Exosomes as a. Novel Therapeutic Approach to Gastrointestinal Diseases Rebecca Murray APRN, FNP, CDE
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1 Exosomes as a Novel Therapeutic Approach to Gastrointestinal Diseases Rebecca Murray APRN, FNP, CDE Endocrine Nurse Practitioner Institute for Hormonal Balance Orlando, FL Medical Director Ward-Murray Healthcare & Consulting Orlando, FL Scientific Advisory Board Designs for Health
2 Disclosures Medical Consultant CrohnsColitisLifestyle.com On-line consultations for alternative healing strategies for GI diseases Board Member efundyourhealth.com Crowd-funding Platform for raising money to cover costs of alternative medicine treatment for Crohns/Colitis and other diseases Scientific Advisory Board Practitioner Development Consultant Designs for Health
3 Crohn s Ds: The Journey of a 2 month hospital stay Used with permission of patient
4 Review of the Literature Baghaei K, Tokhanbigli S, Asadzadeh H, Nmaki S, Zali MR, Hashemi SM. Exosomes as a novel cell-free therapeutic approach in gastrointestinal diseases. J Cell Physiol. 2018;
5 Exosomes in GI Diseases: Abstract Cell communication through extracellular vesicles (EVs) has been defined for many years and it is not limited only to neighboring cells, but also distant ones in organisms receive these signals. These vesicles are secreted from the variety of cells and are composed of a distinctive component such as proteins, lipids, and nucleic acids. EVs have different classified subgroups regarding their cell origin, in this context, exosomes are the most appealing particles in cell biology, especially clinical in recent years and are represented as novel therapeutic agents with numerous advantage alongside and/or over cell therapy.
6 Exosomes in GI Diseases: Abstract (con t) However, cell therapy had a hopeful outcome in gastrointestinal diseases which have minimal alternatives in their treatments. Inflammatory bowel disease (IBD), liver fibrosis, gastrointestinal cancers are the examples that cell therapy and immunotherapy were applied in their treatment, therefore, the cell products like exosomes are the beneficial option in their treatment even cancers with promising results in animal models.
7 Exosomes in GI Diseases: Abstract (con t) Additionally, exosomes role as therapeutic reagents mainly mesenchymal stem cells and dendritic cell derived exosomes in different studies have been under intense investigation and even they are being studied in different clinical trials
8 Baghaei K, et al. Exosomes as a novel cell-free therapeutic approach in gastrointestinal diseases. J Cell Physiol. 2018;1 17.
9 Review of Literature Asseman C, et al Control of experimental inflammatory bowel disease by Regulatory T cells. American Journal of Respiratory and Critical Care Medicine, 162(4 Part 2), S185-S189.
10 Review of Literature Wang G-J, et al Thymus exosome-like particles induce regulatory T-cells. Journal of Immunology, 181(8),
11 Review of Literature Gonzalez MA, et al Adipose-derived mesenchymal stem cells alleviate experimental colitis by inhibiting inflammatory and autoimmune responses. Gastroenterology, 136(3):
12 Review of Literature Yang X, et al Exosomes derived from interleukin-10-treated dendritic cells can inhibit trintrobenzene sulfonic acid-induced rat colitis. Scandinavian Journal of Gastroenterology, 45(10),
13 Review of Literature Zhang B, et al Mesenchymal stem cells secrete immunologically active exosomes. Stem Cells and Development, 1-12.
14 Review of Literature Blazquez R, et al Immunomodulatory potential of human adipose mesenchymal stem cells derived exosomes on in vitro stimulated T cells. Frontiers in Immunology, 5:1-9, November.
15 Review of Literature Wang Y, et al Exosomes released by granulocyte myeloid-derived suppressor cells attenuate DDS-induced colitis in mice. Onco Target. 7(13):
16 Review of Literature Chang L, et al Exosomes derived from human menstrual blood-derived stem cells alleviate fulminate hepatic failure. Stem Cell Research and Therapy, 8(1), 9.
17 Review of Literature Mao F, et al Exosomes derived from human umbilical cord mesenchymal stem cell relieve inflammatory bowel disease in mice. BioMed Research International, 1-12.
18 Review of Literature Yang J, et al Extracellular vesicles derived from bone marrow mesenchymal stem cells protect against experimental colitis via attenuating colon inflammation, oxidative stress, and apoptosis. Plos One. 10(10): e
19 Review of Literature Micheilan A, et al Intestinal permeability in inflammatory bowel disease: pathogenesis, clinical evaluation, and therapy of Leaky Gut. Mediators Inflamm, October 5, 2015: Article ID
20 Abstract The pathogenesis of inflammatory bowel disease (IBD) is multifactorial with data suggesting the role of a disturbed interaction between the gut and the intestinal microbiota. A defective mucosal barrier may result in increased intestinal permeability which promotes the exposition to luminal content and triggers an immunological response that promotes intestinal inflammation. IBD patients display several defects in the many specialized components of mucosal barrier, from the mucus layer composition to the adhesion molecules that regulate paracellular permeability.
21 Abstract (Con t) These alterations may represent a primary dysfunction in Crohn's disease, but they may also perpetuate chronic mucosal inflammation in ulcerative colitis. In clinical practice, several studies have documented that changes in intestinal permeability can predict IBD course.
22 Leaky Gut Intestinal Permeability in Inflammatory Bowel Disease: Pathogenesis, Clinical Evaluation, and Therapy of Leaky Gut Mediators Inflamm. 2015;2015:
23 Review of Literature Landry J, et al Tight junctions in inflammatory bowel disease and inflammatory bowel disease associated colorectal cancer. World J Gastr.oenterology, 22(11):3117
24 Review of Literature Awad W, et al Enteric pathogens and their toxin-induced disruption of the intestinal barrier through alteration of the tight junctions in chickens. Toxins, 9(2):60
25 Review of Literature Vrakas S, et al Intestinal bacteria composition and translocation of bacteria in inflammatory bowel disease. Plos One, 12(1): e
26 Case Study: Evaluating Gut Health in IBD
27 Case Study: Evaluating Gut Health in IBD
28 Case Study: Evaluating Gut Health in IBD
29 Case Study: Evaluating Gut Health in IBD
30 Case Study: Evaluating Gut Health in IBD
31 Case Study: Evaluating Beneficial Bacteria
32 Probiotic Supplementation Key Qualities in Probiotics Robust strains that are capable of surviving the harsh journey to the intestines and are able to attach to the intestinal walls, where they can grow and function effectively to support GI health. The survivability of the strains is further assisted by delayed release technology
33 Case Study: Evaluating Beneficial Bacteria
34 Probiotics and IBD Abstract: Introduction of probiotics can balance the aberrant enteric microflora in IBD patients, and reinforce the various lines of intestinal defense by: -inhibiting microbial pathogens growth, -increasing intestinal epithelial tight junction and permeability, -modulating immune response of intestinal epithelia and mucosal immune cells, -secreting antimicrobial products, -decomposing luminal pathogenic antigens. Vrakas S, et al Intestinal bacteria composition and translocation of bacteria in inflammatory bowel disease.plos One, 12(1): e
35 Matthew Langan s Journey of Healing from Crohns/Colitis Previously healthy 31 yo Hospitalization The start of his journey Used with permission of patient
36 Used with permission of patient
37 Inflammatory Bowel Disease: Crohn s Disease
38 Inflammatory Bowel Disease: Crohn s Disease
39 Used with permission of patient
40 Analyzing the terrain BEFORE planting the grass
41 Analyzing the terrain BEFORE planting the grass
42 Complete Blood Count: Eating steak
43 Chemistry Profile
44 Chemistry Profile
45 The Importance of Mucosal Immunity The dominating part of the immune defense, even if flora is excluded, is localized in the gut no less than 75% of the immune cells of the body are suggested to be found in the GI tract. Bengmark S. Acute and "chronic" phase reaction--a mother of disease, ClinNutr, Vol. 23, No. 6, pp , December 2004
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54 Assessing MicroNutrient Deficiencies
55 Evaluation of Intestinal Permeability
56 Evaluation of Food Sensitivities
57 The Journey to Healing: Treatment Plan Replace the building blocks -IV amino acids, vitamins, minerals, lipids -Elemental diet with anti-inflammatories Remove SLOWLY opportunistic pathogens Replace the beneficial bacteria Repair the gut lining -Diet: gluten, dairy, lectin free (for now) -oral supplements to promote healing
58 The Journey to Healing: Treatment Plan Replace the building blocks -IV amino acids, vitamins, minerals, lipids -Elemental diet with anti-inflammatories Remove SLOWLY opportunistic pathogens Replace the beneficial bacteria Repair the gut lining -Diet: gluten, dairy, lectin free (for now) -oral supplements to promote healing
59 The Journey to Healing: Treatment Plan Replace the building blocks -IV amino acids, vitamins, minerals, lipids -Elemental diet with anti-inflammatories Remove SLOWLY opportunistic pathogens Replace the beneficial bacteria Repair the gut lining -Diet: gluten, dairy, lectin free (for now) -oral supplements to promote healing
60 Replacing Beneficial Bacteria
61 The Journey to Healing: Treatment Plan Replace the building blocks -IV amino acids, vitamins, minerals, lipids -Elemental diet with anti-inflammatories Remove SLOWLY opportunistic pathogens Replace the beneficial bacteria Repair the gut lining -Diet: gluten, dairy, lectin free (for now) -oral supplements to promote healing
62 Nutrition to heal the gut
63 The Journey to Healing: Treatment Plan Replace the building blocks -IV amino acids, vitamins, minerals, lipids -Elemental diet with anti-inflammatories Remove SLOWLY opportunistic pathogens Replace the beneficial bacteria Repair the gut lining -Diet: gluten, dairy, lectin free (for now) -oral supplements to promote healing -Peptide: BPC-157 SQ daily 60 days -Peptide: Thymosin Beta 4 SQ daily 60 days
64 Peptide: Body Protective Compound-157
65 Peptide: Thymosin Beta-4 for Healing
66 Matthew: At the beginning of his journey Used with permission of patient
67 Used with permission of patient Matthew: 2.5 months into his journey of healing 7/9/18 99 lbs
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69 Arnold Palmer Golf Course Orlando, FL
70 Present Case Study 45 year old male with progessive Crohn s Disease Refractory to steroids Refractory to numerous biologic medications Refractory to peptide therapy Multiple hospitalizations Refuses to have a total colectomy Undergoing iron infusions for refractory anemia Undergoing IV nutrition to replace nutrients Preparing for treatment with exosomes
71 Review of the Literature Baghaei K, Tokhanbigli S, Asadzadeh H, Nmaki S, Zali MR, Hashemi SM. Exosomes as a novel cell-free therapeutic approach in gastrointestinal diseases. J Cell Physiol. 2018;
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