Anu RHEO™

Amniotic Fluid Matrix Products
Now with Wharton's Jelly

Anu RHEO™2018-11-14T14:27:52+00:00

Introduction to Anu RHEO+™

Anu RHEO+™ amniotic fluid matrix products are aseptically prepared, minimally manipulated human tissue allografts for homologous use.  Anu RHEO+™ is intended to supplement or replace damaged or inadequate connective tissue. Amniotic fluid is the clear to slightly yellowish fluid that surrounds a baby in the uterus.  It acts as cushion against hard blows to protect the baby and also helps to regulate the temperature as well. Amniotic fluid is a rich source of nutrients, cytokines, and growth factors that are required for fetal development and maturation.

The new RHEO+™ contains Wharton’s jelly; a mucous tissue within the umbilical cord that protects and insulates blood cells made from mucopolysaccharides such as hyaluronic acid and chondroitin sulfate. The MSC ‘s within Wharton’s jelly consist of functional myofibroblasts that can be isolated with minimal manipulation of the tissue, easily preserving their natural anti-inflammatory and pro-regenerative ability without complication or deterioration.

Anu RHEO+™ is a perfect match for synovial fluid in joints and exhibits anti-scarring and anti-adhesion in addition to anti-inflammatory properties.

Advantages of Anu RHEO+™ Over Corticoid Steroid Injections

Corticosteroid injections have been used for a very long time. Their anti-inflammatory and pain relief properties have made its use a common practice within the medical community. Corticosteroid injections have been shown to be effective in decreasing the inflammation and pain of ligament injuries for up to 8 weeks; however, these same properties lead to destruction of cartilage as mentioned above. Simply, the body heals via inflammation, cortisone inhibits inflammation and healing by disrupting the three characteristic phases: inflammatory, proliferative and remodeling.

Amniotic fluid has very similar characteristics to the synovial fluid that is present in the joints.  The natural lubrication and anti-inflammatory properties help to create an ideal environment for your body to help the proliferation and remodeling of the damaged tissue via the native stem cells present in the body.

Rheo Plus™ comes in 1cc and 2cc

What Are the Clinical Benefits?

Typically used for minimally invasive treatment of damaged or inadequate tissue. Amniotic fluid (AF) possesses anti-inflammatory, anti-microbial and regenerative properties that make it attractive for use in clinical applications.

Why Would Physicians Be Interested?

Anu RHEO+™ amniotic fluid matrix products with Wharton’s Jelly provide the extracellular matrix needed for the infiltration, attachment and proliferation of cells required for the repair of damaged tissue.  Amniotic fluid may reduce scarring, fibrosis, and adhesions in surgical and wound sites.  It may also promote tissue regeneration by providing an anti-microbial and anti-inflammatory environment at surgical and wound sites.

Benefits of a High Quality Allograft Versus Bone Marrow or Adipose Tissue

  • High proliferative capacity and an abundant supply of live mesenchymal stem cells

  • Trilineage differentiation ability  – ectoderm, mesoderm, and endoderm

  • Can differentiate into adipogenic, osteogenic, chondrogenic, and neural cells

  • Provokes little immune response when transplanted, cell rejection is not an issue and human leukocyte antigen (HLA) matching is not necessary

  • Immunomodulatory properties –

    • Cells do not pose risk for metastasis of tumor cells
    • Cells promote proteins that halt the cell cycle of cancer cells and promote tumor suppressing genes
    • Cells invoke the body’s immune system
  • Induce hepatocyte differentiation

  • Can differentiate into Schwann cells

  • Help organize tendon collagen fibers

  • Noninvasive procedures such as liposuction or bone marrow collection. Are more robust than other MSC from other sources such as fat. Range and level of specific cytokines that are different from those expressed by adult mesenchymal stem cells

  • Have stronger myogenic potential and engraftment properties

  • Have a stronger anti-inflammatory protective effect

  • Have less damage from reactive oxygen species (ROS)

  • Increased expression of integrin and increased phosphorylation of focal adhesion kinase Src and FAK

  • Lack the damage from NSAIDs improving the cells viability or plasticity

  • Have been shown to differentiate into nervous system cells, liver, pancreas, heart, and other organs of the body

  • Continue to express molecules with immune-modulating activity after they are extracted from    the umbilical cord and able to pass this ability to their progeny This enables the infused donor  cells, whether differentiated or not, to engraft into the diseased target organ and positively modify its microenvironment to promote repopulation the infusion of immunomodulatory MSC provide a significant advantage by better overcoming host responses, providing the needed  functional bridging action, and modifying the underlying pathological conditions at the basis of disease

  • Retain telomere at the highest possible length which protects them from premature loss of viability

  • Larger amount of different growth factors especially bFGF

  • Strong migratory ability toward the site of inflammation

Frequently Asked Questions

Where will the product be recovered from?
The birth tissues are recovered from hospitals in Northern Florida, Alabama, Tennessee and North Carolina.
What hospital?
Various JCAHO (Joint Commission on Accreditation of Healthcare Organizations) accredited hospitals are used for collection. We have contracted with AATB accredited companies that have protocols in place, to collect placental tissues during elective C-section deliveries and provide all interviewing, collection and maternal testing.
How far is it from the processing facility?
Processing facility is in Florida. Donated tissue is shipped priority overnight via FedEx or delivered via controlled carrier.
Will a company representative be always present to immediately receive and properly transport the product immediately upon recovery?
Yes, all deliveries are tracked to ensure that donated tissue is taken care of upon delivery. Every step is documented from mother’s decision to donate to final delivery to recipient. The collection times and processing times are coordinated to reduce the interval time from delivery to processing.
What are the standards for donation? How are the candidates screened and tested pre-delivery?
All candidates undergo an interview by a trained nurse to assess physical appearance, behavioral risk (tattoos, travel, sexual activity, etc.), and maternal health history. All donated tissues are accompanied by a maternal blood test which tests for HIV, HTLV, CMV, Hepatitis A and B, Syphilis.
Aseptic, scheduled, cesarean section only?
Yes.
Does the product contain any chorion and what is the product tested for prior to processing?
Our Anu RHEO™ Tissue product is the only product that is offered that comes from amniotic membrane.  All chorionic membrane is dissected away during the first steps of processing.  Tissues are tested for bacterial and fungal contamination at the time of collection.
Chain of custody? From recovery-transport-storage-testing-processing-manufactuing-storage and shipping…does the company maintain control through the entire process and handle EVERYTHING?
Chain of custody is closely monitored from the time the mother decides to donate until the final product is used. The company procures the tissue and carefully labels all containers and paperwork. They package the material and deliver to FedEx where tracking information is obtained and the tissue is carefully followed until it is delivered into Anu Life Sciences staff prior to 10 am the next day. Paperwork follows the tissue through the check-in process, all processing steps, and storage and shipping steps. In addition, all samples are tracked after shipping as well. We are required to track the sample through injection and afterward in case of adverse effects. Anu Life Sciences follows all FDA, AATB, AABB standards, quality system developed with the goal of becoming ISO 13485 compliant, sampling of all processed tissue per USP 71 standards.
Does the product contain any chorion and what is the product tested for prior to processing?
Our Anu RHEO™ Tissue product is the only product that is offered that comes from amniotic membrane.  All chorionic membrane is dissected away during the first steps of processing.  Tissues are tested for bacterial and fungal contamination at the time of collection.
What is the current FDA status and compliance with the new guidelines?
Presently we are minimally manipulated and full under FDA 361. We are preparing for potential new guidelines and rules to be issued by the FDA in the foreseeable future. In anticipation of these rule changes, Anu life sciences is compiling data to submit multiple IND applications for a variety of studies utilizing our allografts.  We don’t know if the FDA will decide placental allografts need to be classified as a drug. At that point, then we would pursue FDA 351 approval. The FDA may decide that we need to only show safety and efficacy. Somewhere in between those two options will lie the decision of the FDA and we intend to be fully compliant with their decisions.
Where are we with these new regulations and are we currently in compliance?
Under the new, proposed guidelines, our Anu RHEO™ Tissue products are compliant. Our future allograft product might need to undergo some procedural changes to remain compliant. No matter which path the FDA chooses for placental tissue allografts, we are dedicated and determined to collect all objective and subjective data that we can, and insure that the data is compiled and published in a timely manner.
Have we received a warning letter and if so what action was taken?
No warning letters.
Any adverse reports?
None.
Rejections?
None.
Further information about the products, micronized vs. moralized?
Amniotic membrane is cryofractured, no micronization or morselization.
What sizes of flowable Allograft are available?
1 and 2mL sizes in Anu RHEO™
Freezer program- are we willing to provide -80 degree Celsius cryopreservation system that utilizes liquid nitrogen?
At present we have a liquid nitrogen storage program available for our clients.
Shelf life?
Anu RHEO™ freezer life is 2 years.
Packaged product shipped from their facility to customer 24, 36, 96 hours?
Priority overnight, within 24 hours.  Packaging will maintain -80 degree Celsius for 72 hours.
Properly stored product in a -80 degree Celsius?
Anu RHEO™ properly stored at -80 degree Celsius will last at least 2-3 years. ReGen Anu RHEO™ in liquid nitrogen will last indefinitely.
Who is the lead scientific director?
Dr. Bruce Werber is the lead Scientific Director and the Medical Director.
Is it FDA approved?
YES it falls under the minimally manipulated tissue protocol.
Is it covered by insurance?
Some procedures maybe covered we are working on getting those CPT codes and payments worked out.
What is the COST?
Pricing is available upon request.
What is the efficacy?
Peer reviewed studies have established that the use of minimally manipulated allograft suspension has significant effects on damaged tissue. Please refer to References to Published Studies.
Will we receive training?
We have doctors on standby that can assist your clinic in how procedures are to be done.  We will also in the future put on training sessions for prospective physicians.
What sort of procedures utilize Predictive’s allograft products?
Currently our allograft tissue products are used in a variety of clinical settings. Wound management/ulcers and orthopedic and sports medicine applications.
Can I get a sample order?
Sample orders are not sent out, but if you are interested in utilizing our products for your next procedure we can provide a single dose at a reduced rate.
What steps do we have to take after receiving the products?
All products come with a donor card that needs to be filled out and sent back to MedGenerex.  Instructions for thawing and storing will be placed in every package.
Are the products covered by product liability?
Products have been approved for liability insurance.
How do I thaw the products once I receive them frozen?
There will be thawing instructions placed into each package.
Who do I place the orders with?
All orders should be placed with your sales representative.  Please include date and time for the procedure.
How will you help me market my practice?
Our partnership clinics will be put into a database where the general public will be able to search for a physician that utilizes Anu RHEO™ allograft membrane.  We will also be highlighting various clinics and also being doing local promotions for the doctors.  Details will be worked out with you and your account representative.
What is the current market rate for stem cell procedures?
Current market prices for regenerative medicine procedures range anywhere from $4000 to $30,000 depending on the procedure.  Most procedures involving stem cells are utilizing autologous stem cells procured through adipose or bone marrow.
How many MSC can I expect per cc?
Average viable MSCs that are in our Anu RHEO™ ranges from 400K to 1.2 Million per cc.
Why should I transition over to Anu RHEO™ and discontinue my adipose or bone marrow stem cell?
The shortened procedural time and more potent product gives the patient a clear advantage over the use of the aged and often ineffective MSC from adipose tissue. Reduces recovery period as the patient does not have to schedule for the adipose or bone marrow removal. Please see key points for more benefits of  Anu RHEO™.
What sort of product support will I receive for my practice?
All offices will be able to reach our representative at any time of the day.
What do I do with the patient outcome reports?
Patient follow up information and progression may be asked for by MedGenerex representatives to help with outcome data.
Can I use your Anu RHEO™ for other type of procedures?
Currently our Anu RHEO™ has been specifically developed for orthopedic and surgical applications.  We make no claims on the use of the product for diseases or the treatment of diseases.  Stem cell therapy is relatively new and any statements regarding the cure of any disease has not been scientifically proven.

Published Studies for the Efficacy of Allograft Tissue Products Derived from Birth Tissue

  1. Batsali, A. Comparative Analysis of Bone Marrow and Wharton’s Jelly Mesenchymal Stem/Stromal Cells. Blood. 2013:122:1212.
  2. Batsali, AK et.al. Mesenchymal stem cells derived from Wharton’s Jelly of the umbilical cord: biological properties and emerging clinical applications. Current Stem Cell Research and Therapeutics. 2-13 Mar: 8(2): 144-55.
  3. DiMarino, A. et.al. Mesenchymal Stem Cells in Tissue Repair. Frontiers in Immunology. 2013;4:201.
  4. Doi, H. et.al. Potency of umbilical cord blood- and Wharton’s jelly-derived mesenchymal stem cells for scarless wound healing. Scientific Reports 6 :18844(2016).
  5. F Gao et.al. Mesenchymal stem cells and immunomodulation: current status and future prospects. Cell Death and Disease (2016) 7, e2062; doi:10.1038/cddis.2015.327.
  6. Hye, J. et.al. Comparative Analysis of Human Mesenchymal Stem Cells from Bone Marrow, Adipose Tissue, and Umbilical Cord Blood as Sources of Cell Therapy. International Journal of Molecular Science 2013 Sep: 14(9): 17986-18001.
  7. Hsieh J-Y, Wang H-W, Chang S-J, Liao K-H, Lee I-H, Lin W-S, et al. (2013) Mesenchymal Stem Cells from Human Umbilical Cord Express Preferentially Secreted Factors Related to Neuroprotection, Neurogenesis, and Angiogenesis. PLoS ONE 8(8): e72604. doi:10.1371/journal.pone.007260
  8. Kalaszczynska, I and Ferdyn, K. Wharton’s Jelly Derived Mesenchymal Stem Cells: Future of Regenerative Medicine? BioMed Research International. Vol 2015 article ID 430847.
  9. Liu, Y. et.al. Therapeutic Potential of Human Umbilical Cord Mesenchymal Stem Cells in the Treatment of Rheumatoid Arthritis. Arthritis Research and Therapeutics. 2010; 12(6): R 210.
  10. Murphy, M. et.al. Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine. Experimental and Molecular Medicine. 2013 Nov; 48(1) e54.
  11. Sobolewski, K. et.al. Wharton’s jelly as a reservoir of peptide growth factors. Placenta. 2005 Nov;26(10):747-52.
  12. Watson, N. et.al. Discarded Wharton’s Jelly of the Human Umbilical Cord: A Viable Source for Mesenchymal Stem Cells. Cytotherapy. 2015 January; 17(1): 18-24.
  13. Ye, B. et.al. Rapid biomimetic mineralization of collagen fibrils and combining with human umbilical cord mesenchymal stem cells for bone defects healing. Material Science and Engineering C Material Biology Appl. 2016 Nov 1, 68: 43-51.
  14. Bellamy, et al. Viscosupplementation for the treatment of osteoarthritis of the knee. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD005321
  15. Didier Demesmin, MD Amniotic Fluid as a Homologue to Synovial Fluid: Interim Analysis of Prospective, Multi-Center Outcome Observational Cohort Registry of Amniotic Fluid Treatment for Osteoarthritis of the Knee Presented at the 2015 AAPM Annual Meeting
  16. Brohlin, et. al, Characterisation of human mesenchymal stem cells following differentiation into Schwann cell-like cells. Neuroscience Research. 2009, 64(1):41-49.
  17. Chaudhury, S. Mesenchymal stem cell applications to tendon healing. Muscles Ligaments Tendons J. 2012 Jul-Sep; 2(3): 222–229.
  18. Udalamaththa, V. et.al. Potential Role of Herbal Remedies in Stem Cell Therapy: Proliferation and Differentiation of Human Mesenchymal Stromal Cells Stem Cell Research and Therapy. (2016) 7:110.
  19. Aleynik , et. al. Stem cell delivery of therapies for brain disorders. Clinical and Translational Medicine 2014, 3:24
  20. Li, et. al, Comparative analysis of human mesenchymal stem cells from bone marrow and adipose tissue under xeno-free conditions for cell therapy. Stem Cell Res Ther. 2015; 6(1): 55.
  21. Anzalone R, et al. Wharton’s jelly mesenchymal stem cells as candidates for beta cells regeneration: extending the differentiation and immunomodulatory benefits of adult mesenchymal stem cells for the treatment of type 1 diabetes. Stem Cell Rev. 2011; 7(2):342-63.
  22. Tesche LJ, Gerber DA. Tissue-derived stem and progenitor cells. Stem Cells International. 2010; 2010:824876.
  23. Kalaszczynska, et. al, Wharton’s Jelly Derived Mesenchymal Stem Cells: Future of Regenerative Medicine? Recent Findings and Clinical Significance. Biomed Res Int. 2015; 2015: 430847

Types of Allografts we offer

Anu RHEO+

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Cord Blood

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EXOSOMES

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Procurement Process

All birth tissue products are obtained from C-section deliveries from normal, full-term pregnancies.  Donors that consent to use of their birth tissues are carefully screened prior to the use of their tissues in manufacturing.

Comprehensive medical and social histories of the donors are obtained and tissues are procured, processed, and tested to minimize potential risks of disease transmission to recipients. Infectious disease testing is performed at a certified laboratory in accordance with the Clinical Laboratory Improvement Amendments of 1988 (CLIA) and 42 CFR part 493.

Each donor is tested for HBsAg  (Hepatitis  B  Surface  Antigen),  HBcAb  (hepatitis  B  core  Antibody), HCV (hepatitis C Antibody), HIV I/II-Ab (Antibody to Human Immunodeficiency Virus Types 1 and Syphilis detection test, HIV NAT (HIV Nucleic Acid Test), and HCV NAT (HCV Nucleic Acid  Test).

All products are tested post-sterilization to demonstrate the absence of bacterial and fungal pathogens and are non-pyrogenic. All testing results are reviewed by the Medical Director of Anu Life Sciences (15491 SW 12th Street, STE 408, Sunrise, FL 33326, 888-963-7881) prior to release of product.