Platelet-Derived Growth Factor (PDGF) is a dimeric glycoprotein composed of two protein chains, forming five different types from four subunits (PDGF-A, -B, -C, and -D). While famously stored in and released by platelets following injury, PDGF is also produced by other cells, including macrophages, smooth muscle cells, and endothelial cells. This protein binds to specific receptors on target cells, stimulating cell growth (mitogenesis), division, and directed movement (chemotaxis).
The Function of PDGF in Normal Tissue Repair
The controlled release of PDGF is an initial event in the body’s natural response to tissue damage. Upon injury, activated platelets release pre-stored PDGF into the wound site, initiating the hemostasis phase and the complex cascade of tissue repair.
PDGF’s first major action is chemotaxis, attracting specific cell types to the injury site. It recruits mesenchymal cells, such as fibroblasts and smooth muscle cells, and immune cells like monocytes and macrophages, which clear debris and prepare the wound bed. The influx of these cells is necessary for the subsequent proliferative phase of healing.
Once recruited, PDGF acts as a potent mitogen, driving the proliferation and activation of fibroblasts, the cells responsible for generating new connective tissue. This stimulation leads to the accelerated creation of a provisional extracellular matrix, which is the temporary scaffold necessary for tissue reconstruction. Furthermore, PDGF promotes angiogenesis, the formation of new blood vessels required to supply the growing repair tissue with oxygen and nutrients. The controlled, transient expression of PDGF during this acute phase ensures efficient tissue restoration.
PDGF’s Role in Disease and Uncontrolled Growth
When PDGF signaling becomes dysregulated, it can drive chronic disease states characterized by uncontrolled cell growth. If the production of PDGF ligands or the expression of their receptors (PDGFRs) becomes excessive or persistent, repair mechanisms shift into pathological processes. This imbalance is evident in oncology and fibrosis.
In oncology, over-expression of PDGF or PDGFRs contributes to the development and progression of various cancers. PDGF ligands secreted by tumor cells or the surrounding microenvironment promote cancer cell proliferation and survival. The signaling also affects the tumor microenvironment by recruiting fibroblasts, which transform into cancer-associated fibroblasts (CAFs).
Driven by constant PDGF stimulation, these CAFs deposit a dense, stiff extracellular matrix that supports tumor growth and invasion. Sustained PDGF signaling also promotes pathological angiogenesis, forming new blood vessels that feed the tumor. This activation has made PDGFRs a target for specific cancer therapies designed to block proliferative signaling.
Excessive and sustained PDGF signaling is a contributor to fibrotic disorders throughout the body, such as pulmonary fibrosis and atherosclerosis. Fibrosis is characterized by the chronic overproduction and accumulation of extracellular matrix components, leading to scarring and organ dysfunction. In conditions like scleroderma, elevated levels of PDGF and its receptors persistently activate fibroblasts in affected tissues. This chronic stimulation causes fibroblasts to differentiate into highly active myofibroblasts, which continuously secrete collagen and other matrix proteins, ultimately leading to tissue hardening and loss of function.
Clinical Applications of PDGF in Regenerative Medicine
The regenerative capabilities of PDGF have been harnessed in medicine through the use of exogenous, or externally applied, recombinant protein. Recombinant human PDGF-BB (rhPDGF-BB) is the most studied form and is manufactured to mimic the natural protein, providing a therapeutic boost to stalled healing processes.
This approach is most widely utilized in the treatment of chronic, non-healing wounds, such as diabetic foot ulcers, which often fail to complete the normal healing cascade. A topical gel containing rhPDGF-BB can be applied directly to the wound bed to re-initiate the proliferative phase. The applied growth factor attracts fibroblasts and macrophages, stimulating the formation of granulation tissue and accelerating wound closure.
Beyond chronic dermal wounds, rhPDGF is used in periodontal and orthopedic applications to promote bone and soft tissue regeneration. In dental procedures, it is commonly combined with bone graft materials to enhance the healing of bone defects, such as those found around tooth roots or in preparation for implants. The ability of rhPDGF to recruit osteoprogenitor cells and promote angiogenesis makes it valuable for stimulating the complex process of bone remodeling and incorporation of the graft material.