physician guide

physician guide

Physician Guide

Table of Contents

1. About NewLife 2. Natural Biologics 3. QualityAssurance 4. NewLife Products 5. Product Preparation 6. Q&A 7. Source Articles

1

About NewLife

New Life Medical Services is an FDA registered and reg- ulated, multi-state licensed tissue bank located near Tampa, Florida. New Life, having decades of combined experience, provides clinicians with the safest and most clinically effective natural biologics products available, while remaining cognizant of the rising cost of health- care. Our Vision Our vision is to progress awareness of natural biologics into a social movement that transforms healthcare, allowing people to preserve and enhance their health to fully enjoy their family, friends, and the fruits of their labor. OurMission Statement New Life Medical Services believes patient care should be offered with trust, dignity, and compassion. Our mission is to work closely with top practitioners to offer innovative products that enhance the body’s natu- ral ability to heal through natural biologics.

www.newliferegen.com

2

Natural Biologics

From the young model to the aging retiree, from the elite athlete to the weekend warrior, to the immune-compromised patient and the patient with other comorbidities, clinicians continue to search for ways to control pain and accelerate the healing process. Utilizing various therapies has proven to have many profound benefits; not the least of which includes overall superior outcomes. Dawning on the horizon of medical advancements, these treatments hold the potent heal- ing potential whose benefits have the power to span disciplines as diverse as hair resto- ration and orthopedics. These therapies harness the power and versatility of the human body to regenerate damaged skin, accelerate healing, reactivate hair follicles, heal wounds and alleviate pain. All of us have heard of the usefulness of stem cell therapy but many are unaware there is so much more to natural biologics than just stem cells. Stem cells, whose outcome is greatly dependent on the age of the patient they are being harvested from, decline with age. (Figure 1) For example, a patient over the age of 55 will have much less viable stem cells than a patient in their twenties, which explains the differ- ence amongst us in the time it takes to heal from an injury. Equally important as stem cells are the “dream team” of components in birth tissues including growth factors, cytokines, proteins, collagens, the list goes on.

(Figure 1)

Natural Biologics

Components

The amount of growth factors, cytokines, hyaluronic acid, cellular components and extracellular vesicles are higher in Wharton’s Jelly compared to other biologics. These components aid in strength, flexibili- ty, cushioning, covering, compress- ibility and response to friction in the body. It also plays a vital role in reducing inflammation. Required for the structure, function and regulation of the body’s tissues and organs, proteins help repair tissues and allow metabolic reactions to occur. Some proteins are chemical messengers between cells, tissues and organs while others provide structure and support.

Naturally present in the body, hyaluronic acid acts as a cushion and lubricant for the joints and other tissues. Hyaluronic acid can be used for various joint disorders and aging among other conditions. It may promote healthier, more supple skin, speed up wound healing and preserve bone strength

Wharton’s Jelly

Hyaluronic Acid

As the most dominant protein found in skin, elastin provides resilience and elasticity to tissues and organs. It is 1000 times more flexible than collagen and one of the body’s most enduring proteins.

Elastin

Proteins

Collagens form a scaffold to provide strength and structure throughout the body delivering a platform for new tissue growth.

A form of cytokine that stimulates movement and plays a crucial role in immunological reactions.

Collagens

Chemokines

These molecules serve as messen- gers between cells, mediating and regulating immunity, inflammation and hematopoiesis. They stimulate the production of blood cells and provide growth and differentiation factions that function in develop- ment, tissue maintenance and repair.

Vital in supporting life’s basic functions, carbohydrates produce and store energy, build macromole- cules, extra proteins and assist in lipid metabolism.

Carbohydrates

Cytokines

The building blocks of proteins, amino acids are vital for protein synthesis, tissue repair and nutrient absorption.

Regulate cell division and cell survival to stimulate the growth of a specific tissue.

Growth Factors

Amino Acids

Natural Biologics

Treatments being utilized, as a stand-alone or com- bined, include birth tissues from amniotic fluid/mem- brane, umbilical cord tissue, umbilical cord Wharton’s Jelly umbilical cord blood, platelet-rich plasma (PRP), adipose derived stem cells (ADSC) and bone marrow aspirate (BMA). (Figure 2 and 3) .

(Figure 2)

Comparison of Stem Cells • Umbilical Cord Tissue from Wharton’s Jelly

yields the highest concentration of allogeneic mesenchymal stem cells.

• Bone Marrow ranged from 1 to 317,400 cells/mL

• Umbilical Cord Tissue ranged 10,000 to 4,700,000 cells/cm * C.T. Vangsness Jr., H. Sternberg, and L. Harris. “Umbilical cord tissue offers the greatest number of harvestable mesenchymal stem cells for research and clinical applications: a literature review of different harvest sites.” Arthroscopy, vol. 31, no. 9, pp. 1836-1843, 2015.

(Figure 3)

Natural Biologics

Natural Biologics are a form of tissue engineering and molecular biology which deals with the "process of replacing, engineering or regenerating human cells, tissues or organs to restore or establish normal function". When injured or invaded by disease, our bodies have the innate response to heal and defend. Harnessing and enhancing the body's own regen- erative powers is a medical practice at the frontier of present-day advancements whose properties may seem miraculous to those who benefit from them. The miracle, however, is the result of scientific exploration that has begun to unlock and utilize the body's extraordi- nary ability to heal and restore itself. Cells are the building blocks of tissue, and tissues are the basic unit of function in the body. Generally, groups of cells make and secrete their own support structures, called the extracellular matrix. This matrix, or scaffold, does more than just support the cells; it also acts as a relay station for various signaling molecules. Thus, cells receive messages from many sources that become available from the local environment. Each signal can start a chain of responses that determine what happens to the cell. Through medical technology we can now understand how individual cells respond to sig- nals, interact with their environment and organize themselves into a healing process. Scaf- folds are created utilizing various natural biologic therapies allowing for the tissue to "self-assemble".

3

QualityAssurance

All protocols followed at New Life Medical Services are in accordance with the Food and Drug Administration (FDA) and the American Association of Tissue Banks (AATB) regulations and standards. Our products are derived from birth tissues taken from carefully screened mothers at the time of a normal birth. Our products do not contain any fetal or embryonic tissue.

Donor EligibilityDetermination Birth Tissue is donated by healthy mothers at the time of a normal birth. Expectant mothers submit their past medical and social history through an intensive and com- plete medical review and prenatal evaluation, including culturing and serological testing, prior to delivery. The recovery is performed by trained technicians utilizing aseptic tech- nique. No harm is brought to the newborn and parents will still have the option of stor- ing the cord blood, if desired.

“The Power of theMother.”

QualityAssurance

Prior to the recovery of birth tissue, stringent guidelines must be met.

Eligibility for tissue donation is based on the following:

Comprehensive social and medical screening of the mother-to-be to include: •No known high risk for HIV or hepatitis •Free from transmissible disease •Free from active malignancy •Free from infection

Each donor is tested* for the following:

•HBsAg (hepatitis B Surface Antigen) •HBcAb (hepatitis B core antibody) •HCV (hepatitis C antibody) •HIV I/II-Ab (antibody to human immunodeficiency virus)

•HIV NAT (HIV Nucleic Acid Test) •HCV NAT (HCV Nucleic Acid Test)

All serologies are performed by a certified Clinical Laboratory Improvement Amend- ment (CLIA) laboratory. All processing is performed in a state-of-the-art cGMP facility following the guidelines of both the FDA and the American Association of Tissue Banks.

Culturing is performed during each step of the processing.

Once tissues are processed, they are sent to a third-party testing facility to ensure sterility (absence of bacterial or fungal pathogens). Products are then placed into a quarantine status until all test results and donor files are reviewed by a licensed Medical Director and tissue is deemed ready for clinical use. *Donors are tested in accordance with the standards established by FDA requirements to minimize potential risk of disease transmission to recipients.

4

NewLife Products

At New Life Medical Services, we are committed to helping improve the quality of lives for those individuals suffering from pain, injuries, aging and sometimes, just from day to day living.

With New Life products, we strive to help people feel better and look better.

+

Sourced from the Wharton’s Jelly of the umbilical cord, Restor+ contains concentrated cytokines, growth factors, collagens, proteins, peptides, extracellular matrix, and numerous other compo- nents needed to helo regenerate tissue. Restor+ may be an ideal choice for individuals who are dealing with various conditions that interfere with their everyday lives, especially those individuals over the age of fifty who, due to the aging process, may have less viable components than a younger person might.

Cytosomes are small, membrane bound extracel- lular vesicles (EVs) released by the developing fetus, placenta, and mother into the amniotic fluid (AF). The AF is procured from consenting healthy, carefully screened, and tested mothers at the time of a scheduled cesarean section. Recovery is performed by tissue banks accredited by the American Association of Tissue Banks (AATB) following the stringent guidelines enforced by the Food and Drug Administration (FDA) and the Center for Disease Control (CDC).

Rexo vesicles are anti-inflammatory particles that aid in cell signaling. They contain nearly three times more growth factors than adult stem cells and influence the growth of target cells. They are a vital regenerative component due to their unique ability to transfer information from cell to cell.

Renyte is an acellular product also derived from the Wharton’s Jelly of the umbilical cord. Containing the same acellular components as Restor, Renyte may be an option for those with less serious injuries or who looking for a more youthful appearance.

www.newliferegen.com

Restor+ is a minimally manipulated allograft, derived from the umbilical cord tissue layer of Wharton’s Jelly and processed to maximize concentration. Restor is for homologous use and is intended to enhance the body’s natural ability to heal.

Product Codes

why

RES-005 RES-010 RES-020

5 million 10 million 20 million

+

RES-050 50 million

Restor works by secreting powerful bioactive molecules. Restor contains a network of concentrated cells, scaffolding proteins, growth factors, cytokines, extracellular matrix and multiple other components needed to enhance the body’s natural ability to heal.

Restor umbilical cord tissues lack MHC-II and are therefore hypo-immunogenic. Consequently, there is minimal risk of an allergic reaction for the recipient. 1 Restor has a strong anti-inflammatory effect reducing the expression of inflammatory cytokines. 2 Restor has a higher proliferation rate when compared to autologous tissue such as adipose or bone marrow.

Restor is less invasive when compared to other forms of regenerative medicine such as bone marrow or adipose tissue extraction; this results in less pain and rehabilitation time for the patient. Restor is recovered from healthy, carefully screened mothers at the time of delivery. All protocols are in accordance with the FDA, AATB, and AABB regulations and standards.

1. Sabapathy V, Sundaram B, VM S Mankuzhy P, Kumar S (@014) “Human Wharton’s Jelly Mesenchymal Stem Cells Plasticity Augments Scar-Free Wound Healing with Hair Growth” PLoS One 9 (4): e93726 doi:10. 137/journal.pone0093726 2. 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.327

Disclaimer: New Life does not make claims that products are a cure for any condition, disease or injury. All statements and opinions provided are for educational and informational purposes only and we do not diagnose or give medical nor legal advice. Individuals interested in regenerative medicine therapy are urged to review all pertinent information and do their own research before choosing to participate in treatments utilizing New Life products.

Restor+ Components

Anti-Inammatory IL-1ra IL-10 HGF

TNF RII TGF ẞ -1

Homeostatic Cytokines

IL-2

IL-7 IL-15 TIMP-2 Lipocalin-2

ANG-1 bFGF BMP-7 TGF ẞ -1 VEGF Growth Factors Wound Healing VEGF TGF ẞ -1 IL-6 PDGF-BB HGF bFGF

ANG-1 FGF-7

( 813 ) 461 - 8100 www. new l i f e r egen . com

Restor Characterization Diego Anguiano, Nelson Jen, RajenNaidoo, KevinKong, Habib Tor

Introduction Regenerative medicine is changing how damaged tissues and organs are treated and present a tremendous treatment opportunity for aging-related diseases and for palliative treatment. Regenerative medicine contains unique components that have the capacity to self-renew and the ability to differentiate into different phenotypes. New Life offers products sourced from cord blood (Recharg) and the Wharton’s Jelly (Restor) of the umbilical cord. The cells are sourced from the byproducts of the birthing process and are not fraught with ethical concerns that come with human embryonic stem cells. There are three overarching types of cells: totipotent, pluripotent, and multipotent. Toti- potent and pluripotent cells are sourced from embryos have the potential to develop into any cell type but are not used for therapy due to ethical and medical concerns. Multipo- tent cells, which include hematopoietic stem cells (HSCs) and mesenchymal stromal cells (MSCs), can differentiate into several different tissue specific cell types and are found in a wide variety of tissues. MSCs are a heterogenous population of multipotent cells found in a variety of tissues including adipose tissue, bone marrow, cord blood, and Wharton’s Jelly. The Gold Stan- dard for characterizing MSCs is through identification of the following in vitro character- istics: plastic adherence; potential to differentiate into osteoblasts, adipocytes, and chondroblasts; expression of CD105, CD73, and CD90 surface markers and a lack of expression CD45, CD34, CD14, CD19 and HLA-DR.1 Wharton’s Jelly components (Restor) and cord blood components (Recharg) possess CD34 positive cells, which represent HSCs. These HSCs and MSCs work synergistically together to create a niche rich in cellular growth. Specifically, MSCs create a microenvi- ronment rich in cytokines and growth factors that promotes hematopoiesis. 2 New Life offers two cellular products: Restor and Recharg. WJ cells are believed to be derived from MSCs that become embedded during embryogenesis, creating a more homogeneous population. 3,5 CBSCs derive their cells from the blood circulating in the umbilical cord and placenta creating a more heterogeneous population of cells that includes HSCs, MSCs, and endothelial progenitor cells (EPCs). 2,4,6

(Continued)

In this study, viability and MSC surface markers were analyzed in Recharg and Restor using a BD FACScan and analyzed using CellQuest Pro Software (n=3). Testing was done by third-party Cytologistics, San Diego CA.

Methods

Cell staining

Immunophenotype analysis by flow cytometry was performed as previously described. 7 Briefly, samples were stored at -80°C and thawed in 37°C water and centrifuged at 350 × g for 5 minutes. Cells were resuspended in flow buffer and distributed to microcentrifuge tubes. Antibodies were added at manufacturer’s suggested concentration. Cells were incu- bated with primary antibody for 60 minutes in the dark at 4°C. Following incubation, the cells were washed with flow buffer, centrifuged at 350 × g for 5 minutes, and buffer was aspirated (repeated for two washes). Cells were resuspended in flow buffer and trans- ferred to appropriate tubes for flow analysis. Samples were analyzed using BD FACScan (excitation: 488nm) with CellQuest Pro Software.

Results

Propidium iodide (PI) staining for cell viability was used to assess Recharg and Restor each from 3 distinct donors. The average viability post-thaw for Recharg and Restor was 78.17% ±0.25 and 66.91% ±3.66 respectively (Table 1). MSC and HSC progenitor CD (cluster of differentiation) marker expression was measured in Recharg and Restor for cell surface markers CD105, CD73, CD90, CD45, CD34, CD14, CD19, and HLA-DR (Table 2). Both Recharg and Restor expressed markers associated with both MSCs (CD105, CD73, CD90) and HSCs (CD34). MSC surface marker expression was higher in Restor compared to Recharg (p