Stem Cell Therapy Multiple Sclerosis

Transcription

1 Stem Cell Therapy Multiple Sclerosis What is multiple sclerosis? Multiple Sclerosis Multiple Sclerosis (MS) is caused by an immune mediated attack targeting components of the myelin sheath. The myelin sheath is known to act as an insulator for neurons so that they can communicate properly with each other. Can stem cells help treat multiple sclerosis? At present there are no treatments that specifically target the abnormal immune responses in MS. Current approaches, such as interferon, copaxone, or immune suppressants all act in a non specific manner blocking immune responses against the myelin sheath. While these approaches are useful for reducing the severity of disease, they do not repair the damage to nervous system tissue that has already occurred and therefore they cannot cure multiple sclerosis. Mesenchymal stem cells (MSCs), have immune regulatory properties which may stop the immune system from attacking the myelin sheath. Mesenchymal stem cells may also potentially help remyelination (re-generation of the myelin sheath) of the affected neurons. Currently, the University of Cambridge is conducting formal clinical studies using mesenchymal stem cells for treatment of MS. VIDEO Professor Arnold Caplan The father of mesenchymal stem cells from Case Western Reserve University discusses stem cell therapy for MS.

2 Which types of stem cells are used to treat MS and how are they obtained? The adult stem cells used to treat MS at the Stem Cell Institute are called allogeneic mesenchymal stem cells. They are harvested from human umbilical cords donated after normal, healthy births. Each mother is tested for infectious diseases and has her medical history screened. Proper consent is received from each family prior to donation. Before they are approved for use in treatment all umbilical cord-derived stem cells are screened for infectious diseases to International Blood Bank Standards. Only a small percentage of donated umbilical cords pass our rigorous screening process. Our stem cells and the US FDA Human umbilical cord tissue-derived mesenchymal stem cells (MSCs) that were isolated and grown in our laboratory in Panama to create master cell banks are currently being used in the United States. These cells serve as the starting material for cellular products used in MSC clinical trials for two Duchenne s muscular dystrophy patients under US FDA s designation of Investigational New Drug (IND) for single patient compassionate use. (IND DMD Single Patient) Dr. Riordan on the Umbilical Cord Selection Process at Stem Cell Institute Through retrospective analysis of our cases, we ve identified proteins and genes that allow us to screen several hundred umbilical cord donations to find the ones that we know are most effective. We only use these cells and we call them golden cells. We go through a very high throughput screening process to find cells that we know have the best anti-inflammatory activity, the best immune modulating capacity, and the best ability to stimulate regeneration. What are the advantages of treating with allogeneic human umbilical cord tissue (HUCT)-derived mesenchymal stem cells? Since HUCT mesenchymal stem cells are immune system privileged, cell rejection is not an issue and Human Leukocyte Antigen (HLA) matching is not necessary. The stem cells with the best anti-inflammatory activity, immune modulating capacity, and ability to stimulate regeneration can be screened and selected. Allogeneic stem cells can be administered multiple times over the course of days in uniform dosages that contain high cell counts. Umbilical cord tissue provides an abundant supply of mesenchymal stem cells. No need to collect stem cells through invasive procedures such as liposuction or bone marrow collection

3 There is a growing body of evidence showing that HUCT mesenchymal stem cells are more robust than mesenchymal stem cells from other sources such as fat. The body s immune system is unable to recognize umbilical cord-derived mesenchmyal stem cells as foreign and therefore they are not rejected. HUCT stem cells have been administered thousands of times at the Stem Cell Institute and there has never been a single instance rejection (graft vs. host disease). Umbilical cord-derived mesenchymal stem cells also proliferate/differentiate more efficiently than older cells, such as those found in the fat and therefore, they are considered to be more potent. In this next video (just past the 1 minute mark), Arnold Caplan, PhD explains the mechanism by which donor mesenchymal stem cells shield themselves from the recipient s immune system. Dr. Caplan is the scientist who discovered the mesenchymal stem cell. He is commonly referred to as the father of the mesenchymal stem cell. How are the stem cells administered for MS treatment? The HUCT stem cells are administered intravenously by a licensed physician. Additional methods may be recommended. Stem Cell Therapy for Multiple Sclerosis: *Treatment Protocols Below is an example of a typical 4-day multiple sclerosis treatment *protocol: Medical evaluation, blood testing 6 intravenous injections of human umbilical cord tissue-derived mesenchymal stem cells 4 perilymphatic injections of HUCT mesenchymal stem cells 2 physical therapy sessions

4 Stem Cell Therapy Spinal Cord Injury About spinal cord injury Spinal Cord Injury Spinal cord injury (SCI) occurs when the spinal cord becomes damaged, most commonly, when motor vehicle accidents, falls, acts of violence, or sporting accidents fracture vertebrae and crush or transect the spinal cord. Damage to the spinal cord usually results in impairments or loss of muscle movement, muscle control, sensation and body system control. Can stem cells help treat spinal cord injury? Presently, post-accident care for spinal cord injury patients focuses on extensive physical therapy, occupational therapy, and other rehabilitation therapies; teaching the injured person how to cope with their disability. A number of published papers and case studies support the feasibility of treating spinal cord injury with allogeneic human umbilical cord tissue-derived stem cells and autologous bone marrow-derived stem cells. Feasibility of combination allogeneic stem cell therapy for spinal cord injury: a case report co-authored by Stem Cell Institute Founder Dr. Neil Riordan references many of them. Published improvements include improved ASIA scores, improved bladder and/or bowel function, recovered sexual function, and increased muscle control.

5 Which types of stem cells does the Stem Cell Institute use to treat spinal cord injury and how are they collected? The adult stem cells used to treat spinal cord injuries at the Stem Cell Institute come from two sources: the patient s own bone marrow (autologous mesenchymal and CD34+) and human umbilical cord tissue(allogeneic mesenchymal). Umbilical cords are donated by mothers after normal, healthy births. A licensed anesthesiologist harvests bone marrow from both hips under light general anesthesia in a hospital operating room. This procedure takes about 1 1/2 2 hours. Before they are administered to the patient, these bone marrow-derived stem cells must pass testing for quality, bacterial contamination (aerobic and anaerobic) and endotoxin. All donated umbilical cords are screened for viruses and bacteria to International Blood Bank Standards. Only a small percentage of donated umbilical cords pass our rigorous screening process. Dr. Riordan on the Umbilical Cord Selection Process at Stem Cell Institute Through retrospective analysis of our cases, we ve identified proteins and genes that allow us to screen several hundred umbilical cord donations to find the ones that we know are most effective. We only use these cells and we call them golden cells. We go through a very high throughput screening process to find cells that we know have the best anti-inflammatory activity, the best immune modulating capacity, and the best ability to stimulate regeneration. Our stem cells and the US FDA Human umbilical cord tissue-derived mesenchymal stem cells (MSCs) that were isolated and grown in our laboratory in Panama to create master cell banks are currently being used in the United States. These cells serve as the starting material for cellular products used in MSC clinical trials for two Duchenne s muscular dystrophy patients under US FDA s designation of Investigational New Drug (IND) for single patient compassionate use. (IND DMD Single Patient) What are the advantages of treating spinal cord injury with allogeneic human umbilical cord tissue (HUCT)- derived mesenchymal stem cells? Since HUCT mesenchymal stem cells are immune system privileged, cell rejection is not an issue and Human Leukocyte Antigen (HLA) matching is not necessary.

6 The stem cells with the best anti-inflammatory activity, immune modulating capacity, and ability to stimulate regeneration can be screened and selected. Allogeneic stem cells can be administered multiple times over the course of days in uniform dosages that contain high cell counts. Umbilical cord tissue provides an abundant supply of mesenchymal stem cells. There is a growing body of evidence showing that HUCT mesenchymal stem cells are more robust than mesenchymal stem cells from other sources such as fat. The body s immune system is unable to recognize umbilical cord-derived mesenchmyal stem cells as foreign and therefore they are not rejected. HUCT stem cells have been administered thousands of times at the Stem Cell Institute and there has never been a single instance rejection (graft vs. host disease). Umbilical cord-derived mesenchymal stem cells also proliferate/differentiate more efficiently than older cells, such as those found in the fat and therefore, they are considered to be more potent. In this next video (just past the 1 minute mark), Arnold Caplan, PhD explains the mechanism by which donor mesenchymal stem cells shield themselves from the recipient s immune system. Dr. Caplan is the scientist who discovered the mesenchymal stem cell. He is commonly referred to as the father of the mesenchymal stem cell. How do the physicians administer these stem cells? Our stem cell treatment protocol for spinal cord injury calls for a total of 16 injections over the course of 4 weeks. The bone marrow-derived and umbilical cord tissue-derived stem cells are both administered intravenously by a licensed physician. They are also injected intrathecally (into the spinal fluid) by an experienced anesthesiologist. Intrathecal injection enables the stem cells to bypass the blood-brain barrier and migrate to the injury site within the spinal canal. Spinal cord injury stem cell treatment protocol The standard protocol takes 4 weeks Medical evaluation, blood testing, and bone marrow collection 8 intrathecal (spinal canal) injections of expanded umbilical cord tissue-derived stem cells 4 intravenous injections (IV) expanded umbilical cord tissue-derived stem cells 2 intrathecal (lumbar puncture) injections of bone marrow-derived stem cells 2 intravenous injections (IV) bone marrow-derived stem cells (upon availability after IT injections) 12 physical therapy sessions

7 Stem Cell Therapy Autism What is autism? Autism Treatment Autism is a spectrum of disorders characterized by marked abnormalities in communication and social interactions. Two common consistent findings are associated in children with this disorder are diminished oxygenation in specific areas of the brain and a chronic immunologically mediated inflammatory condition in the gut. What is the rationale behind using stem cells to treat autism? Current investigative therapies for autism attempt to reverse these abnormalities through administration of antibiotics, anti inflammatory agents, and hyperbaric oxygen. Unfortunately, none of these approaches address the root causes of oxygen deprivation and intestinal inflammation. The rationale behind treating autism with umbilical cord tissue-derived mesenchymal stem cells is that autism, and its degree of severity, has been significantly correlated inflammatory and neuro-inflammatory cytokines including macrophage-derived chemokine (MDC) and thymus and activation-regulated chemokine (TARC). Intravenous administration of umbilical cord MSCs has been shown in multiple clinical trials to decrease inflammation. Decreasing inflammation in the autistic patient may alleviate symptoms of autism. Through administration of mesenchymal stem cells, we have observed improvement in patients treated at our facilities. Related Scientific Publications:

8 Elevated serum levels of macrophage-derived chemokine and thymus and activationregulated chemokine in autistic children Journal of Neuroinflammation Stem Cell Therapy for Autism Journal of Translational Medicine Which types of stem cells are used to treat autism and how are they obtained? The adult stem cells used to treat autism at the Stem Cell Institute come from human umbilical cord tissue (allogeneic mesenchymal). Umbilical cords are donated by mothers after normal, healthy births. Before they are approved for treatment all umbilical cordderived stem cells are screened for viruses and bacteria to International Blood Bank Standards. In some cases, we also utilize stem cells harvested from the patient s own bone marrow. Umbilical cord-derived stem cells are ideal for the treatment of autism because they allow our physicians to administer uniform doses and they do not require any stem cell collection from the patient, which for autistic children and their parents, can be an arduous process. Because they are collected right after (normal) birth, umbilical cord-derived cells are much more potent than their older counterparts like bone marrow-derived cells for instance. Cord tissue-derived mesenchymal stem cells pose no rejection risk because the body does not recognize them as foreign. Dr. Riordan on the Umbilical Cord Selection Process at Stem Cell Institute Through retrospective analysis of our cases, we ve identified proteins and genes that allow us to screen several hundred umbilical cord donations to find the ones that we know are most effective. We only use these cells and we call them golden cells. We go through a very high throughput screening process to find cells that we know have the best anti-inflammatory activity, the best immune modulating capacity, and the best ability to stimulate regeneration. Our stem cells and the US FDA Human umbilical cord tissue-derived mesenchymal stem cells (MSCs) that were isolated and grown in our laboratory in Panama to create master cell banks are currently being used in the United States. These cells serve as the starting material for cellular products used in MSC clinical trials for two Duchenne s muscular dystrophy patients under US FDA s designation of Investigational New Drug (IND) for single patient compassionate use. (IND DMD Single Patient) What are the advantages of treating with allogeneic umbilical cord tissue-derived stem cells?

9 Since HUCT mesenchymal stem cells are immune system privileged, cell rejection is not an issue and Human Leukocyte Antigen (HLA) matching is not necessary. The stem cells with the best anti-inflammatory activity, immune modulating capacity, and ability to stimulate regeneration can be screened and selected. Allogeneic stem cells can be administered multiple times over the course of days in uniform dosages that contain high cell counts. Umbilical cord tissue provides an abundant supply of mesenchymal stem cells. No need to collect stem cells from the patient s hip bone or fat under anesthesia, which especially for small children and their parents, can be an unpleasant ordeal. There is a growing body of evidence showing that umbilical cord-derived mesenchymal stem cells are more robust than mesenchymal stem cells from other sources. The body s immune system is unable to recognize umbilical cord-derived mesenchymal stem cells as foreign and therefore they are not rejected. HUCT stem cells have been administered thousands of times at the Stem Cell Institute and there has never been a single instance rejection (graft vs. host disease). Umbilical cord-derived mesenchymal stem cells also proliferate/differentiate more efficiently than older cells, such as those found in the fat and therefore, they are considered to be more potent. In this next video (just past the 1 minute mark), Arnold Caplan, PhD explains the mechanism by which donor mesenchymal stem cells shield themselves from the recipient s immune system. Dr. Caplan is the scientist who discovered the mesenchymal stem cell. He is commonly referred to as the father of the mesenchymal stem cell. How are the stem cells administered for autism treatment? The umbilical cord-derived stem cells are administered intravenously by a licensed physician. Stem Cell Treatment: Autism *Protocols *NOTE Treatment protocol will be assigned by staff physicians after the patient has submitted all requested medical information and received approval. A patient s recommended protocol may differ from the example given below. Below is an example of a typical autism *protocol: Treatment length Physical examination and blood testing: Monday 4 intravenous infusions of human umbilical cord tissue-derived allogeneic mesenchymal stem cells: Tuesday Friday Scientific Articles Stem Cell Therapy for Autism Ichim T, Solano F, Glenn E, Morales F, Smith L, Zabrecky G, Riordan Neil. Journal of Translational Medicine 2007, 5:30

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11 Stem Cell Therapy Cerebral Palsy What is cerebral palsy? Cerebral Palsy Cerebral palsy is a condition that results from injuries or abnormalities of the brain, usually in the womb but occurring any time during 2 years after birth. It affects brain and nervous system functions such as thinking, seeing, hearing, learning and movement. Common causes are hypoxia (low oxygen levels), head injury, maternal infections such as rubella, brain bleeding, brain infection, and severe jaundice. Types of CP include: ataxic, hypotonic, spastic, dyskinetic, and mixed. Can cerebral palsy be treated with stem cells? Mesenchymal stem cells from umbilical cord are considered to be universal donor cells because they are not immediately recognized as foreign. The cells home to damaged tissue and are known to secrete molecules called trophic factors. Trophic factors from mesenchymal stem cells are known to stimulate repair of damaged nervous tissue in both the brain and the spinal cord. Some of these are neurotrophic factors that promote neuronal growth, induce new blood vessel growth, neurogenesis and astroglial activation, encourage synaptic connection and axonal remyelination, decrease programed cell death, and regulate microglial activation. 1 Mesenchymal stem cells stimulate brain repair after stroke1 and traumatic brain injury. 2,3,4 Animal studies show that mesenchymal stem cell can migrate into the brain and survive. 5,6,7 Because we utilize allogeneic cord tissue-derived mesenchymal stem cells, we are able to offer treatment to any qualified patient, not just those who saved their own cord blood at

12 birth. We will discuss several additional advantages of allogeneic cord-derived stem cells below. There is evidence to support that bone marrow-derived mononuclear cells are safe and improve the quality of life in children with neurological disorders including cerebral palsy. 8 Which kinds of stem cells are utilized for CP treatment and how are they collected? The Stem Cell Institute leverages adult stem cells from human umbilical cord tissue to treat cerebral palsy. Umbilical cords are donated by mothers after normal, healthy births. In accordance with International Blood Bank standards, all umbilical cord-derived stem cells are rigorously screened for viruses and bacteria at Medistem Labs before they are approved for use in patients. In some cases, stem cells harvested from the patient s own bone marrow are used in addition to umbilical cord tissue-derived cells. The body s immune system is unable to recognize umbilical cord-derived mesenchymal stem cells as foreign and therefore they are not rejected. We ve treated hundreds of patients with umbilical cord stem cells and there has never been a single instance rejection (graft vs. host disease). HUCT stem cells also proliferate/differentiate more efficiently than older cells, such as those found in the bone marrow and therefore, they are considered to be more potent. Our stem cells and the US FDA Human umbilical cord tissue-derived mesenchymal stem cells (MSCs) that were isolated and grown in our laboratory in Panama to create master cell banks are currently being used in the United States. These cells serve as the starting material for cellular products used in MSC clinical trials for two Duchenne s muscular dystrophy patients under US FDA s designation of Investigational New Drug (IND) for single patient compassionate use. (IND DMD Single Patient) What are the advantages of treating with allogeneic umbilical cord tissue-derived stem cells? Since HUCT mesenchymal stem cells are immune system privileged, cell rejection is not an issue and Human Leukocyte Antigen (HLA) matching is not necessary. The stem cells with the best anti-inflammatory activity, immune modulating capacity, and ability to stimulate regeneration can be screened and selected. Allogeneic stem cells can be administered multiple times over the course of days in uniform dosages that contain high cell counts. Umbilical cord tissue provides an abundant supply of mesenchymal stem cells. No need to collect stem cells from the patient s hip bone or fat under anesthesia, which especially for small children and their parents, can be an unpleasant ordeal.

13 There is a growing body of evidence showing that umbilical cord-derived mesenchymal stem cells are more robust than mesenchymal stem cells from other sources. In this next video (just past the 1 minute mark), Arnold Caplan, PhD explains the mechanism by which donor mesenchymal stem cells shield themselves from the recipient s immune system. Dr. Caplan is the scientist who discovered the mesenchymal stem cell. He is commonly referred to as the father of the mesenchymal stem cell. Dr. Riordan on the Umbilical Cord Selection Process at Stem Cell Institute Through retrospective analysis of our cases, we ve identified proteins and genes that allow us to screen several hundred umbilical cord donations to find the ones that we know are most effective. We only use these cells and we call them golden cells. We go through a very high throughput screening process to find cells that we know have the best anti-inflammatory activity, the best immune modulating capacity, and the best ability to stimulate regeneration. How are the stem cells administered during CP treatment? A licensed physician administers the stem cells intravenously (IV). Stem Cell Treatment Protocol for Cerebral Palsy *NOTE Treatment protocol will be assigned by staff physicians after the patient has submitted all requested medical information and received approval. A patient s recommended protocol may differ from the example given below. Below is an example of a typical cerebral palsy *protocol: 4 intravenous infusions of human umbilical cord tissue-derived allogeneic mesenchymal stem cells Scientific Articles Cord Blood in Regenerative Medicine: Do We Need Immune Suppression? Riordan Neil, Chan K, Marleau A, Ichim T. Journal of Translational Medicine 2007, 5:8 1. Jung Hwa Seo, Sung-Rae Cho. Neurorestoration Induced by Mesenchymal Stem Cells: Potential Therapeutic Mechanisms for Clinical Trials Yonsei Med J November 1; 53(6): Li Y, Chopp M. Marrow stromal cell transplantation in stroke and traumatic brain injury.neurosci Lett. 2009;456(3):

14 3. Kassem M, Abdallah BM. Human bone-marrow-derived mesenchymal stem cells: biological characteristics and potential role in therapy of degenerative diseases. Cell Tissue Res.2008;331(1): Greco SJ, Rameshwar P. Enhancing effect of IL-1alpha on neurogenesis from adult human mesenchymal stem cells: implication for inflammatory mediators in regenerative medicine. J Immunol. 2007;179(5): Lu D, Li Y, Wang L, Chen J, Mahmood A, Chopp M. Intraarterial administration of marrow stromal cells in a rat model of traumatic brain injury. J Neurotrauma. 2001;18(8): Lu D, Mahmood A, Wang L, Li Y, Lu M, Chopp M. Adult bone marrow stromal cells administered intravenously to rats after traumatic brain injury migrate into brain and improve neurological outcome. Neuroreport. 2001;12(3): Chen J, Li Y, Wang L, Lu M, Zhang X, Chopp M. Therapeutic benefit of intracerebral transplantation of bone marrow stromal cells after cerebral ischemia in rats. J Neurol Sci.2001;189(1 2): Sharma A, Gokulchandran N, Chopra G, Kulkarni P, Lohia M, Badhe P, Jacob VC. Administration of autologous bone marrow-derived mononuclear cells in children with incurable neurological disorders and injury is safe and improves their quality of life. Cell Transplant. 2012;21 Suppl 1:S doi: / X

15 Stem Cell Therapy Heart Failure What is heart failure? Heart Disease Heart failure is a condition in which the heart is not able to pump enough blood throughout the body for its normal function. The cause of this can be either functional or structural disorder of the heart. Common causes of heart failure include cardiomyopathy, hypertension, heart valve problems and coronary artery disease. There is no heart failure cure. Can stem cells help treat heart failure? With respect to the heart, stem cells have the ability to not only home into the damaged areas but also to initiate a cascade of biological events which both culminate in healing of the heart muscle. For example, animal studies have demonstrated that stem cell therapy will cause new muscle cells to be formed through stimulation of dormant stem cells that are already inside the heart muscle. In these studies, the administered stem cell also transformed into new heart muscle cells. At Stem Cell Institute, our stem cell treatment protocol for heart failure involves administration of mesenchymal stem cells harvested from human umbilical cord tissue. Which kinds of stem cells are used to treat heart failure and where do they come from?

16 The adult stem cells used to treat heart failure at the Stem Cell Institute come from human umbilical cord tissue (allogeneic mesenchymal). These stem cells are expanded at Medistem Panama s state-of-the-art laboratory. The mesenchymal stem cells we use are recovered from donated umbilical cords following normal, healthy births. Each mother has her medical history screened and is tested for infectious diseases. Proper consent is received from each family prior to donation. All umbilical cord-derived stem cells are screened for infectious diseases to International Blood Bank Standards before they are cleared for use in patients. Only a small percentage of donated umbilical cords pass our rigorous screening process. Our stem cells and the US FDA Human umbilical cord tissue-derived mesenchymal stem cells (MSCs) that were isolated and grown in our laboratory in Panama to create master cell banks are currently being used in the United States. These cells serve as the starting material for cellular products used in MSC clinical trials for two Duchenne s muscular dystrophy patients under US FDA s designation of Investigational New Drug (IND) for single patient compassionate use. (IND DMD Single Patient) Dr. Riordan on the Umbilical Cord Selection Process at Stem Cell Institute Through retrospective analysis of our cases, we ve identified proteins and genes that allow us to screen several hundred umbilical cord donations to find the ones that we know are most effective. We only use these cells and we call them golden cells. We go through a very high throughput screening process to find cells that we know have the best anti-inflammatory activity, the best immune modulating capacity, and the best ability to stimulate regeneration. What are the advantages of treating with allogeneic human umbilical cord tissue (HUCT)-derived mesenchymal stem cells? Since HUCT mesenchymal stem cells are immune system privileged, cell rejection is not an issue and Human Leukocyte Antigen (HLA) matching is not necessary. The stem cells with the best anti-inflammatory activity, immune modulating capacity, and ability to stimulate regeneration can be screened and selected. Allogeneic stem cells can be administered multiple times over the course of days in uniform dosages that contain high cell counts. Umbilical cord tissue provides an abundant supply of mesenchymal stem cells. No need to collect stem cells through invasive procedures such as liposuction or bone marrow collection There is a growing body of evidence showing that HUCT mesenchymal stem cells are more robust than mesenchymal stem cells from other sources such as fat.

17 The body s immune system is unable to recognize umbilical cord-derived mesenchmyal stem cells as foreign and therefore they are not rejected. HUCT stem cells have been administered thousands of times at the Stem Cell Institute and there has never been a single instance rejection (graft vs. host disease). Umbilical cord-derived mesenchymal stem cells also proliferate/differentiate more efficiently than older cells, such as those found in the fat and therefore, they are considered to be more potent. Watch Professor Arnold Caplan from Case Western Reserve University explain how this works. How are the stem cells administered for heart failure treatment? A licensed physician administers the stem cells via intravenous and intramuscular injections over the course of a few days. Heart Failure Stem Cell Treatment Protocol Here is an example of a typical protocol for *heart failure. Medical evaluation and blood testing 5 IV injections of expanded allogeneic (low-passage) mesenchymal stem cells 8 intramuscular injections of expanded allogeneic mesenchymal stem cells 2 IV Vitamin C infusion (depending on the patients renal function)

18 Stem Cell Therapy Osteoarthritis What is osteoarthritis? Osteoarthritis Treatment Osteoarthritis, also known as degenerative arthritis or degenerative joint disease, is a group of mechanical abnormalities involving degradation of joints, including articular cartilage and subchondral bone. Symptoms may include joint pain, tenderness, stiffness, locking, and sometimes an effusion. When bone surfaces become less well protected by cartilage, bone may be exposed and damaged. As a result of decreased movement secondary to pain, regional muscles may atrophy, and ligaments may become more lax. How can stem cells help fight arthritis? Stem cell therapy has been demonstrated to induce profound healing activity in animals with various forms of arthritis. For example, the company Vet-Stem routinely utilizes stem cells in horses with various joint deformities to accelerate healing. Besides healing of damaged tissues, stem cells have the unique ability to modulate the immune system so as to shut off pathological responses while preserving ability to fight off disease. Which kinds of stem cells are used and how are they obtained? The stem cells we use are called allogeneic mesenchymal stem cells and they are considered to be adult stem cells, not fetal or embryonic. These cells are harvested from donated human umbilical cords after normal, healthy births. Each mother is tested for infectious diseases and has her medical history screened. Proper written consent is obtained from each family prior to donation.

19 Before they are cleared by the lab for treatments, all of the mesenchymal stem cells are screened for infectious diseases to International Blood Bank Standards. Only a small percentage of umbilical cords make it past our rigorous screening process. Dr. Riordan on the Umbilical Cord Selection Process at Stem Cell Institute Through retrospective analysis of our cases, we ve identified proteins and genes that allow us to screen several hundred umbilical cord donations to find the ones that we know are most effective. We only use these cells and we call them golden cells. We go through a very high throughput screening process to find cells that we know have the best anti-inflammatory activity, the best immune modulating capacity, and the best ability to stimulate regeneration. What are the advantages of treating with allogeneic human umbilical cord tissue (HUCT)-derived mesenchymal stem cells? Since HUCT mesenchymal stem cells are immune system privileged, cell rejection is not an issue and Human Leukocyte Antigen (HLA) matching is not necessary. The stem cells with the best anti-inflammatory activity, immune modulating capacity, and ability to stimulate regeneration can be screened and selected. Allogeneic stem cells can be administered multiple times over the course of days in uniform dosages that contain high cell counts. Umbilical cord tissue provides an abundant supply of mesenchymal stem cells. No need to collect stem cells through invasive procedures such as liposuction or bone marrow collection There is a growing body of evidence showing that mesenchymal stem cells from umbilical cords are more robust than mesenchymal stem cells from other sources such as fat. The body s immune system is unable to recognize human umbilical cord tissue (HUCT)- derived mesenchmyal stem cells as foreign and therefore they are not rejected. HUCT stem cells have been administered thousands of times at the Stem Cell Institute and there has never been a single instance rejection (graft vs. host disease). Umbilical cord-derived mesenchymal stem cells also proliferate/differentiate more efficiently than older cells, such as those found in the fat and therefore, they are considered to be more potent. In this next video (just past the 1 minute mark), Arnold Caplan, PhD explains the mechanism by which donor mesenchymal stem cells shield themselves from the recipient s immune system. Dr. Caplan is the scientist who discovered the mesenchymal stem cell. He is commonly referred to as the father of the mesenchymal stem cell. Our stem cells and the US FDA

20 Human umbilical cord tissue-derived mesenchymal stem cells (MSCs) that were isolated and grown in our laboratory in Panama to create master cell banks are currently being used in the United States. These cells serve as the starting material for cellular products used in MSC clinical trials for two Duchenne s muscular dystrophy patients under US FDA s designation of Investigational New Drug (IND) for single patient compassionate use. (IND DMD Single Patient) How are the stem cells administered? The stem cells are administered by a licensed physician into the affected joint(s) (intraarticular injection) and intravenously (IV). In certain circumstances, stem cells may also be administered intrathecally and/or intramuscularly. Extra intra-articular injections for multiple joints can be arranged as medical requirements dictate. Osteoarthritis Stem Cell Treatment *Protocol A typical treatment protocol takes about 4 days. Below is an example. Medical evaluation and blood testing 1 2 Intra-articular (into the joint) injections of HUCT mesenchymal stem cells as needed 5 Intravenous injections (IV) of HUCT mesenchymal stem cells

21 Stem Cell Therapy Rheumatoid Arthritis What is Rheumatoid Arthritis? Rheumatoid Arthritis Rheumatoid Arthritis (RA) is an autoimmune disease in which the patient s immune system generates cellular and antibody responses to various components of the joint such as type I collagen. As a result of this immune response, not only does joint destruction occur, but also other secondary complications such as pulmonary fibrosis, renal damage, and even heart damage. Can stem cells help treat rheumatoid arthritis? Newly diagnosed rheumatoid arthritis is currently treated with immune suppressive agents such as steroids, methothrexate, cyclosporine, gold, and more recently infliximab (Remicade). Despite inducing temporary improvement, these approaches possess longterm adverse effects due to non-specific inhibition of immune responses. When diseasemodifying anti-rheumatic drugs (DMARDs) like methotrexate are not effective, biologics like abatacept (Orencia), adalimumab (Humira) or etanercept (Enbrel) may be recommended. None of these treatments address the issue of damage that has already occurred to the joints or extra-articular tissues. Even though advancements in rheumatoid arthritis (RA) treatment protocols and introduction of targeted biological therapies have markedly improved patient outcomes, up to 50% of patients still fail to achieve a significant clinical response.

22 Stem cell therapy has been demonstrated to induce profound healing activity in animals with various forms of arthritis. For example, the company Vet-Stem routinely utilizes stem cells in horses with various joint deformities to accelerate healing. Besides healing of damaged tissues, stem cells have the unique ability to modulate the immune system so as to shut off pathological responses while preserving ability to fight off disease. Stem cells and specifically, mesenchymal stem cells (MSCs) home to inflamed tissue and start producing anti-inflammatory agents. These mediators act locally and do not suppress the immune response of the patient s whole body. Additionally, MSCs induce the production of T regulatory cells, a type of immune cell whose function is to protect the body against immunological self-attack. A recent study on MSCs for rheumatoid arthritis (Human Umbilical Cord Mesenchymal Stem Cell Therapy for Patients with Active Rheumatoid Arthritis: Safety and Efficacy) showed that MSCs produced a significant decrease in pro-inflammatory cytokines IL-6 and TNF-α, both of which are temporarily targeted by many current RA treatments. without the long-term side effects. These decreases are shown in Figure 5 from the original publication. Which kinds of stem cells are used to treat rheumatoid arthritis and how are they obtained? The Stem Cell Institute uses adult stem cells called allogeneic mesenchymal stem cells to treat rheumatoid arthritis. These cells are harvested from human umbilical cords donated after normal, healthy births. All mothers who donate umbilical cords undergo infectious disease testing and medical history screening. Proper written consent is obtained from each family prior to umbilical cord donation.

23 All mesenchymal stem cells harvested from umbilical cords are screened for infectious diseases to International Blood Bank Standards before they are cleared for use in treatments. Only a small percentage of umbilical cords pass our rigorous screening process. Dr. Riordan on the Umbilical Cord Selection Process at Stem Cell Institute Through retrospective analysis of our cases, we ve identified proteins and genes that allow us to screen several hundred umbilical cord donations to find the ones that we know are most effective. We only use these cells and we call them golden cells. We go through a very high throughput screening process to find cells that we know have the best anti-inflammatory activity, the best immune modulating capacity, and the best ability to stimulate regeneration. Our stem cells and the US FDA Human umbilical cord tissue-derived mesenchymal stem cells (MSCs) that were isolated and grown in our laboratory in Panama to create master cell banks are currently being used in the United States. These cells serve as the starting material for cellular products used in MSC clinical trials for two Duchenne s muscular dystrophy patients under US FDA s designation of Investigational New Drug (IND) for single patient compassionate use. (IND DMD Single Patient) What are the advantages of treating with allogeneic human umbilical cord tissue (HUCT)-derived mesenchymal stem cells? Allogeneic stem cells can be administered multiple times over the course of days in uniform dosages that contain high cell counts. The stem cells with the best anti-inflammatory activity, immune modulating capacity, and ability to stimulate regeneration can be screened and selected. Umbilical cord tissue provides an abundant supply of mesenchymal stem cells. No need to collect stem cells through invasive procedures such as liposuction or bone marrow collection Since HUCT mesenchymal stem cells are immune system privileged, cell rejection is not an issue and Human Leukocyte Antigen (HLA) matching is not necessary. There is a growing body of evidence showing that mesenchymal stem cells from umbilical cords are more robust than mesenchymal stem cells from other sources such as fat. The body s immune system is unable to recognize human umbilical cord tissue (HUCT)- derived mesenchmyal stem cells as foreign and therefore they are not rejected. HUCT stem cells have been administered thousands of times at the Stem Cell Institute and there has never been a single instance rejection (graft vs. host disease). Umbilical cord-derived

24 mesenchymal stem cells also proliferate/differentiate more efficiently than older cells, such as those found in the fat and therefore, they are considered to be more potent. In this next video (just past the 1 minute mark), Arnold Caplan, PhD explains the mechanism by which donor mesenchymal stem cells shield themselves from the recipient s immune system. Dr. Caplan is the scientist who discovered the mesenchymal stem cell. He is commonly referred to as the father of the mesenchymal stem cell. How are mesenchymal stem cells administered for rheumatoid arthritis treatment? They are typically given intravenously (IV) over the course of a few days. Rheumatoid Arthritis Stem Cell Treatment *Protocol Below is an example of a typical 4-day rheumatoid arthritis treatment protocol. Medical evaluation and blood testing 6 IV injections of allogeneic umbilical cord mesenchymal stem cells Scientific Articles Antigen Specific Therapy of Rheumatoid Arthritis Ichim T. Zheng X, Suzuki M, Kubo N, Zhang X, Min L, Beduhn M, Riordan N, Inman R, Min W. Expert opin. Biol. Ther. 2008; 8(2): Human Umbilical Cord Mesenchymal Stem Cell Therapy for Patients with Active Rheumatoid Arthritis: Safety and Efficacy Liming Wang, Lihua Wang, Xiuli Cong, Guangyang Liu, Jianjun Zhou, Bin Bai, Yang Li, Wen Bai, Ming Li, Haijie Ji, Delin Zhu, Mingyuan Wu and Yongjun Liu Stem Cells Dev Dec 15;22(24): doi: /scd Epub 2013 Oct 4.

25 Stem Cell Therapy Autoimmune Diseases What are autoimmune diseases? Autoimmune Diseases Treatment Autoimmune diseases are conditions in which the patient s immune system generates cellular and antibody responses to substances and tissues normally present in the body. This might be restricted to one organ or involve a particular tissue in different places. As a result of this immune response, damage to different organs occurs. Examples of autoimmune diseases that have responded to stem cell therapy either in animals or humans include rheumatoid arthritis, multiple sclerosis, and lupus. How can stem cells help treat autoimmune diseases? Currently, autoimmune conditions are treated with immune suppressive agents such as steroids, methothrexate, cyclosporine, gold, and more recently infliximab (Remicade). Despite inducing temporary improvement, these approaches possess the possibility of longterm adverse effects, as well as need for life-long treatment. Stem cell therapy has been demonstrated to induce profound healing activity in animals with various forms of autoimmune disorders. Besides healing damaged tissues, stem cells have the unique ability to modulate the immune system so as to shut off pathological responses while preserving its ability to fight off disease. Stem cells and specifically, mesenchymal stem cells home to inflamed tissue and start producing anti-inflammatory agents. These mediators act locally and do not suppress the immune response of the patient s whole body. Additionally, mesenchymal stem cells induce the production of T regulatory cells, a type of immune cell whose function is to protect the body against immunological self-attack.

26 Which kinds of stem cells are used and how are they obtained? We use adult stem cells called allogeneic mesenchymal stem cells. We harvest them from human umbilical cords donated after normal, healthy births. All donating mothers are tested for infectious diseases and have their medical histories screened. We obtain proper consent from each family prior to umbilical cord donation. All mesenchymal stem cells harvested from umbilical cords are screened for infectious diseases to International Blood Bank Standards before they are approved for use in treatments. Only a small percentage of donated umbilical cords pass our rigorous screening process. Dr. Riordan on the Umbilical Cord Selection Process at Stem Cell Institute Through retrospective analysis of our cases, we ve identified proteins and genes that allow us to screen several hundred umbilical cord donations to find the ones that we know are most effective. We only use these cells and we call them golden cells. We go through a very high throughput screening process to find cells that we know have the best anti-inflammatory activity, the best immune modulating capacity, and the best ability to stimulate regeneration. Our stem cells and the US FDA Human umbilical cord tissue-derived mesenchymal stem cells (MSCs) that were isolated and grown in our laboratory in Panama to create master cell banks are currently being used in the United States. These cells serve as the starting material for cellular products used in MSC clinical trials for two Duchenne s muscular dystrophy patients under US FDA s designation of Investigational New Drug (IND) for single patient compassionate use. (IND DMD Single Patient) What are the advantages of treating with allogeneic human umbilical cord tissue (HUCT)-derived mesenchymal stem cells? Anyone can be treated since HUCT mesenchymal stem cells are immune system privileged. Human Leukocyte Antigen (HLA) matching is not necessary. The stem cells with the best anti-inflammatory activity, immune modulating capacity, and ability to stimulate regeneration can be screened and selected. Allogeneic stem cells can be administered multiple times over the course of days in uniform dosages that contain high cell counts. Umbilical cord tissue provides an abundant supply of mesenchymal stem cells.

27 No need to collect stem cells through invasive procedures such as liposuction or bone marrow collection There is a growing body of evidence showing that mesenchymal stem cells from umbilical cords are more robust than mesenchymal stem cells from other sources such as fat. The body s immune system is unable to recognize human umbilical cord tissue (HUCT)- derived mesenchmyal stem cells as foreign and therefore they are not rejected. HUCT stem cells have been administered thousands of times at the Stem Cell Institute and there has never been a single instance rejection (graft vs. host disease). Umbilical cord-derived mesenchymal stem cells also proliferate/differentiate more efficiently than older cells, such as those found in the fat and therefore, they are considered to be more potent. In this next video (just past the 1 minute mark), Arnold Caplan, PhD explains the mechanism by which donor mesenchymal stem cells shield themselves from the recipient s immune system. Dr. Caplan is the scientist who discovered the mesenchymal stem cell. He is commonly referred to as the father of the mesenchymal stem cell. How are the stem cells administered? The HUCT-derived stem cells are typically administered intravenously by a licensed physician over the course of a few days. Stem Cell Therapy for Autoimmune Diseases Below is an example of a typical 4-day treatment *protocol: Medical evaluation and blood testing 6 intravenous (IV) injections of human umbilical cord tissue-derived mesenchymal stem cells