Essential Knowledge in the Clinical Use of Exosomes

15 HOUR COURSE (11.75 AMA PRA CATEGORY 1 CME CREDITS*)

CME Certification:
Essential Knowledge in the Science and Potential of Exosomes for Age Management Medicine

The use of Exosomes has experienced exponential growth over the past 5 years. Their uses range from impacting pain management, cardiovascular disease, autoimmune disease, neurodegenerative conditions, cancer therapeutics to treatments for conditions of aging such as aesthetics, hair restoration, orthopedics and sexual function.  AMMG has an educational mandate to fill knowledge gaps for physicians and healthcare professionals. This course is a focused track on Essential Knowledge in the Science and Potential of Exosomes for Age Management including a final examination for Certification.

3-Part Process to complete the Exosomes Certification Course of Study:

  1. Home Study Online - 8.0 CME hrs: Exosomes: The Next Generation of Biologic Medicine - Full Course.
    • Complete at your own pace.
    • The online course is included in the program registration cost. Completion of the online course is a prerequisite to certification.
    • Course Access: After registering you will receive an email with your username and password to access the online course. NOTE: It can take up to 3 days to process.

  2. Live Training at AMMG Conference -3.75 hours of CME Accredited Lectures and 3.25 hrs Non-CME lectures, 7 hrs total: Essential Knowledge in the Science and Potential of Exosomes for Age Management Medicine.
    • This full day live course will be held April 23 at the AMMG Conference in Miami, Florida.

  3. Comprehensive Final Exam: The final exam will be given Immediately following the last lecture at the live course which will be held April 23 at the AMMG Conference in Miami, Florida.
COMPLIANCE DISCLOSURE: AMMG has made every effort to have all lectures and statements made regarding Exosomes comply with all FDA and State and Local laws. This is a science and knowledge based course, and Exosomes is a new and potentially changing area of medicine. Currently Exosomes can only be used in conjunction with an IRB and we encourage you to frequently check for new policies, laws and rules which may apply to your practice and to strictly adhere to all laws which apply.
*By participating in the AMMG Exosomes Program you will be eligible to earn 11.75 AMA PRA Category 1 Credits. To receive those credits, you must complete all participation requirements as outlined here.
8.0 AMA PRA CATEGORY 1 CME CREDITS

Part 1: online Course Content

You can begin the online study immediately and complete at your own pace. Completion of the online course is a prerequisite.

The Exosomes: The Next Generation of Biologic Medicine – Full Course course is included in the registration cost. After registering you will receive an email from AMMG with your login access to this portion of the Exosomes Course. NOTE: It can take up to 3 days to process.

Our bodies retain a robust ability to repair and regenerate throughout the entire course of our lives. Each and every day our bodies lose millions of cells, which must be constantly replenished from pools of stem cells lest we rapidly expire. Aging, chronic pain and chronic injury result from a progressive increase in the demand for stem cells while we experience a concurrent decline in stem cell availability and function. The symptoms of aging and the causes of pain can be treated with modern therapies derived from younger, allogeneic sources. Umbilical cord blood-derived mononuclear cells and MSC-derived exosomes are a potent source of regenerative proteins and RNAs. They can be administered therapeutically in an off-the-shelf manner due to their immune privileged state and used effectively as a flowable allograft without pathological rejection. As we continue to develop these new perinatal products it is important to understand the foundational biology of these cells in order to innovate and utilize their potential in the safest and most effective ways.

Ian White, Ph.D.

Exosomes are small membranous entities of endocytic origin. Their production by a wide variety of cells in eukaryotes implicates their roles in the execution of essential processes, especially cellular communication. Exosomes are secreted under both physiological and pathophysiological conditions, and their actions on neighboring and distant cells lead to the modulations of cellular behaviors. The characterization of exosomes, provides information on aberrant processes, and thus, exosome analysis has many clinical applications. Because they are associated with the transport of different cellular entities across the blood-brain barrier (BBB), exosomes might be useful for delivering drugs and other therapeutic molecules to brain. We will look at exosomes in the literature and review the roles exosomes play in different neurodegenerative diseases.

Kathy O’Neil Smith, M.D.

Lecture begins with a detailed review of the current literature regarding exosomes and the Cardiovascular system. Then switch gears and discuss how exosomes can be used in your clinical practice. (1) The therapeutic and diagnostic role of exosomes in cardiovascular diseases will be discussed. This will include how exosomes and exosomal miRNAs are involved in cardiovascular protection and repair. Review of the bioactive molecules in exosomes and the various forms of miRNA and their roles in CVD. Exosomes and atherosclerosis, heart failure, cardiac regeneration, cardiomyopathy, their roles as functional CVD biomarkers and in gene therapy. Potential application of exosomes in drug delivery. Understanding the Paracrine Effects Exerted by Exosomes Secreted from Cardiac Cells in Cardiovascular Disease. The potential challenges and future perspectives in the use of exosomes for clinical cardiac applications. Combination therapies using exosomes and peptides in various cardiovascular conditions such as acute coronary syndromes, chronic coronary artery disease, hypertensive cardiovascular disease and congestive heart failure will also be reviewed. (2) I will review a turnkey solution to assist the cardiologist/health care provider in utilizing the technology of Exosomes in their office based medical practice to treat both acute and chronic cardiovascular conditions such as ischemic heart disease, peripheral vascular disease and hypertension. This will include a patient data management tool for your health care environment using a cloud-based system that allows patient data security via HIPAA compliant server, which may be customized to your facility’s unique clinical setting. This solution affords the opportunity to deliver regenerative care using FDA compliant and safe cellular based options to treat unmet patient needs, thus legitimizing regenerative therapies for your clinical practice.

George Shapiro, M.D.

This presentation will include sequential PET brain imaging on a 22-year-old male who lost his ability to speak at age two following a vaccination. He was diagnosed with Autism. He had not been able to speak for 20 years when I began treating him; he is now able to speak somewhat and is starting speech therapy. The sequential PET scans will demonstrate a great visual of the reduction of brain infection. The PET gives a computerized calculation via numerical values that validate the increased brain activity in specific brain regions. Most of the time, the same multiple factors are the causation of both premature dementia and Autistic Spectrum disorders.

Marvin Sponaugle, M.D.

Present state of erectile dysfuntion treatment. Extracorporeal low-intensity shock wave therapy, PRP, stem cells, Exosomes. Benefits and risks. How do Exosomes benefit the patients with ED, and Peyrones benefits and risks.

Paul Thompson, M.D.

Recent discoveries have newly revealed that almost all types of cells produce extracellular vehicles (EVs) to communicate with each other. One type of EV, exosomes, transport cargo that regulates cell processes such as the production of protein. The cargo may differ based on the cell of origin, but can include molecules such as messenger RNA, microRNA, membrane proteins, etc. Scientific excitement is rapidly increasing over the promising ability application of exosomes for diagnostic, therapeutic, and regenerative purposes. This presentation will explain exosomes, identify the areas of greatest potential use, and explain how exosomes can facilitate healing and boost cancer immunity following Focal Laser Ablation (FLA) for the treatment of prostate cancer.

Daniel Sperling, M.D.

The Stem Cell Ophthalmology Treatment Study (SCOTS) is the largest ophthalmology stem cell study registered with the National Institutes of Health – www.clinicaltrials.gov Identifier NCT 01920867. SCOTS is Institutional Review Board (IRB) approved and utilizes autologous bone marrow derived stem cells (BMSC) in the treatment of optic nerve and retinal diseases. SCOTS is an open label, non-randomized, efficacy study. There is no placebo or sham arm. All patients meeting eligibility criteria and enrolled in the study receive active treatment. Bone Marrow aspirated from the posterior Iliac Crest is separated to provide Bone Marrow Derived Stem Cells (BMSC) within the stem cell concentrate. The treatment protocols in SCOTS have been continued in the Stem Cell Ophthalmology Treatment Study II (SCOTS 2) also IRB approved and registered with NIH Identifier NCT 03011541.

Jeffrey Weiss, M.D.

The American Cancer Society predicts that the global burden of cancer will be 26.1 million new cancer cases per year and 13 million annual deaths by 2030, up from and 13.2 million cases and 8.2 million deaths in 2013. Unfortunately there is no early detection test for cancer. In the past decade there has been an explosion on the research of exosomes and cancer. Exosomes have a role in cancer in regards to promotion of tumor growth, tumorigenesis, tumor angiogenesis, tumor immune escape, drug resistance, and metastasis. In addition exosomes have a role for a cancer biomarker and may become the standard for early detection or surveillance marker for cancer. Finally exosomes have a role in the future as a cancer therapeutic agent.

Edwin Lee, M.D.

The incidence of Gastrointestinal Diseases, including Crohn’s Disease and Ulcerative Colitis, is growing at an epidemic rate. The mainstay of present treatment includes high dose steroids and if not effective, the addition of “immune-modulating” medications including biologics that decrease the overall immune system and carry an increased risk for early onset cancer. In many cases, this treatment is not effective and the person has to resort to the removal of part of or their entire colon, altering their life forever. Research in the area of exosomes has clarified that these “non cell vesicles” have a beneficial biologic and physiologic function in immune-regulation and inflammation in the autoimmune process. Although there remains to be seen major studies published in the use of exosomes in specifically Inflammatory Bowel Disease (IBD), much research has been carried out in the animal model for IBD, also in human studies regarding autoimmune diseases. This presentation will review the literature of the beneficial outcomes from the use of exosomes in IBD and autoimmunity and how this knowledge can be applied to the treatment of IBD refractory to other treatment options.

Rebecca Murray, APRN, FNP-BC, CDE

Recent evidence shows that part of the regenerative potential of stem cells are due to exosomes and their potential for healing through cell to cell communication, regulating inflammation and immune response. A number of case presentations using exosomes with platelet rich plasma for erectile dysfunction, post stroke and other clinical challenges will be presented.

Michale “Mickey” Barber, M.D.

Dr. Shapiro and Dr. Knapp will take opposing sides in a discussion of what medical technology and / or clinical use is better that of Exosomes or Stem Cells. Each faculty member will present a short oral argument supporting their side and then take part in an unscripted oral discussion with each other and members of the audience.

George Shapiro, M.D & William Kapp III, M.D., MS, FAAOS

Exosomes and their applications represent the newest frontier in clinical medicine. This session will explore the historical discovery of exosomes, how and where they are generated. Early clinical results for treatment of osteoarthritis, pain, hair restoration, COPD, CHF, pulmonary artery hypertension and age related decline will be presented. Future directions for exosome clinical applications will discuss the status of current IRB studies and opportunities for interested clinicians to collaborate to advance the science of exosome treatments.

William Kapp III, M.D., MS, FAAOS

 

Cells derived from the postpartum placenta have a set of unique biological properties that promise to expand the scope and utility of allogeneic cell therapies in cancer and immunological disease. Celularity’s IMPACT™ platform uniquely accelerates the clinical development of allogeneic cell therapies, the scalability and affordability of which is a function of a near-limitless supply of eligible donor placentas. In immuno-oncology, placental-drived NK cells (PNK) demonstrate intrinsic cytotoxic activity in tumor cells without alloimmune (GvHD) or autoimmune toxicities. Celularity’s PNK-007 product has demonstrated therapeutic promise and promising safety signals in AML and multiple myeloma.

This lecture may contain a commercial aspect and should not be considered as a component of CME, please do not evaluate as such.

Robert Hariri, M.D., Ph.D.

 

3.75 hours of CME Accredited Lectures and 3.25 hrs Non-CME lectures, 7 hrs total

Part 2: Live Training curriculum

This full day live course will be held April 23 at the AMMG Conference in Miami, Florida.

The presence of vesicles outside cells was first identified 50 years ago and were originally thought to be waste products released via shedding of the plasma membrane. It was not until 1987 that the term ‘exosome’ was coined for these extracellular vesicles (EVs) and the endocytic origin was established. Exosomes are unique from other extracellular vesicles not only due to their nanoparticle size (50-200nM) but also because of their endosome origin. Larger EVs such as apoptotic bodies (800-5000nm), and cell membrane vesicles (100-1000nm) are formed from outward budding of the cell surface membrane whereas exosomes are formed from within the cell’s early endosome structures and released during exocytosis fusion to the cell membrane. The distinct origin of exosomes promotes the packaging of many endosome associated proteins as well as an array of intracellular proteins and genetic material. Exosomes function as intercellular communication structures that facilitate the transmission of molecules between cells. In this process exosomes transfer proteins, lipids, mRNA, miRNA and DNA to the recipient cells. It is this delivery system that has elucidated exosomes as an ideal carrier for drugs because they are composed of cell membranes and a lipid bilayer that can deliver cargo inside the cells. A number of cell-based therapies have been tested in the clinic as regenerative tools for the prevention and reversal of degenerative disease. Although clinical efficacy has been variable, these tests have interpreted the role of cell derived secretomes and exosomes as a major mechanistic player in clinical effect. Therefore, exosome therapies are now being explored as an alternative therapeutic tool rather than the cells themselves.

Mari Mitrani, M.D., Ph.D.
Co-founder, American Cellular & Anti-Aging Center, Quito, Ecuador
Chief Science Officer and Co-founderOrganicell Regenerative Medicine

 

Regenerative Therapies including stem cells and Exosomes have taken a center stage in the past several years, in order to remain up to date with these new technologies the clinician should have a basic knowledge of the various types of biologic therapies and the sources of those therapies. The current lecture will review and compare autologous vs allogeneic sources and include discussions on platelet rich plasma, adipose and Bone marrow derived cells, perinatal sources such as amnion, chorion, cord blood and placental tissue. Autologous stem cell treatments traditionally have not been a consistent treatment on a patient to patient outcome basis, now we can use the secretions of stem cells (Exosomes) as our main focus, increasing their availability, and decreasing the complexity required to incorporate them into practice. Evidence from RCTs will be reviewed along with advantages and disadvantages of each source of regenerative therapy.

George Shapiro, M.D.
Adjunct Assistant Professor Clinical Medicine, New York Medical College, Valhalla, NY
Founding Partner, Cenegenics, New York City
Member, AMMG Conference Planning Committee

Exosomes are being studied extensively in various models of degenerative diseases and are rapidly entering the clinic as novel regenerative therapeutics. Thus, the development of clinical-grade manufacturing procedures to isolate exosomes for therapeutic use is required for the development of potent and safe therapies. There are several bioengineering challenges that need to be overcome to successfully and aseptically isolate clinical sized doses of exosomes. These challenges include the ability to reproducibly quantify, qualify, and characterize the exosome product. As with all other cell therapies, exosomes are complex units that contain a wide variety of proteins and genetic material that participate in a synergistic regenerative effect. Therefore, all components of the exosomes should be analyzed to fully elucidate the drug components. In this lecture, we will discuss the various manufacturing techniques that have been developed to produce exosome products. We will also discuss the molecular techniques that are most often used to characterize the exosome products and qualify the product for clinical use.

 

Michael A. Bellio, Ph.D.
Assistant Scientist, Interdisciplinary Stem Cell Institute, Clinical Research Cell Manufacturing Program, University of Miami Miller School of Medicine, Miami, FL
Laboratory and Lead Scientific Director, Organicell Regenerative Medicine

Medical research studies are a crucial step in developing new medicines and treatments. Exosome Therapy is relatively new and the best way to advance the field is by actively participating in research studies. Due to the many sources of exosomes and varieties of pathologies that they can potentially aid, it’s very important to conduct studies to understand their efficacy. The Institutional Review Board (IRB) is an organization that protects the rights and welfare of human research subjects that are recruited to participate in research conducted under the authority of the institution with which it is affiliated. The IRB is intended to minimize risks to human research subjects by using procedures that are consistent with sound research design and procedures, which may already be performed on subjects for diagnosis or treatment purposes. Under FDA regulations, IRB is an appropriately constituted group that has been formally designated to review and monitor biomedical research involving human subjects. In accordance with FDA regulations, an IRB has the authority to approve or disapprove research. Food and Drug Administration (FDA) approval is needed to bring any new drug to the market. An Investigational New Drug (IND) process serves as the primary mechanism in the process to bring a new drug to the market. An IND requires completion of 3 requirements that include: the details of the study, details of the investigator and the study location, and registering the study in the national database of clinical trials. Federal law requires a drug be approved before it is transported across state lines. An IND is required for:

  1. Studies involving a drug or biologic that is not approved for marketing by the FDA.
  2. Studies involving an approved drug or biologic that is being tested to support a new indication or significant change in labeling of the drug or biologic.
  3. Studies involving an approved drug or biologic that is being used or tested in a new route of administration, new dosage level, or new patient population that may increase the risks (or decrease the acceptability of the risks) of the drug or biologic.

 

Mari Mitrani, M.D., Ph.D.
Co-founder, American Cellular & Anti-Aging Center, Quito, Ecuador
Chief Science Officer and Co-founder, Organicell Regenerative Medicine

Exosomes have an endosomal origin and are released by many different cell types. They subsequently participate in different physiological and/or pathological processes. Depending on their origin, they can alter the fate of recipient cells according to the information transferred. There is a tremendous therapeutic potential of exosomes and their applications represent the newest frontier in clinical medicine. Early clinical research for treatment of osteoarthritis, pain, hair restoration, COPD, CHF, CAD, ED, pulmonary artery hypertension, pulmonary fibrosis, and age-related decline are in progress. Research continues to show a possible role of Extracellular Vesicles in the Diagnosis and Prognosis of Various Diseases. Extracellular vesicles contain partially overlapping contents and shared mechanisms for communication and function. Investigations into a broad variety of diseases—oncologic, cardiometabolic, neurologic, and infectious—support a functional and potentially therapeutic role for extracellular vesicles. The results of additional studies suggest that extracellular vesicles may be useful as biomarkers of disease progression or therapeutic response. Hopes on the regenerative effect of extracellular vesicles extends to several organs. Considering pre-clinical data, extracellular vesicles, especially from mesenchymal stem cells, hold great promises for the regeneration of several organs including heart, lungs, bones, liver, skin, pancreas and kidneys. Scientific protocols that will be implemented in clinical studies utilizing these various sources of perinatal tissue for some of the above conditions will be reviewed. In order to meet the FDA’s standards for safety and efficacy, consent forms explaining the details of the procedure should be reviewed and signed by the patient. In addition, an FDA-issued Investigational New Drug Application (IND) number we be required to be compliant.

George Shapiro M.D.
Adjunct Assistant Professor Clinical Medicine, New York Medical College, Valhalla, NY
Founding Partner, Cenegenics, New York City
Member, AMMG Conference Planning Committee

Exosomes have emerged as nano-sized, mRNA enriched, packets of information that allow cells within a tissue to network and coordinate their “states”. Although the precise physiological and pathological functions are in early stages of discovery, a strong body of evidence indicates their pivotal roles in immune regulation. Exosomes may be involved in inflammatory processes that play a pivotal role in a large number of pathologic states including cancer, inflammatory bowel diseases, diabetes, obesity, rheumatoid arthritis, osteoarthritis, and neurodegenerative diseases. Conversely, these same nano-packet networks can be co-opted to deliver an anti-inflammatory phenotypic agenda – therapeutic cargoes capable of reversing diseases and promoting regeneration. We explore in this lecture the art of engineering exosomes to express novel cargoes and thus fashion powerful anti-inflammatory therapeutics fine-tuned to specific anatomic structures, including our own work in diabetes, MS, Alzheimer’s, and Lyme disease.

 

John Sanderson, M.D.
CEO, XOStem, Irvine, CA

In Regenerative Medicine, the “troika” of cells, signals and scaffolds make up the foundation of what clinicians and scientists have in their toolbox. Leveraging the power of this triad is the goal of physicians looking to influence the form and function of our largest organ, the skin, to accelerate healing as well as halt or reverse the signs of aging, including hair loss.  In cosmetic surgery, redistribution of MSC-rich adipose tissue, primarily to replace lost volume, has been observed to exert additional anti-aging benefits to the overlying skin as well as enhance hair follicles when applied into the scalp. Similar to the research on platelet rich plasma, these observed hair growth effects are often attributed to growth factors which have been recognized in playing a role in the chronobiologic activity of the hair follicle. If the “work” of these MSC cells can be fully derived from the paracrine messages sent via their cellular secretome, including exosomes and the material they contain, the hope is that eventually FDA-approved off-the-shelf products can reproduce these beneficial effects without the need for cumbersome tissue transfer at the bedside. The author will review cellular sources of exosomes, research on exosome contents (including growth factors, cytokines, miRNA) and their presumed effect on hair follicle function, controversies and challenges in exosome purification and quantification, in addition to the latest published and other reports on their effect on hair growth.

Alan J. Bauman, M.D., ABHRS
Founder & Medical Director, Bauman Medical Group, Boca Raton, FL

Exosomes may be described as elegantly packaged and precisely labeled complex molecular cargoes, exported by producing cells for import by consuming cells either near or distant. Epithelial tissues including skin and its appendages are constantly shedding and regenerating, with exosomal biosignals playing a major role in structural integrity (dermis), barrier functions (epidermis) and the maintenance of homeostasis. As progenitor and stem cell populations decline and take on senescent phenotypes, we observe a shift in intercellular biosignaling that correlates with alterations in human physiologic function and appearance. In this lecture we explore aging appearance and age-related dysfunctions and the potential for altering these through exosome cargo “engineering” with an emphasis on integument (skin and its appendages) as both from an aesthetic and therapeutic viewpoint, as well as life cycle functional impairments associated with aging (menopause and andropause) and their sequelae. 

John Sanderson, M.D.
CEO, XOStem, Irvine, CA

George Shapiro, M.D., Mari Mitrani, M.D., Alan Bauman, M.D., John Sanderson, M.D., Michael Bellio, Ph.D.

Various case studies will be presented and discussed for several clinical conditions that would benefit from regenerative therapies.

John Rush, M.D.
Member, AMMG Planning Committee

Part 3: Comprehensive Final Exam

The final exam will be given Immediately following the last lecture at the live course which will be held April 23 at the AMMG Miami, Florida Conference.