EXOSOMES

One major aims of regenerative medicine is to replace lost tissue with new cellular material or to improve the regeneration of damaged, malfunctioning, diseases tissue and organs using stem cell transplantation. In view of this,  the discovery of Extracellular vesicles (EVs) in the twentieth century have being considered as significant factors in inflammation and immune responses, antigen presentation, immunomodulation, coagulation, tissue regeneration, organ repair, cell-cell communication, senescence, proliferation and differentiation in the body [1].  Extracellular vesicles are believed to be involved in many biological processes and they can be modified to contain specific proteins, genetic lipids, and genetic materials including messenger RNA (mRNA), microRNA (mRNA), and other small non-coding RNAs, and genomic DNA (gDNA) from their progenitor cell.
Extracellular vesicles are classified into two groups which include; exosomes and ectosomes [2]. Exosomes are characterized with cup-shaped morphology, appearred as flattened spheres with diameters ranging from 30 to 150 nm. Similarly, exosomes have a characteristic lipid bilayer which has an average thickness of ~5 nm. [3]. Thus, the lipid components of exosomes include ceramide (sometimes used to differentiate exosomes from lysosomes), cholesterol, sphingolipids, and phosphoglycerides with long and saturated fatty-acyl chains. The exosome is formed or derived from a multivesicular body (MVB) when the MVB fuses with the plasma membrane and is released into the extracellular environment.                                 
                                    
 Diagrammatic representation of a medium size Exosome.
Exosomes contain many types of biomolecule, including proteins, carbohydrates, lipids and nucleic acids which vary depending on the EV’s origin, its physiological and pathological state, and even the precise cellular release site. Thus, the protein composition within can also mark the existence of disease pathologies such as inflammatory diseases; however, exosomes also contain a number of common proteins as well as those that participate in vesicle formation and trafficking. Furthernore, exosome plays a role in intercellular communication by carrying proteins and RNAs between neighboring cells or even to distant organs, they also bind to cell membranes through receptor– ligand interaction and mediate antigen presentation, cancer progression etc.
Various techniques have being developed for the isolation of exosomes which includes; ultracentrifugation-based isolation techniques, size-based techniques, precipitation techniques, immune-affinity capture-based techniques, and some novel combination techniques [4]. Exosomes primarily exist in pellets after centrifugation 100000–200000×g  and the use of Ultracentrifugation and ultrafiltration can be used to obtain purified exosomes in the laboratory, but this technology is difficult to apply on a large scale [5].
Exosomes can be stored at 4°C for up to 1 week for short-term while it can be stored at  -80°C for long-term by suspending it in phosphate buffered saline.
More importantly, growing evidence has also suggested that exosomes play a key role in facilitating tumorigenesis by regulating angiogenesis, immunity, and metastasis. Circulating exosomes in body fluids and blood in particular are potentially non-invasive or minimally invasive biomarkers for early diagnosis and prognosis of various types of cancer.[6] As the first step towards improving human health, exosomes have to be reliably and efficiently isolated from complex biological matrices like blood, urine, and cerebrospinal fluid since they are currently tested as next-generation biomarkers in those body fluids.
In conclusion, it is advantageous to use exosomes for cell based treatments because the use of exosomes can avoid problems associated with the transfer of cells, which may already have damaged or mutated DNA [7]. Also, exosomes are small and can easily circulate through capillaries, whereas the cells used in other cell-based therapies, such as MSCs, are too large to go through capillaries, and thus cannot get beyond first pass capillary beds, such as the lungs.
The level of MSCs in cell-based therapies may quickly diminish after transplant while, exosomes can achieve a higher “dose” than the transplanted MSCs [8]. Similarly,  exosomes can also be utilized to tackle toxicity and immunogenicity problems resulting from such biomaterial treatments as nanoparticles [9].
CLINICAL APPLICATION
Ø    Immuno-modulatory and anti-inflammatory properties of Exosomes could be the potential biological mechanisms for clinical treatment to promote bone regeneration. [10]
Ø  Adipose-derived stem cell-derived exosomes promote fracture healing in animals by binding to polylactic acid-glycolic acid scaffolds.
Ø  Exosome can be used for the treatment of chronic kidney disease, type 1 diabetes mellitus, and skin damage [11].
Ø  MSCs-derived exosomes have shown therapeutical benefits in stroke and intravenous administration of MSCs-derived exosomes induced an increase of neurogenesis, neurite remodeling, and angiogenesis. [12]
Ø  Administration of MSCs-derived exosomes’ has being observed in a traumatic brain injury model by showing an inflammation reduction and good outcomes.[13]
Ø  The injection of MSCs-derived exosomes has also been shown to be a possible treatment for spinal cord injury (SCI), by reducing inflammation and by promoting neuro-regeneration in rats after injury [14].
Ø  Exosomes can be used as a delivery system of therapeutic signals or drugs due to their low immunogenicity, ability to cross the blood-brain barrier (BBB), and long half-life in circulation.
 
 

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MESENCHYMAL STEM CELLS

Over the last decade, cellular therapy has developed quickly at the level of in vitro and in vivo preclinical research and in clinical trials. Thus, one of the types of adult stem cells that have provided a great amount of interest in the field of regenerative medicine due to their unique biological properties is Mesenchymal stem cells (MSCs).
 Mesenchymal stem cells (MSCs) are known to be multipotent stromal cells that can differentiate into a variety of cell types which include osteoblasts (bone cells), chondrocytes (cartilage cells), myocytes (muscle cells) and adipocytes (fat cells which give rise to marrow adipose tissue). Furthermore, MSCs are responsible for tissue repair, growth, wound healing and cell substitution resulting from physiological or pathological causes; they have various therapeutic applications such as in the treatment of central nervous system afflictions like spinal cord lesions (1). Similarly, they are characterized by an extensive capacity for self-renewal, proliferation, potential to differentiate into multiple lineages and their immune-modulatory role on various cells.
Mesenchymal stem cells have the ability to expand in many folds in culture while retaining their growth and multilineage potential. Also, they can be identified by the expression of many molecules including CD105 (SH2) CD73 and CD34, CD45.  Thus, these properties of MSCs make these cells potentially ideal candidates for tissue technology.
In addition, it has been discovered that MSCs, when transplanted systemically, have the ability to transport to sites of physical harm or damage in animals, suggesting that MSCs have migratory capacity. This migration property of MSCs is important in regenerative medicine, where various injection routes are utilized depending on the damaged tissue or organ.
The first source of Mesenchymal stem cells was in the bone marrow and considered to be the gold standard for clinical research, although various other sources have being discovered which include: Adipose tissue, Dental pulp, Mobilised Peripheral blood, Amniotic fluid, Joint synovium, synovial fluid, Endosteum, Periosteum, Menstrual blood and birth-derived tissues.
Cohnheim (German Biologist) hypothesized in the late nineteenth century that fibroblastic cells derived from bone marrow were involved in wound healing throughout the body, while in 1970, Alexander Friedenstein described a population of plastic-adherent cells that emerged from long-term cultures of bone marrow and other blood-forming organs, and he showed to have colony forming capacity and osteogenic differentiation characteristics in vitro as well as in vivo upon re-transplantation.
Arnold Caplan (1991),  coined the term “mesenchymal stem cell and stated that the cells as multipotent mesenchymal cell populations which can differentiate into several tissue types, and demonstrated roles for MSCs in the regeneration of bone, cartilage or ligaments in animal and clinical studies. However, the first clinical trials of MSCs were completed in 1995 when a group of 15 patients were injected with cultured MSCs to test the safety of the treatment.
According to International Society for Cellular Therapy, the proposed minimum criteria to define MSCs include the following:
 (a) The cells should exhibits plastic adherence
(b) The cell should possess specific set of cell surface markers, i.e. cluster of differentiation (CD) 73, D90, CD105 and lack expression of CD14, CD34, CD45 and human leucocyte antigen-DR (HLA-DR).
(c) The cells should have the ability to differentiate in vitro into adipocyte, chondrocyte and osteoblast.
Thus, these characteristics are valid for all MSCs, although few differences exist in MSCs isolated from various tissue origins.
Mesenchymal stem/stromal cells (MSCs) can be isolated from neonatal tissues, most of which are discarded after birth, including placental tissues, fetal membranes, umbilical cord, and amniotic fluid. Placenta is an ideal starting material for the large-scale manufacture of multiple cell doses of allogeneic MSC. The placenta is a fetomaternal organ from which either fetal or maternal tissue can be isolated.
MSC derived from placenta have long-term proliferation and immunomodulatory capacity, superior to bone marrow-derived MSC. The placenta is a fetomaternal organ consisting of both fetal and maternal tissue, and thus MSC of fetal or maternal origin can be, theoretically isolated.  Thus, neonatal tissues are easily available and they have biological advantages in comparison to adult sources that make them a useful source for stem cells including MSCs. They appear to be more primitive and have greater multipotentiality than their adult counterparts.
 Clinical Application
Ø  MSCs have been widely used to treat immune-based disorders, such as Crohn’s disease, rheumatoid arthritis, diabetes, and multiple sclerosis.
Ø  MSCs have been widely used as a treatment for numerous orthopedic diseases, including bone defects, osteoarthritis (OA), femoral head necrosis, degenerative disc, spinal cord injury, knee varus, osteogenesis imperfecta, and other systemic bone diseases.
Ø  MSCs are promising cell source for treatment of autoimmune, degenerative and inflammatory diseases due to the homing ability, multilineage potential, secretion of anti-inflammatory molecules and immunoregulatory effects.
Ø  MSCs play a key role in the maintenance of bone marrow homeostasis and regulate the maturation of both hematopoietic and non-hematopoietic cells.
Ø  MSCs have been shown to be powerful tools in gene therapies, and can be effectively transduced with viral vectors containing a therapeutic gene, as well as with cDNA for specific proteins, expression of which is desired in a patient.
Ø  It has been proved that MSCs can differentiate into insulin producing cells and have the capacity to regulate the immunomodulatory effects 
REFERENCES

  1.     Wei X, Yang X, Han ZP, Qu FF, Shao L, Shi YF. Mesenchymal stem cells: a new trend for cell therapy.  Acta Pharmacol Sin. 2013 Jun; 34(6):747-54
  1.     Friedenstein AJ, Piatetzky II S, Petrakova KV. Osteogenesis in transplants of bone marrow cells. J Embryol Exp Morphol. 1966;16:381–90
  1.     Friedenstein AJ, Chailakhyan RK, Latsinik NV, Panasyuk AF, Keiliss-Borok IV. Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues. Cloning in vitro and retransplantation in vivo. Transplantation. 1974;17:331–40.
  1.     Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284:143–7.
  1.     Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell Biochem. 2006;98:1076–84.
  1.     Wang S, Qu X, Zhao RC. Clinical applications of mesenchymal stem cells. Journal ofHematology & Oncology. Apr 30, 2012;5:19.
  2. Dominici, M., Le Blanc, K., Mueller, I., Slaper-Cortenbach, I., Marini, F., Krause, D., Deans, R., Keating, A., Prockop, D. and Horwitz, E. (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular. Therapy position statement. Cytotherapy 8, 315–317
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What Are The Best Options For Managing Chronic Pain?

Chronic pain. Roughly translated as a condition of persistent misery for people.  It is a serious health condition that has both physical and psychological suffering and is often associated with a specific ailment like arthritis, migraine, frozen limb, etc. People who suffer from chronic pain perceive themselves to be in a state of constant agony and distress, which can affect their ability to lead a ‘normal’ life, from being able to go to work every day to social interaction.
There are several treatment options that people resort to for managing persistent pain conditions. In this article, we talk about those treatment options with the stem cell regeneration being the most current and promising one. Also, we will discuss the potential benefits and pros and cons of regenerative medicine.

What is chronic pain and how is it caused?

During ‘PAINWeek2017’ in Las Vegas, Dr. Jay Joshi, MD, explained the connection between inflammation and pain. He states that inflammation is triggered by various chemical and physical stimuli, and is a normal phenomenon of the body to protect the injured area and speed up the healing process. When inflammation exceeds its normal extent, it conversely delays the healing process and forms this cycle of non-resolving inflammation that leads to chronic pain.
Chronic pain is a multifactorial condition. It can be caused by medical harm, injury or nerve damage. However, it can also be caused by environmental factors, for example, back pain due to incorrect posture, or physiological factors such as aging, weak bones.
Common conditions that are related to chronic pain are:

  1. Osteoarthritis: the degeneration of cartilage in the joint and the corresponding bones, leading to pain and stiffness mainly in thumb, knee and hip joints.
  2. Migraine: a half-sided recurrent headache that gives a throbbing sensation and is accompanied by blurred vision and nausea.
  3. Multiple Sclerosis: a chronic, progressive condition that involves nerve cell sheath damage in the spinal cord and brain. Its symptoms include severe fatigue, speech disturbances, blurred vision and numbness.
  4. Neuropathy: a condition that involves damage to the peripheral nerves causing weakness, pain and numbness, particularly in the hands and feet.
  5. Fibromyalgia: a soft tissue disorder that involves widespread musculoskeletal pain also characterized by fatigue, sleep disturbance and mood swings.

According to a 2016 analysis by the National Health Interview Survey, approximately 50 million Americans suffer from chronic pain. It is considered to be one of the most common conditions that medical treatment is sought out for. Some of the repercussions of chronic pain that agonize people are: 

  • Depression and mood swings
  • Poor performance
  • Poor social life
  • Restricted mobility
  • Anxiety
  • Poor self-perception about life
  • Dependence on opioids

Although it is necessary to diagnose and treat the underlying cause of pain, doctors deal with pain as a separate entity and provide symptomatic treatments to save patients from the continuous discomfort it brings.

Management of Chronic Pain

Some of the common management strategies adopted by doctors are: 
Analgesics
There are several over the counter pain killers available that are widely used by patients with chronic pain. These include paracetamol, acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, ibuprofen, naproxen, etc.
Although analgesics are considered safe, long term usage can produce a number of side effects. It can lead to liver damage and is specifically dangerous for patients with liver cirrhosis. Likewise, NSAIDs are known to affect the kidneys and increase the risk of a heart attack.
Anticonvulsants
Drugs that are originally used to treat epilepsy can also be an effective management strategy against chronic pain. For example, the second-generation anticonvulsants Gabapentin and Lyrica are approved by FDA for the treatment of pain.  First-generation anticonvulsants such as carbamazepine and phenytoin are also considered effective. However, these first-generation drugs have more side effects when compared to second-generation drugs. They can cause side effects like ataxia, liver damage, sedation, etc.
Antidepressants
Doctors also prescribe antidepressants for the treatment of pain. These comprise of tricyclics like amitriptyline, imipramine or doxepin. These drugs can be given to patients with or without depression as it has distinct effects of pain relief and mood elevation.
Similarly, pain in fibromyalgia and diabetic nerve pain are treated with other types of antidepressants – serotonin and norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine and duloxetine. These are equally effective as tricyclics but have comparatively milder side effects.
Opioids
Opioids such as codeine, morphine, oxycodone, etc. are very effective against severe chronic pain conditions. However, these drugs are not available over the counter and not provided by the pharmacist without prescription because of their risk of addiction.
Nonetheless, experts state that if the dose is vigilantly managed, their potential benefits can outweigh the risks. That is why doctors carefully observe patients prescribed with opioids for chronic pain to avoid any untoward dependence.
Alternative medicine
If traditional medicine hasn’t worked, many people often resort to other naturally occurring remedies for its cure. Alternative medicine varies from herbal remedies and therapies that are naturally available in plants that have curative properties. Cannabinoids, Akuamma and Kratom plants are a few examples with such characteristics that are currently trending.

Could Stem Cell Regeneration (SCR) be the answer?

As the human central nervous system matures and becomes more complex, the regenerative ability of the body further reduces. Regenerative medicine caters for this by focusing on the 3 Rs; Replacement, Repair, and Restoration of tissues and their function. This can be directed for the treatment of non-resolving inflammation by generating ex vitro cells, tissues or organs which can then be transplanted into the body.
Stem cell therapy is a unique model of treatment that replaces injured or lost cells, which can help 1.5 billion people that are experiencing chronic pain worldwide, with 23-26% of the people suffering from lower backache alone. According to Dr. Jay in ‘PAINWeek2017’, there are two types of stem cell regenerative therapy: Autologous and Non-Autologous.
In autologous SCR, mesenchymal stem cells (MSCs) are derived from adipose tissue of the patient and transplanted back into the injured area, where they potentially differentiate into the respective cells. For the other type, the MSCs are derived from embryonic tissues.
Research published in Pain Physician Journal in 2017 shows that MSC therapy is a great alternative because they are readily available. In addition, their homing potential is also considered a pro and they can be grown using standard culture techniques. It has also shown that autologous SCR is potentially safe for both humans and animals.
There has been a reported reduction from pre to post-operative pain with the use of SCR. However, various complications have been acknowledged in studies. Firstly, there’s a risk of tumor formation at the site of transplantation. Secondly, there have been instances of undesired bone formation. Furthermore, there is also a risk of abnormal immune reactions to occur.
The effective results of cell-based therapy are promising, with evident results in the treatment of chronic pain conditions in osteoarthritis, degenerative disc disease as well as neuropathic pain. However, there is still a need for advanced clinical research to deepen the understanding of the mode of action of MSCs and their potential outcomes inside the human body.

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Which are the best options For Treating Common Sports Injuries?

As physicians, we are constantly dealing with sports injuries. While they are typically not seen as life-threatening with high chances of recovery, they could potentially cause further problems down the line for the patient. Sports injuries can also take months to heal and getting patients back on their feet can take a lot of time, effort and money, which can be frustrating for patients who want to get back to playing football every weekend or for those who have a skiing holiday booked in the next month. 
Recently, there has been a massive surge in the use of stem cells as an alternative treatment to common sports injuries. This article aims to outline the benefits and risks attached to using stem cells and how this alternative treatment may help patients who are suffering from common sports injuries. 

What Are The Most Common Sports Injuries?

We are constantly treating sports injuries on a regular basis. Some of the most common sports injuries doctors typically deal with are:
Ankle Sprain
An ankle sprain occurs when the ligaments in the ankle are stretched and eventually torn due to twisting or falling onto the foot. Ankle sprains are common among athletes and sports enthusiasts, however, if left untreated, the ankle can weaken, making it more vulnerable to further damage. This leads to long term problems such as chronic ankle pain, arthritis, and ongoing instability. 
A sprained ankle can be easily diagnosed when we see displays of swelling, bruising, stiffness and pain when we attempt to touch or move the ankle. 
Groin Pull
A groin pull is basically a groin strain. Strains occur when the muscles are overstretched, moving in directions that are not normal for them or pulled too forcefully or suddenly. This leaves them torn and damaged and results in tenderness and bruising in the groin and inner thigh area. This injury is common in athletes that play sports which require a lot of quick side-to-side movements. 
A groin pull can be easily diagnosed after a thorough physical examination of the symptoms and possible tests such as x-rays and MRI’s.
Hamstring Strain
A hamstring strain occurs when the three muscles in the back of the thigh are overstretched from movements such as hurdling and kicking the leg out sharply. As these muscles are naturally tight and susceptible to sprains, it can take from six to twelve months to heal and are vulnerable to recurring injuries. Poor or lack of stretching are the likely causes of a pulled hamstring. 
Shin Splints 
Shin Splints is an inflammation of the muscles in the lower leg when they are overworked and stressed. Shin splints are often found in athletes that engage in sports that require a lot of running, dodging or quick stops and starts.
Knee injury: ACL tear
An ACL knee injury is a tear or sprain of the ligament that holds the leg bone to the knee. Sudden stops or changes in direction can tear the ACL and make that dreaded “pop” sound. Almost immediately, the knee will swell, feel unstable and be too painful to bear weight. This injury is common in athletes that engage in sports such as soccer, basketball, and downhill skiing. 
ACL tears are commonly seen as a severe sports injury and can be traditionally treated with rehabilitation programs and surgery to strengthen or completely replace the torn ligament. 
Knee injury: Patellofemoral Syndrome 
Patellofemoral Syndrome occurs when repetitive movements of the kneecap (patella) are made against the thigh bone (femur) which damages the tissue. This knee pain is common among young adults and can be caused by a number of factors such as weakness in the thigh or buttock muscles, tight hamstrings, short ligaments around the kneecap or alignment problems through the feet. 
Tennis Elbow (epicondylitis)
Tennis Elbow is common for athletes that play sports such as tennis or golf that require the player to ‘grip’ tightly and repetitively for an extended amount of time. This results in the ligaments of the forearm becoming strained and inflamed, making it painful to make wrist or hand motions. 

What Are The Traditional Treatment Options & Management Strategies For Sports Injuries?

Traditional treatment methods and strategies for treating mild sports injuries such as sprains and strains can be done at home. Traditional advice given by doctors can include taking rest, applying ice to reduce the swelling and dressing the injury with compression bandages to support and assist healing. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen may also be prescribed to help reduce swelling and to relieve pain. 
Moderate severity injuries may be traditionally treated with immobilization strategies such as the use of crutches or a cast brace to assist the ankle to heal for the first few weeks. This may be followed with rehabilitation exercises to strengthen the ankle and prevent stiffness and future problems.
Severe sports injuries such as knee injuries are traditionally treated with surgery or rehabilitation programs to replace or restore the torn ligaments or muscles. This also goes for those patients who experience persistent problems after months of nonsurgical treatment. 
Whatever the severity level of the sports injury, the healing process can take up to several months before the muscle restores to its natural condition. Injuries can also leave muscles and ligaments permanently weakened and susceptible to further injury. 

Is Stem Cell Therapy An Option For Treating Sports Injuries? 

The use of stem cells to treat sports injuries are becoming more popular due to its ability to grow new blood vessels that facilitate faster and better healing, decrease or prevent inflammation and release proteins (cytokines) that can slow down tissue degeneration and reduce pain. Sports injuries that include damage to tendons, ligaments, muscles, and cartilage are reported to be seeing the best results from stem cell therapy. 
Dr. Bill Johnson, MD of Innovations Medical sees stem cell therapy as a revolutionary alternative to painful surgery and long recovery and states that, 
“Patients who undergo stem cell therapy for their sports injury report a reduction in their painful symptoms and increase range of motion and increased mobility. Stem cell therapy helps to quickly reduce joint inflammation, and many patients see improvements in 1 to 2 days. Anti-inflammatory results of the procedure can last for 2 to 3 months and many patients see a gradual improvement in their condition over time.”
Even celebrity athletes such as Peyton Manning and Ryan Tannehill have used stem cell treatment in conjunction with traditional treatments with success. Stem cells are placed directly into the joint via surgical application or injection to aid quicker healing and promote the growth of cells needed to restore strength and flexibility in muscles and ligaments. 
However, using stem cells as an alternative method to treat sports injuries is still a controversial subject and is very much still debated among medical professionals. Research is still undergoing to show whether or not stem cell therapy is the best solution. Critics of this therapy argue the fact that stem cell therapy doesn’t work any better than a placebo and that there is no clear evidence that this type of therapy is safe. Unwanted side effects can include swelling and pain and if stem cells are used from other sources or manipulated in any way, this can result in a higher risk of developing tumors.

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How To Effectively Treat Amyotrophic Lateral Sclerosis (ALS)

Although a rare neurologic condition, Amyotrophic Lateral Sclerosis (ALS) is the most common type of Motor Neuron Disease (MND),  a condition that affects the voluntary muscles. This is a progressive disorder that leads to muscle weakness and depletion due to nerve dysfunction.
ALS is also called Lou Gehrig’s disease, named after the football player who had this condition. The literal meaning of Amyotrophic is ‘no muscle nourishment’ which becomes the cause of muscle atrophy. ‘Lateral’ refers to the group of nerves in the spinal cord that sends signals to the muscles. It is these nerves that degenerate, leading to sclerosis in this region. In later stages, this affects the nerves that control breathing and hence can be fatal.
The initial symptoms of ALS include stiffness and muscle weakness, which gradually involves all the muscles under voluntary control. The affected regions and progressive pattern vary from one person to another. Some having difficulty holding a pen or a cup while others finding difficulty speaking, chewing or even talking. Thus, ALS is an ailment that affects daily life and makes simple tasks painful and troublesome.
According to the Center for Disease Control and Prevention (CDC), 14,500 to 15,000 people had ALS in the United States in 2016,  with approximately 5000 people having a confirmed diagnosis for the condition annually. Although the average survival rate is three to five years, patients can live for ten years or more.

Are there different types of ALS?

Amyotrophic Lateral Sclerosis has two types:
Sporadic ALS: this is the most common one and affects 95% of sufferers. This type occurs without a clear cause.
Familial ALS (FALS): This type occurs in 5-10% of sufferers. This type of ALS is genetic and runs in families. This occurs due to abnormal changes to a gene that is then passed in generations. 

What are the symptoms of ALS?

Early signs and symptoms might be unnoticeable and become perceptible after some time. Most clinical signs are evident of upper motor neuron and lower motor neuron lesion. The limb onset ALS (70%) involves initial symptoms in the limbs while the bulbar onset ALS (25%) is characterized by speech and swallowing problems. This is followed by weakness in the limbs later. The remaining 5% of the patients have respiratory involvement in the early period. [5]
Most common symptoms include:

  • Muscle weakness in the limbs (distal or proximal)
  • Asymmetric progressive muscle wasting
  • Difficulty in motor activities like walking, talking, chewing
  • Weakness in arms, legs, hands, and feet
  • Muscle cramps and twitching
  • Slurred speech
  • Fatigue
  • Emotional liability (episodes of uncontrolled laughing and crying)
  • Difficulty in maintaining posture and gait
  • Difficulty in breathing and swallowing

With the progression of the disease, symptoms may spread to all parts of the body. In some patients, frontotemporal dementia may occur resulting in poor memory and decision-making abilities.

What Causes ALS?

The exact cause of ALS has not been known by scientists to date. However, research is being carried out to understand what causes ALS. There are several different factors such as: 
Genetic changes
Studies have shown that 5 to 10% of cases of ALS are caused by genetic mutations. For example, changes to the gene that makes SOD1 protein causes damage to motor neurons. 
Environmental factors
No major association has been established between environmental factors like toxins, viruses, diet or physical trauma and the risk of development of ALS. However, there is ongoing research on the subject. Studies have shown that some athletes are at a higher risk of acquiring ALS due to vigorous physical activity. 
Chemical disturbance
Glutamate is the neurotransmitter that is in control of signals to and from the brain. Accumulation of this neurotransmitter within the spaces surrounding the nerves damages them. 
Research has also shown mitochondrial structural and functional abnormalities, as well as defects in axonal structure and transport, could be the causative agents for ALS. 

How Do We Diagnosis ALS?

When it comes to diagnosis, there are no specific tests that can provide a definitive diagnosis for ALS. However, doctors conduct a series of tests to rule other similar diseases. A full medical history check and a neurologic examination are undertaken at regular intervals to assess the progressive worsening of symptoms. 
Running the following Image testing diagnostic tests can help reach a diagnosis:

  • Electromyography (EMG) – EMG records the electrical activity of the muscle fibers.
  • Nerve Conduction Study (NCS) – NCS assesses the electrical activity of the nerves and muscles.
  • Magnetic Resonance Imaging (MRI) – MRI rules out other possible conditions such as a tumor or cyst in the spinal cord, cervical spondylosis, or a hernia in the neck that could be causing the nerve compression.

Laboratory tests such as blood screening and urine tests can also be carried out so that other diseases can be eliminated. 

What Are The Treatment Options & Management Strategies For ALS?

ALS is managed through a multidisciplinary approach.
Unfortunately, there is no definitive cure for the disease at this time. Management of ALS is done through symptomatic treatment to ease the condition of the patients and prevent unnecessary complications:
Support – Physicians, psychologists, speech therapists, nutritionists, and home care assistance all play a vital role in making life easier for patients with ALS.
Medication – Riluzole (Rilutek) and Edaravone (Radicava) are the drugs approved by the U.S Food and Drug Administration (FDA) for treating ALS. Riluzole is believed to reduce glutamate levels thereby, decreasing damage to the motor neurons. Edaravone acts an antioxidant and is believed to expel free radicals and reduce the oxidative stress in the motor neurons.
Lifestyle Habits – Physiotherapists can recommend exercise and physical activity like walking, swimming, and bicycling that may improve muscle strength and help elevate mood without overstressing the muscles.
Speech Therapy – therapists can help patients with ALS to employ strategies to speak clearly. They may also recommend computerized aids such as speech synthesizers and eye-tracking technology to help people learn ways for responding by nonverbal means.
Diet – Nutritionists may formulate a diet plan for patients, which consists of food that is easy to swallow and provides enough nourishment and calories for the patients to maintain adequate energy levels and to prevent excessive weight loss
Breathing Support – Patients with ALS may suffer from shortness of breath and difficulty breathing during physical activity or while lying down. If this is the case, doctors can recommend Non-Invasive Ventilation (NIV) that provides breathing support through the nose or mouth. NIV improves quality of life and increases the number of years of survival for patients.

Is Stem Cell Therapy An Option?

As previously mentioned, there is no curable treatment for ALS available. However, scientists are researching Stem Cell Therapy as the new favorable approach in the treatment of neurologic disorders.
There is a rising interest in Stem Cell Therapy as a promising remedy for curing ALS. Mesenchymal stem cells are particularly believed to be the most suitable ones due to their availability, absence of ethical issues and positive results in various experiments.
Studies and clinical trials have begun to apprehend the benefits of MSC transplantation. They demonstrate that MSCs lead to a partial recovery of motor neurons and a delay in disease progression. Also, there has been no evidence of a major adverse effect after MSC transplantation. 
When testing this newfound research on animals, the lifespan of the subjected animal has increased with MSC transplantation. These positive results have encouraged the administration of MSC in ALS patients. 
However, despite the safe outcomes of MSC transplantation in humans, results show that there is only a partial improvement in ALS sufferers with only a few cases that showed a delay in disease progression. Hence, there is a need for further studies and trials on a higher number of human subjects for a better understanding of MSC effects so that more significant conclusions can be reached.

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Which Works Better, Viscosupplementation, or Platelet Rich Plasma?

One of the treatments that the FDA approved for knee arthritis is a Hyalronic Acid (HA) injection, sometimes also known as  Viscosupplementation. It has been incredibly successful for knee arthritis. In fact, so successful that many physicians are starting to use it on other parts of the body, like the hip and shoulder, which the FDA does not approve of.
HA, when injected, works like the fluid that naturally surrounds your joints. This fluid can be like a lubricant for your joints, and absorb shock, allowing bones that otherwise cause arthritis pain cause much less. Over time, it is even absorbed into the joint, which can cause the body to create a more stable cartilage all on its own.
The evidence for this treatment is astounding, with a systematic review of 76 trials, all of which were randomized controller trials. The review noted that HA, when injected, can benefit function, reduce pain, and can be a reliable and effective treatment for knee osteoarthritis.

On the other hand, there is PRP therapy. Platelet Rich Plasma, or PRP, which is a type of blood that has 6 to 10 times more platelets than what is normally found in blood. They even contain many growth factors, such as Epidermal Growth Factor, Connective Tissue Growth Factor, and many more. These can help heal injured parts of the body by using the bodies natural healing tools.
However, PRP is not regulated by the FDA, and devices that are used to make PRP require said approval. Aside from this, multiple studies shoe that PRP can be very effective in the treatment of tendon injuries, as well as for osteoarthritis. This treatment can even help in the reduction of pain. There are even more studies being conducted on whether it can help other things, such as hair regrowth, cardiac muscle repair, and even dermatologic rejuvenation.
So should you use HA injections, or PRP?
In many studies, PRP has bee demonstrated to work just as well, if not better than HA. HA is also only FDA approved for the knee, meaning that it is not approved or covered for the use in any other joint. Also, the risk of infection and rejection is far less while using PRP, as it is a substance that comes from your own body, and contains white blood cells, which can help fight infection.
PRP also saves money in the long run, as using HA in a joint other than the knee is not FDA approved or covered by insurance. As a result, it can cost your patient 1500$ or more. This can even be on top of various other charges, such as doctors visits, and even the injection itself. PRP, on the other hand, only costs from 800 to 1200$ out of pocket.
So PRP has been demonstrated to be just as effective, if not better, than HA injections when it comes to arthritis pain. It does not pose a risk for infection or and auto-immune reaction either, and is even far cheaper than HA. So picking which one to use should be a no-brainer.

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How Regenerative Microneedling Can Help Rejuvenate Skin

One of the main things that causes many people cosmetic distress and low self esteem is acne scarring. Most of us have some kind of experience when it comes down to scarring, but the most embarrassing scars are the ones that are out in the open. Such as on our faces. So what can Platelet Rich Plasma do for this?
Well, both the Department of Dermatology, Venereology, and Leprosy, as well as the National Institutes of Medical Sciences have indicated that it can be used as a viable treatment for eliminating scars. One study, done by the Department of Dermatology, Venereology, and Leprosy, sought to evaluate just how effective and safe PRP therapy can be, especially when combined with microneedling. Microneedling has been a common treatment on its own for acne scars, using distilled water, for a long time.
The way that Microneedling works is that it is used to initiate collagen synthesis on the face, thus allowing the skin to heal itself. What it does is cause micro injuries to the skin of the face using small needles. However, since the needles are so small and fine, that it does not cause any serious injury. The initiation transmits electrical signals, which calls on the body to begin a healing process, by causing small inflammation and bringing growth factors to the area.
This healing process causes new blood cells to form, and thus helps to remove the scarring over time. General treatment times are known to take from just a couple of weeks up to a year in many cases. 50 patients were involved in this study, all aged 17-32, and all suffering from acne scars.
On one side of the face, they used regular distilled water combined with the microneedling procedure, and on the right they used a topical solution of PRP. After 3 treatments giving withing the time span of a 3 months, each treatment being 1 month apart, the results that used PRP was much more likely to show improvement over the distilled water group. This would be 62.2% improvement vs 45.8% respectively. This showed that PRP can have great success in managing acne scars, and helping to make them go away.
This shows that when it comes to PRP therapy, the science again shows that there is a good and significant use for it. So what is stopping you from implementing this therapy for your patients?

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How can PRP treat Tennis Elbow?

Despite what the name may imply, not all people who suffer from Tennis Elbow even play tennis. In fact, most of them aren’t. Many of them can be painters, butchers, plumbers, carpenters, and even much any career which can overuse the muscles in the forearm. This can cause the tendons elbow to become painful and inflamed.
The most common treatment for Tennis Elbow after the injury has taken place is rest, anti-inflammatory medicines, and generally physical therapy if it is needed. However, this is more of a temporary fix than a longstanding one. In many cases, if untreated, the pain will worsen, and many need things such as braces for their arm, injects of steroids, and shock wave therapy. Sometimes, although not often, they might even need surgery.
Most insurance companies are able to cover this surgery, as it is deemed medically necessary. However, it does not always end up with the best results. On occasion, surgery may even leave you in more pain than you were in before, potentially causing the need for more surgeries.
So as an alternative for surgery, perhaps try PRP, or Plasma Rich Platelet Therapy? This is a pretty simple procedure that utilizes the platelets and cells in your own body to heal your arm from the inside out. We just take out a bit of your blood, put it in a centrifuge, and extract the PRP to use on your injury. After awhile, it become good as new, without any need for surgery. It also does not need any anti-inflammatory medications, which can lower the side effects that you will see from medications and multiple surgeries.
So try it out if you would like a more holistic way of healing yourself.
 

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What’s all the fuss about Regenerative Medicine?

In popular media, the term Regenerative Medicine, or Stem Cell Therapy, are becoming buzz words. This is because the field of medicine and healthcare is expanding and advancing every day, and many new treatments for otherwise common ailments are being discovered. These conditions range from burns, joint pain, strain, and pretty much every other common ailment out there
Many patients have given up hope with trying to find traditional medicines that work. This is why many people are flocking to try Regenerative Medicine. This is also something that many people who are into holistic healing are trying, as it is simply the body working to heal itself.
Regenerative Medicine works as it takes a sample of your own blood, bone marrow, and other tissues, and then it goes through a process in which to take out a certain material known as Platelet-Rich Plasma. This PRP is then applied to the infected area, so that your body’s own platelets can work to heal your body back to full health, without having to worry about any invasive surgeries.
A good question to ask is why our body does this do this itself. Well, this is because research has shown that by isolating them, they activate, and as a result when injected back into the body start to work harder to fix the issues, such as in a joint, or helping to relieve pain. Many patients who try it say they have gotten good results from the treatment.

Many doctors predict that this therapy will help physicians provide a more non-intrusive treatment that has fewer side effects, and can be big within the coming years. Many compare it to the invention of penicillin with how important it is. It is even growing in popularity with many physicians using training courses to help their patients, leaving many of them happier and healthier.
 

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Platelet-Rich Plasma Vs Stem Cell Therapy: Who’s Bad?

The entire field of orthopedics is looking for new regenerative technology that can save more patients more safely. Currently there are two contenders: Platelet-Rich Plasma and Stem Cell.
While PRP is the safest of the two, it’s really hard to dismiss the remarkable capabilities of stem cell therapy. In fact, I believe it’s the future of regenerative medicine. But not at the level it’s playing right now. Which is a totally different discussion we’ll save for another day.
The thing is… there are potential harm with stem cells. And unlike PRP, stem cell’s constituents are man-made, so things can go wrong. We’ll discuss the potential dark side of this therapy later in this article. However, I feel it’s important to highlight how good a treatment stem cell therapy is.
Quick Overview: Stem Cell Vs Platelet-Rich Plasma
Platelet-Rich Plasma is like water and nutrients that help restore (and sometimes accelerate) your body’s EXISTING healing mechanism. If your body is stuck with its healing, PRP can help. It releases growth factors and cytokines to kick start the healing. Stem cells on the other hand is not used to enhance healing, but to create new solutions to healing challenges. So it’s more for tissues that are totally lost.
Stem Cell Vs Platelet-Rich Plasma
With me? Before we proceed, let’s look at a little background of stem cells. We’ll stick to orthopedics for the sake of simplicity.
Orthopedic Stem Cell Therapy
Stem cells are naturally found in the human body and they are a fundamental part of the body’s normal healing process. Stem cells are known as ‘raw potential’ as they can be converted into any cell that the body needs. The body utilizes stem cells to substitute damaged and/or injured cells. This process allows natural healing and repair of the injured or damaged cells.
As the body gets older the amount of natural reserved stem cells starts to decline, which explains why the healing process is slower as the body gets older. Stem cell therapy resolves this shortage by injecting supplementary stem cells into the injured/damaged area of the body, which triggers the cell replacement, natural healing, and pain relief.
Stem cell therapy is a simple and quick procedure, taking about 15 minutes. Pain discomfort is often felt immediately, with the majority people reporting a significant improvement within one to two days.
With stem cell therapy the patient does not have to have any type of surgical procedure, local or general or downtime. Most of the patients experience a complete restoration of the damaged/ injured ligaments, tendons, and cartilage within about in 28 days. Stem cell therapy has been proven to be complexly safe, with no side effects reported in the US or in Europe.
The Difference Between Stem Cell Therapy and Platelet-Rich Plasma (PRP) Therapy
Often times, stem cell therapy and PRP can be confused because they have a lot in common during the healing process. The easiest way to tell the difference between the two, is PRP is removed from the patient’s own body, it goes through a scientific process and is them injected into the area being treated.
The cells used for stem cell therapy can come from a few different places; from an unviable embryo, and unviable fetal stem cells these stem cells are the most often used because the cells are unspecialized and can be made into specialized cells. As it sounds, preparing stem cells for therapy is a complex process. Stem cells are produced in a sophisticated labs by cell biologists and are typically grown over several weeks before it’s ready.
Plus, adult stem cells may be used, although it is not nearly as common yet because scientists are still working on ways to identify stem cells within the tissue of an adult human body.
Stem Cell Vs Platelet-Rich Plasma
So what’s the dark side of Stem Cell Therapy?
The obvious concern is that treatments with stem cells could be dangerous if not carefully controlled. I know we are all doing things for saving lives and helping people live longer, more happily, but the risks must also be considered.
Below are the 5 risks that stem cells carry. (which Platelet-Rich Plasma doesn’t.)
Risk of viruses: Since the stem cells are foreign bodies, if they happen to carry harmful microscopic agents, it’ll bring unnecessary complications. Especially those patients whose immune systems are weak, could be highly vulnerable diseases.
Uncontrolled growth: As I said before, stem cells are produced in a lab and grown over a period of several weeks. However, there is very tiny possibility the growth will continue uncontrolled after installing it into the patient. We pray it doesn’t happen.
Multi-tasking of cells: Stem cells are cultivated and grown into specialized cells that are designed to be doing just one thing and one thing only. But what if, in the long run, they also do other things that wasn’t in the original scope of things? Something to ponder.
That said, I still believe stem cells hold great promise. Now, I want to take this rest of the article to highlight a few of the common conditions that are found to be best for stem cell treatments.
Stem Cell Vs Platelet-Rich Plasma
Rheumatoid Arthritis
Rheumatoid Arthritis is caused by inflammation of the joints as a result of an autoimmune progression. The body’s immune system attacks the joints. Patients with Rheumatoid Arthritis suffer from mild to severe pain, constant fatigue, warm, and swollen joints. This type of chronic inflammation has the potential to easily damage the joints. Therefore, treatment is concentrated on decreasing the inflammation and slowing down the progress of the condition. Stem cell therapy provides a treatment alternative that takes advantage of the healing and anti-inflammatory effects.
Osteoarthritis
Osteoarthritis is joint inflammation caused by the deterioration of the cartilage that cause the bones to rub up against one another. Patients who suffer from osteoarthritis have pain, stiffness, and a decrease in their range of motion in their joints. Although, there is no cure for osteoarthritis, stem cell treatment focuses on reducing the pain reduction through medication, physical therapy, or occupational therapy. Stem cell therapy provides a treatment alternative that takes advantage of the healing and anti-inflammatory effects. While medication helps with the pain.
Shoulder Repair
Shoulder injuries such as rotator cuff tears and arthritis of the shoulder joint, as well as other types shoulder pain may be responsive to stem cell therapy. Stem cells goal is to renew damaged joints.
Stem Cell Treatment for Joint Repair
Hand and elbow problems caused by arthritis of the joints is a type of deteriorating joint disease that has disabled millions of people. Definite types of wrist and elbow joint issues including certain ligamentous injuries and tendon problems may not benefit from cell therapy. It is very important that the doctor evaluate each patient to see if stem cell therapy is a viable treatment for their patients.
Stem Cell Treatment for Knee
Knee arthritis is a type of deteriorating joint disease, which affects millions of people. Most people believe there only option for pain relief and better mobility is steroid injections or surgery, including total knee replacement surgery. However, that is not the case, many people benefit greatly from stem cell therapy. Specific types of knee issues such as, ligamentous injuries and substantial meniscal injuries may not be responsive to regenerative therapy (stem cell therapy). Each case must be carefully evaluated and the orthopedist will decide what options are best for the patient, in some cases, stem cell therapy is tried even if the patient is not exactly an ideal candidate, but trying is better than just scheduling surgery.
Stem Cell Treatment for Hip
Hip arthritis is similar to knee arthritis; millions of people suffer from hip problems. Patients usually try to delay the hip replacement surgery as long as they can and try other methods such as steroid injections, which for some people do help for a short period of time. However, long tern injects can damage the tissue near the hip. While fractured hips and certain kinds of hip injuries cannot be treated with stem cell therapy, surgery is the only available option left.
Stem Cell Treatment for Joint Repair
Problems with the hands and elbow joints usually respond well to stem cell therapy. If there are problems with the ligaments and tendons, then surgery may be necessary.
Degenerative joint diseases disable millions of people. While certain types of injuries are not a good match for stem cell therapy, there are several that are a good match. Before you prescribe surgery to repair damaged or injured joints consider about stem cell therapy, and if possible give it a try first.

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