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
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
Crohn s Ds: The Journey of a 2 month hospital stay Used with permission of patient
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;1 17. https://doi.org/10.1002/jcp.27934
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.
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.
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
Baghaei K, et al. Exosomes as a novel cell-free therapeutic approach in gastrointestinal diseases. J Cell Physiol. 2018;1 17.
Review of Literature Asseman C, et al. 2000 Control of experimental inflammatory bowel disease by Regulatory T cells. American Journal of Respiratory and Critical Care Medicine, 162(4 Part 2), S185-S189.
Review of Literature Wang G-J, et al. 2008 Thymus exosome-like particles induce regulatory T-cells. Journal of Immunology, 181(8), 5242-5248.
Review of Literature Gonzalez MA, et al. 2009 Adipose-derived mesenchymal stem cells alleviate experimental colitis by inhibiting inflammatory and autoimmune responses. Gastroenterology, 136(3): 978-89.
Review of Literature Yang X, et al. 2010 Exosomes derived from interleukin-10-treated dendritic cells can inhibit trintrobenzene sulfonic acid-induced rat colitis. Scandinavian Journal of Gastroenterology, 45(10), 1168-1177.
Review of Literature Zhang B, et al. 2014 Mesenchymal stem cells secrete immunologically active exosomes. Stem Cells and Development, 1-12.
Review of Literature Blazquez R, et al. 2014 Immunomodulatory potential of human adipose mesenchymal stem cells derived exosomes on in vitro stimulated T cells. Frontiers in Immunology, 5:1-9, November.
Review of Literature Wang Y, et al. 2016 Exosomes released by granulocyte myeloid-derived suppressor cells attenuate DDS-induced colitis in mice. Onco Target. 7(13):15356-15368.
Review of Literature Chang L, et al. 2017 Exosomes derived from human menstrual blood-derived stem cells alleviate fulminate hepatic failure. Stem Cell Research and Therapy, 8(1), 9.
Review of Literature Mao F, et al. 2017. Exosomes derived from human umbilical cord mesenchymal stem cell relieve inflammatory bowel disease in mice. BioMed Research International, 1-12.
Review of Literature Yang J, et al. 2015 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): e0140551
Review of Literature Micheilan A, et al. 2015 Intestinal permeability in inflammatory bowel disease: pathogenesis, clinical evaluation, and therapy of Leaky Gut. Mediators Inflamm, October 5, 2015: Article ID 628157.
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.
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.
Leaky Gut Intestinal Permeability in Inflammatory Bowel Disease: Pathogenesis, Clinical Evaluation, and Therapy of Leaky Gut Mediators Inflamm. 2015;2015:628157.
Review of Literature Landry J, et al. 2016 Tight junctions in inflammatory bowel disease and inflammatory bowel disease associated colorectal cancer. World J Gastr.oenterology, 22(11):3117
Review of Literature Awad W, et al. 2017 Enteric pathogens and their toxin-induced disruption of the intestinal barrier through alteration of the tight junctions in chickens. Toxins, 9(2):60
Review of Literature Vrakas S, et al. 2017 Intestinal bacteria composition and translocation of bacteria in inflammatory bowel disease. Plos One, 12(1): e0170034
Case Study: Evaluating Gut Health in IBD
Case Study: Evaluating Gut Health in IBD
Case Study: Evaluating Gut Health in IBD
Case Study: Evaluating Gut Health in IBD
Case Study: Evaluating Gut Health in IBD
Case Study: Evaluating Beneficial Bacteria
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
Case Study: Evaluating Beneficial Bacteria
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. 2017 Intestinal bacteria composition and translocation of bacteria in inflammatory bowel disease.plos One, 12(1): e0170034
Matthew Langan s Journey of Healing from Crohns/Colitis Previously healthy 31 yo Hospitalization The start of his journey Used with permission of patient
Used with permission of patient
Inflammatory Bowel Disease: Crohn s Disease
Inflammatory Bowel Disease: Crohn s Disease
Used with permission of patient
Analyzing the terrain BEFORE planting the grass
Analyzing the terrain BEFORE planting the grass
Complete Blood Count: Eating steak
Chemistry Profile
Chemistry Profile
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. 1256-1266, December 2004
Assessing MicroNutrient Deficiencies
Evaluation of Intestinal Permeability
Evaluation of Food Sensitivities
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
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
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
Replacing Beneficial Bacteria
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
Nutrition to heal the gut
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
Peptide: Body Protective Compound-157
Peptide: Thymosin Beta-4 for Healing www.tailormadecompounding.com
Matthew: At the beginning of his journey Used with permission of patient
Used with permission of patient Matthew: 2.5 months into his journey of healing 7/9/18 99 lbs
Arnold Palmer Golf Course Orlando, FL
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
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;1 17. https://doi.org/10.1002/jcp.27934