Technologies

Direct Biologics Extracellular Vesicles –
A New Frontier in Regenerative Medicine

What are Extracellular Vesicles (EVs)?

Involved in cell-to-cell communication

Natural signals with no preservatives

Approximately 30nm – 150nm in size

Extracellular Vesicles Contain:

More than 1,000 regulatory proteins

• Anti-inflammatory cytokines
• Angiogenic growth factors
• Matrix regenerative signals
• Tumor suppressor signals
• Inhibitors of apoptosis

Messenger RNA (mRNA) – ON SWITCH

Translated by recipient cells into new proteins that can regulate inflammatory cells and new vessel formation

Micro RNA (miRNA) – OFF SWITCH

May inhibit mRNA of chronic inflammatory cytokines and matrix catabolic enzymes

Extracellular Vesicles Are Not Small Cells

Direct Biologics’ EV products are isolated from human bone marrow mesenchymal stem/ stromal cells (MSCs) and contain growth factors and extracellular vesicles including exosomes.

• They contain paracrine signals that assist with local cell-to-cell communication.
• They provide a wide array of regulatory proteins to stimulate and modulate many processes within the normal healing cascade.
• They are purified using proprietary cGMP processing and are sterile filtered and tested per USP<71> sterility testing.

Why Bone Marrow MSCs?

• Peer reviewed published studies clearly indicate that BM-MSCs have a much higher safety profile and yield higher quality extracellular vesicles that deliver a more favorable profile of signaling factors vs. perinatal derived MSCs
• Bone marrow derived MSCs are a much more characterized cell source.
• Over 63,000 peer reviewed papers have been published on bone marrow derived MSCs vs. up to 1,200 on perinatal derived MSCs.
• Given the reported differences in safety, quality, and efficacy of extracellular vesicles products, it is important for physicians to thoroughly investigate the extracellular vesicles product being considered.

Scientists have found that when sufficient levels of exosomes can be isolated and protected from degradation, treatment with exosomes can reproduce similar biological activity without requiring the addition of MSCs. 

These observations have since prompted the development of extracellular vesicles including exosomes as an entire category of novel therapeutics.

• Extracellular vesicles provide a natural and comprehensive activation of the body’s healing processes by systematically activating the complex array of cell signals required to restore and maintain tissue health. This is the newest generation of naturally bioactive products for regenerative therapies.
  
• Direct Biologics EVs contain paracrine signals that assist with local cell-to-cell communication. They induce changes in nearby cells that create the appropriate healing environment and aid in tissue repair.

Stem and progenitor cells by nature work to heal, repair, and restore the body. In some cases where there is a chronic abnormality, these cells are inhibited by an inflammatory state, work in an unregulated capacity, and fail to replace lost cells. The 1,000+ regulatory proteins, RNAs and other biomolecules found to naturally occur in healthy tissue and in ExoFlo have been shown preclinically to help modulate inflammatory healing processes. This is accomplished by activating and recruiting local cells to revascularize the area and reduce the inflammatory response to allow natural healing.

AmnioWrap Tri-Layer Placental Allografts

AmnioWrap2 and AmnioWrap3 allografts are unique, specially processed placental grafts that provide a protective barrier or covering. They are processed using a proprietary system that preserves the natural components of the placental layers and minimally manipulates the tissue.

The allografts provide the key components found in human placental tissues, including an intact extracellular matrix (ECM), regulatory growth factors and cytokines. These factors create an environment ideal for tissue repair and regeneration.

Clinical & Scientific Publications

Treatment of Idiopathic Pulmonary Fibrosis With an Extracellular Vesicle Isolate Product
International Journal of Science and Research Archive, 2021, 02(02), 231–236

Treatment of Elbow Arthritis with a Bone Marrow derived Mesenchymal Stem Cell Extracellular Vesicle Isolate Product
J Orthop Study Sports Med. 1(1):1-6. 2021 

IRB Approved Pilot Safety Study of an Extracellular Vesicle Isolate Product Evaluating the Treatment of Osteoarthritis in Combat-Related Injuries
Stem Cell Res 2020, 1(2)-11.

Exosomes Derived from Bone Marrow Mesenchymal Stem Cells as Treatment for Severe COVID-19.
Stem Cells & Dev. 2020;29(12):747-754. doi:10.1089/scd.2020.0080

Exosome Origins: Why the Cell Source Matters
Stem Cells Regen Med. 2020; 4(1): 1-4.

The Safety Profile of a Bone Marrow-Derived Mesenchymal Stem Cell Extracellular Vesicle Isolate Product
J of Stem Cell Research, 2020, 6:026

Intra-Articular Injection of an Extracellular Vesicle Isolate to Treat Shoulder Osteoarthritis in an Athlete
J Regen Biol Med. 2020;2(1):1-6.

Intra-Articular Injection of an Extracellular Vesicle Isolate Product to Treat Hip Labral Tears
Journal of Regenerative Biology and Medicine
J Regen Biol Med. 2019;1(1):1-6.

Treating Discogenic Pain with Mesenchymal Stem Cell Exosomes: What Is the Biologic Mechanism of Action
Jacobs Journal of Bone Marrow and Stem Cell Research
J J Bone Stem Res 2019; 5(1): 017

INTRA-ARTICULAR INJECTION OF AN EXTRACELLULAR VESICLE ISOLATE PRODUCT TO TREAT HIP OSTEOARTHRITIS
International Journal of Recent Scientific Research Vol. 10, Issue, 12(A), pp. 36230-36232, December, 2019

Can IV Infusions Of Bone Marrow Derived Mesenchymal Stem Cell Extracellular Vesicles Be The Fountain Of Youth?
Journal of Regenerative Biology and Medicine, Volume 1; Issue 2 (2019)

Current knowledge on exosome biogenesis and release description
Cell. Mol. Life Sci. (2018) 75:193–208

Exosomes Derived from Mesenchymal Stem Cells
Int. J. Mol. Sci. 2014, 15, 4142-4157; doi:10.3390/ijms15034142

Extracellular vesicles potential roles in regenerative medicine
published: 03 December 2014 doi: 10.3389/fimmu.2014.00608

Investigation of Content Stoichiometry Neural stem cells
PLOS ONE | DOI:10.1371/journal.pone.0146353 January 11, 2016

Wound healing effect of adipose-derived stem cells A critical role of secretory factors on human dermal fibroblasts
Journal of Dermatological Science (2007) 48, 15—24

Concise Review: MSC-Derived Exosomes for Cell-Free Therapy
Stem Cells 2017;35:851–858

Mesenchymal Stem Cell Derived Secretome and Extracellular Vesicles for Acute Lung Injury and Other Inflammatory Lung Diseases
Expert Opin Biol Ther . 2016 July ; 16(7): 859–871.

Paracrine Effects and Heterogeneity of Marrow-Derived Stem/Progenitor Cells: Relevance for the Treatment of Respiratory Diseases
Сells Tissues Organs 2013;197:445–473