Platelet Poor Plasma in Regenerative Medicine
Platelet Poor Plasma is a component derived from whole blood and has garnered recent attention in regenerative medicine due to its rich content of growth factors, cytokines, bioactive proteins and exosomes.
How Platelet Poor Plasma is Derived
Platelet Poor Plasma, (PPP) is obtained by the centrifugation of whole blood to separate the specimen into three layers. They are based on their density. The three layers are red blood cells, the buffy coat layer and the plasma. When a thixotropic gel separator layer is used in the tube, the heavy dense red blood cells and most of the leukocytes are trapped below, and the platelet rich plasma is located above the gel separator with the platelet poor plasma on top.
Typically, the platelet rich plasma is used for tissue regeneration and the platelet poor plasma is discarded.
Unique Profile of Platelet Poor Plasma
While platelet rich plasma has been extensively studied with thousands of published articles heralding its efficacy, platelet poor plasma has been an afterthought. However, platelet poor plasma offers a distinct profile of bioactive molecules that are unlike those contained in the platelet rich plasma. These molecules offer adjunctive therapeutic application in wound healing, tissue regeneration and inflammatory modulation.
What’s Inside Platelet Poor Plasma
Platelet Poor Plasma is composed of water, electrolytes, proteins and cellular debris. Key bioactive molecules present in PPP include:
Growth Factors in PPP
These proteins stimulate cellular growth, proliferation and differentiation. Key growth factors contained in platelet poor plasma:
- Insulin Like Growth Factor-1: This growth factor has similar molecular structure to insulin and displays an important role in growth in children and has an anabolic effect in adults. In platelets, IGF-1 is released immediately after tissue injury, promoting tissue repair.
- Hepatocyte Growth Factor: This GF is a potent angiogenic factor that regulates cell growth, motility and morphogenesis. It is secreted by mesenchymal cells and interacts with epithelial and endothelial cells.
Both above reside outside of the alpha granules on the platelets and are therefore concentrated in the platelet poor plasma after centrifugation.
Both are:
- Angiogenesis activators
- Inflammation inhibitors
- Fibrosis inhibitors
- Promote keratinocyte migration
- Support tissue repair and wound healing
Cytokines in Platelet Poor Plasma
These are small proteins that mediate and regulate immunity, inflammation and hematopoiesis. Contained in PPP, cytokines such as interleukins and tumor necrosis factor alpha, modulate inflammation and the immune response.
Bioactive Proteins in Platelet Poor Plasma
These include enzymes and inhibitors that regulate extracellular matrix remodeling and cellular communication.
Other Key Proteins in PPP
- Plasma Proteins: Greater than 300 have been identified including Albumen, Fibrinogen, Alpha-2-Macroglobulin. These function in blood clotting, maintain blood pressure, carrier functions, immunity and pH regulation.
- Coagulation Factors: Such as tissue factor, Factor 1, 2, 4, 5, 7 and vWF. These function in intrinsic and extrinsic coagulation pathways.
- Growth Factors: Such as IGF-1 and HGF, previously discussed. These function in bone growth, glucose transport, muscle production, mitogenesis, cell proliferation and cell growth.
Role of Leukocytes in PPP
Leukocytes can be rich or excluded depending on the platelet rich plasma kit and device used. There are leukocytes in platelet poor plasma to a lesser degree than platelet rich plasma. Regarding the various PRP formulations, neutrophils, lymphocytes, monocytes and macrophages have a significant role in the intrinsic biology of classical wound healing cascades and have an impact on chronic tissue pathologies because of their ability to interact with platelets, immune cells and host defense mechanisms. The role of leukocytes in PRP and PPP as well as their impact on tissue regeneration is widely underestimated and leukocytes should not be excluded.
Critical Components of Platelet Poor Plasma
PPP comprises plasma-based growth factors with active roles in several tissue repair and regeneration processes. IGF-1 and HGF are plasma-based growth factors transported by several plasma proteins and more prevalent in platelet poor plasma than platelet rich plasma. There are five critical components contained in plasma when compared to PRP. These include:
- Hepatocyte Growth Factor
- Insulin like Growth Factor 1
- Human Albumin
- Alpha-2- Macroglobulin
- Fibrinogen
Functions of Key Plasma Components
- Hepatocyte Growth Factor: A multifunctional protein that stimulates the proliferation and migration of progenitor cells and plays an intricate role in tissue regeneration and skeletal muscle repair. Works synergistically with VEGF for neovascularization and angiogenesis.
- Insulin Like Growth Factor-1: Responsible for cell growth, differentiation, and matrix synthesis. IGF-1 is retained in PPP and is critical for stem cell migration and regenerative stimulation.
- Human Albumin: Constitutes 60% of plasma protein and supports osmotic balance, molecule transport, anti-microbial defense, and stem cell recruitment.
- Alpha-2-Macroglobulin: Inhibits cartilage-degrading enzymes, traps inflammatory cytokines, and supports joint health.
- Fibrinogen: Facilitates clotting, traps invaders, and supports leukocyte recruitment and wound healing.
Exosomes in Platelet Poor Plasma
These are small extracellular vesicles that mediate intracellular communication and contain bioactive molecules influencing cellular processes. Actions of exosomes include:
- Enhancement of endothelial cell viability and migration promoting angiogenesis
- Stimulation of fibroblastic proliferation and extracellular matrix remodeling
- Modulation of immune responses by influencing macrophage polarization from M1 (inflammatory) to M2 (anti-inflammatory)
- Promotion of keratinocyte migration and re-epithelialization
Therapeutic Applications of Platelet Poor Plasma
PPP has been investigated and proven to have efficacy in various therapeutic areas of regeneration including:
- Angiogenesis: Growth factors and exosomes stimulate blood vessel formation and oxygenation
- Inflammation Modulation: Cytokines support transition to anti-inflammatory phenotypes
- Keratinocyte Migration: Growth factors support epithelialization
- Inhibition of Fibrosis: Modulates fibroblasts to prevent excessive matrix buildup
- Tissue Repair: Supplies regenerative molecules that support structural healing
Author’s Perspective on Platelet Poor Plasma
Authors note: I previously wrote an article entitled, Don’t Throw the Baby Out with the Bath Water. This article championed the use of platelet poor plasma along with platelet rich plasma for a variety of regenerative treatments. With newer studies recently published, the importance of a partial use of PPP along with PRP is magnified and the molecular physiology is explained in detail. Certain growth factors, as well as other important proteins are not concentrated or even contained on the platelets and reside in the plasma. These molecules have significant cellular reparative function and should not be eliminated in regenerative therapy. Therefore, PRP and some PPP would provide an augmented cocktail when performing regenerative treatments.
Studies Supporting PPP in Regenerative Medicine
- Advances in Regenerative Medicine Based Approaches for Skin Regeneration and Rejuvenation, Front Bioeng Biotechnol 2025 Feb 12:13:1527854 PMID 40013305
- Advancements in Regenerative Therapies for Orthopedics: A Comprehensive Review of Platelet Rich Plasma, Mesenchymal Stem Cells, Peptide Therapies, and Biomimetic Applications, J Clin Med 2025 Mar 18;14(6):2061 PMID 40142869
- Profound Properties of Protein Rich, Platelet Rich Plasma Matrices as Novel, Multi-Purpose Biological Platforms in Tissue Repair, Regeneration, and Wound Healing, Int J Mol Sci 2024 Jul 19(14):7914 PMID 39063156
Juventix: Advancing Platelet-Based Therapies
Juventix Regenerative Medical is an industry leader in the regenerative medical field. Our Platelet Rich Plasma Kits are FDA cleared and designed for safety, sterility and effectiveness. Our kits are scientifically manufactured to provide a platelet concentrate, devoid of red blood cells with a minimum number of leukocytes that are critical for the regenerative process.
Innovative Tools from Juventix
Juventix Regenerative Medical offers a patented LED Activator to activate the platelets and begin the regenerative process. The activation is a critical step in the release of growth factors, cytokines and bioactive proteins from the granules that are contained on the platelets and is accomplished with LED light. This negates the use of chemical additives such as Calcium Chloride, Thrombin or Collagen. This mode of activation by LED light provides sustained growth factor release versus older methods of activation while adhering to the minimal manipulation standards of the FDA.
This activation should always be accomplished after the gentle swirl of the centrifuged product to maximize the number of captured platelets.
With our premier line of products, services and devices and support from our experienced staff, Juventix Regenerative Medical is poised to aid any professional, whether medical, regenerative or aesthetic to provide enhanced clinical outcomes while increasing patient satisfaction.
RESTORE, REVIVE, REGENERATE — JUVENTIX REGENERATIVE MEDICAL
Regenerative Regards,
Dr. Robert McGrath
