Nano Plasma Equine Product Fact Sheet What is Nano Plasma Equine? An advancement in platelet rich plasma technology, Nano Plasma Equine is a convenient off the shelf stem cell signaling product designed containing platelet rich plasma lysate (PRL), including platelet microvesicles (exosomes), along with conditioned serum (raised Interleukin-I Receptor Antagonist Protein) in a convenient ready to administer sterile vial. Nu-Vet Biological Division has pioneered a safe innovative regenerative medicine product that assists with pain management in horses, is an ideal treatment therapy for tendon and ligament injuries ensuring competitive horses heal sounder than ever before. Nano Plasma Equine is manufactured using universal donor veterinarian inspected plasma and therefore can be used multiple times without the risk of rejection; in fact Nano Plasma Equine is ‘Cell Free’ making it safe and effective. Nano Plasma is not cryogenically frozen and does not require liquid nitrogen during storage. Manufactured in an Australian Pesticides and Veterinary Medicines Authority (APVMA) approved facility in line with strict international “GMP” standards, Nano Plasma eliminates the need for invasive tissue and blood harvesting treatments with one single ready to use vial. What is Platelet Rich Plasma? (PRP) Platelet Rich Plasma (PRP) is blood plasma in which concentration of platelets is elevated four to eight times than normal blood platelet concentration. PRP is also called platelet rich gel, platelet enriched plasma and platelet enriched gel. PRP contains (and releases through degranulation) several different growth factors and other cytokines that stimulate healing of bone and soft tissue. PRP is an effective treatment to treat various diseases such as orthopedic diseases, neurological diseases and cardiothoracic diseases. What is Allogeneic Conditioned Serum? (ACS) Nano Plasma contains anti-degenerative compounds such as Interleukin-I Receptor Antagonist Protein (IL-1ra). IL-1ra blocks the inflammatory mediator Interleukin-1 from binding to its receptor and triggering an inflammatory response that leads to tissue destruction. Another important component of ACS is Interleukin 10 (IL-10). A recent study of IL-10 validates its usefulness in limiting and ultimately terminating an inflammatory response. What are platelet microvesicles? Much is already known and much still remains to be discovered about the roles played by platelets in human health. Platelets are quantitatively and qualitatively important blood cells that play key roles in hemostasis, and are also critically involved in physiological processes influencing vascular biology, angiogenesis, immunity, and tissue regeneration. Platelets are sensitive health markers that are prone to activation under physiological conditions involving stimulation of blood coagulation, as occurs as a result of trauma. Therefore, platelets fulfill wide roles in balancing health and disease. It is well established that platelets play a major role in tissue repair, vascular remodeling, and organ regeneration, in particular due to their content of bioactive substances entrapped within α-granules, dense granules, and lysosomal granules, or present in the cytoplasm. Platelets α-granules contain a myriad of growth factors which orchestrate tissue regeneration, including platelet-derived growth factor (PDGF), TGF-β1, VEGF, epithelial growth factor (EGF), brain-derived neurotrophic factor (BDNF), etc. Platelet growth factor-rich preparations are increasingly used in clinics for the healing of soft and hard tissues, e.g., in treating large recalcitrant ulcers, and promoting bone augmentation in oral-maxillofacial surgery and plastic surgery. NU-VET PTY LTD. ABN: 18600617 PO BOX 5228 Cranbourne Victoria Australia 3977 WEB www.nu-vet.com 1 Cellular microparticles (MPs) are fragments shed from plasma membranes of virtually all cell types that are undergoing apoptosis or are being subjected to various types of stimulation or stress. They are distinct from exosomes, which are shed from intracellular membranes. In general, they are collectively referred to as microvesicles (MVs). Several types of MVs, with a heterozygous size estimated to range from approximately 0.10 µm (100 nm) to 1 µm, circulate in the blood at an estimated concentration of 5–50 µg/ml. These MPs are circulating phospholipid (PPL)-enclosed vesicles that originate from either endothelial cells, erythrocytes, leukocytes, megakaryocytes, or platelets. The roles that platelet MVs (PMVs), previously known as “platelet dust”, play in complementing the various physiological functions of platelets are the subject of active research and clinical interest at Nu-Vet Biologics. In vivo, PMVs can be released from platelets under normal physiological conditions or as a result of activation, stress, or apoptosis. From a study of surface markers, PMVs are probably the most abundant MVs in healthy subjects, accounting for 70%–90% of those circulating in the blood [8], with a range of approximately 100–1000/µL. The remaining MVs are released by endothelial cells, leucocytes, and red blood cells. As PMVs can express functional receptors from platelet membranes and are platelet-based nanoparticles, they are increasingly regarded as being instrumental in platelet–cell and cell–cell communication. They contain bioactive molecules capable of transferring messages to neighboring or target cells. As such, PMVs can potentially be a benefit to the cellular environment in a wound that is interacting with the blood vasculature as they expose a procoagulant platelet surface and act as a conveyer of a range of bioactive molecules, including growth factors and other signaling molecules, and genetic materials, including miRNAs. Whereas PMVs can amplify the actions of activated platelets and may have beneficial effects in enhancing vascular tissue repair and regeneration. PMVs may have a function in development, angiogenesis, wound healing, and more generally in tissue remodeling, possibly acting as naturally occurring liposome-like structures able to serve as delivery carriers of growth factors to damaged cells and tissues. PMPs can indeed play a positive role in endothelium tissue repair. The addition of PMVs to endothelial outgrowth cells (EOCs) enhanced their endothelial regeneration capacity in vivo by enhancing EOC recruitment, migration, differentiation, and release of proangiogenic factors. PMVs may also induce the transformation of peripheral blood monocytes into endothelial progenitor cells, with possible implications for cardiovascular research. The constant presence of PMVs in the bloodstream has a physiologically significant contribution to maintaining the function of a healthy endothelium. PMVs may also play a role in the repair of myocardial muscle as intramyocardial injections induce a marked increase in the amount of new capillaries following ischemia. Injection of PMVs has also been proposed to enhance the effects of therapeutic angiogenesis for limb ischemia in atherosclerotic patients. Local application of PMVs, that contain cytokines and growth factors that influence angiogenesis, may emerge as a novel therapeutic strategy for targeting angiogenesis-related conditions. The regenerative role of PMVs on hard tissue is suggested by a study showing that PMVs accelerate bone regeneration in grafting applications, as evidenced by a 20 ~ 50-fold increased mitogenic response of human trabecular bone-derived cells, thereby contributing to the regeneration of mineralized tissue. PMVs may also promote neuronal cell proliferation, survival, and differentiation, suggesting a role in treating brain injuries. PMVs can be internalized by brain endothelial cells in vitro, and can modify their phenotype and functions. PMVs, which promote all stages of angiogenesis in vivo, in addition to procoagulant and inflammatory effects, are capable of improving reperfusion in a rat myocardial infarction model. Moreover, incubation with PMVs in vitro increases angiogenesis and the survival, proliferation, and differentiation of neural stem cells. Interestingly, these effects were also shown in an in vivo model of cerebral ischemia where PMVs were topically applied to the injured brain using a biodegradable polymer. Finally, the therapeutic target of PMVs could be also activated before being injected in order to promote neuronal cell survival, as recently demonstrated in a rat model of brain ischemia by middle cerebral artery occlusion. NU-VET PTY LTD. ABN: 18600617 PO BOX 5228 Cranbourne Victoria Australia 3977 WEB www.nu-vet.com 2 What benefits/ advantages does Nano Plasma Equine have? - Incite vascularization An immune-modulatory/anti-inflammatory effect Stimulate tissue regeneration Improve the function of cells in the joint Recruit other cells to the site of the injury Prevent cell death Nano Plasma is manufactured on a large scale and not subject to the batch-to-batch variations – as sometimes seen in the production of adipose derived or donor stem cells. Nano Plasma is manufactured using a clearly defined/characterised/reproducible specification. Each batch is independently verified to contain a minimum reproduced standard per batch. Only ‘Cell-Free” plasma is injected into the patient making re-dosing possible. Minimal invasive procedure – does not require tissue or blood extraction from the patient. Nano Plasma has a short procedural time (minimally-invasive) for both the veterinarian and patient making it a more convenient treatment. Unlike most allogeneic cell therapies, Nano Plasma is not cryogenically frozen or stored in liquid nitrogen. This would make Nano Plasma readily accessible for use. Theorized Mechanism of Action: Nano Plasma works by signaling the animal’s inherent stem cells in vivo. Nano Plasma’s rich source of nutrients, growth factors, cytokines and microvesicles is all contained in PRL after conditioning the serum. When injected intravenously, intramuscularly or Intra articular Nano Plasma is distributed systemically or regionally and subsequently activates the animal’s inherent and regional regenerative cells in vivo. This action produces a regenerative effect and has resulting improvements in the overall health, recovery and well being of the animal. Not Just Another Blood or Cell Product! Nu-Vet’s personnel have been involved in stem cell products and research for over 10 years developing in depth knowledge about stem cells and how they work. Using our Knowledge in this field Nu-Vet has created Nano Plasma an innovative new stem cell signaling product. Does Nano Plasma Have Any Side Effects? To date Nano Plasma Equine has had no side effects and or adverse reactions when used in accordance with the directions for use. Nano Plasma Equine uses only veterinarian inspected and approved universal plasma that has been obtained from APVMA approved facilities in Australia. Is It Legal For Performance Animals? Nano Plasma Equine (used in accordance with the directions for use) contains no banned substances and does not swab. Rules of racing must be observed in each respective country. Sizes & Availability? Nano Plasma comes in a convenient 2ml sterilised vial. 0.5ml is used for Intra - articular injections. Administration: A veterinary practitioner can give a bolus intravenous (IV) intra-articular or intramuscular (IM) injection. Storage: Vials should be stored in a refrigerator at 4°C - 8°C. Do not freeze. Do not expose to sunlight. Keep out of reach of children. Nano Plasma Equine is not cryogenically frozen and does not require liquid nitrogen during storage. NU-VET PTY LTD. ABN: 18600617 PO BOX 5228 Cranbourne Victoria Australia 3977 WEB www.nu-vet.com 3 For further information on this product or any NU-VET product please contact the company on the details below. MADE IN AUSTRALIA “Innovation not Imitation” Phone: +61 434535104 or +61 468962685 Email: [email protected] Web: www.nu-vet.com NU-VET PTY LTD. ABN: 18600617 PO BOX 5228 Cranbourne Victoria Australia 3977 WEB www.nu-vet.com 4
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