helps alter the neurophysiological profile of the patient so that it matches that of typically developing children. It works by developing new brainwave patterns and improving brain connectivity. This can subsequently help improve symptoms such as speech, behaviour, etc. These improvements help patients with autism function more effectively, improve their quality of life and make them more confident.
What are the benefits of Neurofeedback?
Improvements of neurofeedback include but are not limited to the following:
- Reduced stimming
- Reduction of emotional outbursts
- Substantial reduction and/or elimination of ritualistic behaviors.
- Improved concentration and focus.
- Increased initiation of touch and contact
- Improvement in clarity of speech patterns
- Overall improvement of social skills
- More responsive to parental and teacher instructions
- Reduced impulsivity and hyperactivity
- Increased imagination and creativity
- Ability to cope with the seemingly sudden change without feeling overwhelmed.
Mental health professionals like psychologists, counselors and family therapists who are certified neurofeedback practitioners can perform neurofeedback training. Number of sessions varies depending on the need of the patient. Neurofeedback sessions are usually given over six months to see its effectiveness. Each session may last for 20-60 minutes, alternating between training and rest.
What are the side effects?
Neurofeedback therapy is incredibly safe for individuals with autism. Some patients may experience a period of adjustment, or may be incompatible with the treatment.
Rare side effects may include:
- Low energy or fatigue
- Nausea
- Anxiety
- Depression
- Headaches
- Dizziness
- Irritability
- Cognitive impairment
- Internal vibrations
- Muscle tension
- Social anxiety
References
- Coben, B., Linden, M., & Myers, T. E. (2010). Neurofeedback for autistic spectrum disorder: A review of the literature. Applied Psychophysiology Biofeedback. 35, 83–105. DOI 10.1007/s10484-009-9117-y
- Thompson, L., Thompson, M., & Reid, A. (2010). Neurofeedback outcomes in clients with asperger’s syndrome. Applied Psychophysiology Biofeedback. 35, 63-81. DOI 10.1007/s10484-009-9120-3
- Wang, Y., et al. (2016). Relative power of specific EEG bands and their ratios during neurofeedback training in children with Autism Spectrum Disorder. Frontiers in Human Neuroscience, 9, 723.
- Jarusiewicz, B. (2002) Efficacy of Neurofeedback for Children in the Autistic Spectrum: A Pilot Study, Journal of Neurotherapy: Investigations in Neuromodulation, Neurofeedback and Applied Neuroscience, 6:4, 39-49. http://dx.doi.org/10.1300/J184v06n04_05
- Pineda J. A., et al. (2008). Positive behavioral and electrophysiological changes following neurofeedback training in children with autism. Research in Autism Spectrum Disorders, 2, 557–581. doi:10.1016/j.rasd.2007.12.003
- Thompson, M., & Thompson, L. (2003). The neurofeedback book: An introduction to basic concepts in applied psychophysiology. Wheat Ridge, CO: Association for Applied Psychophysiology and Biofeedback.
