Dermal Fibroblasts: Harnessing their Potential in Therapy

For years, the scientific community has overlooked dermal fibroblasts. However, the past decades have divulged their indispensable role in wound healing. Their involvement in tissue repair, immunomodulation, and disorders such as fibrosis and chronic wounds has been explored. In regenerative medicine, they have exhibited differentiation into osteocytes, adipocytes, neurons, hepatocytes, etc. as well as reprogramming into induced pluripotent stem cells.

Characteristics of Dermal Fibroblasts

Fibroblasts are cells present in the connective tissue. They synthesise the extracellular matrix (ECM), thus contributing to the structure and function of tissue. The identification markers of fibroblasts are platelet-derived growth factor (PDGFR) α, PDGFRβ, and CD90.

These spindle-shaped cells can be found in various tissues like the heart, liver, etc. The dermal fibroblasts are present beneath the epidermis in the dermis layer of skin. The integrity of the skin barrier depends highly on its ECM. The ECM components, such as collagen, elastin, and hyaluronic acid, maintain the strength, elasticity, and hydration of skin. They also participate in immune responses, wound repair, and tissue homeostasis. Transcriptional profiling has identified two different subsets of dermal fibroblasts- papillary and reticular fibroblasts. Aside from the different expression of markers and proteins present in both the subsets, papillary fibroblasts have considerably lower adipogenic potential than reticular fibroblasts.

Diverse Functions

Previously, dermal fibroblasts were considered to be only ECM-producing cells. However, tremendous research has proven the diversity in their functions and the consequent applications in various disorders.

Immune response: Dermal fibroblasts express pattern recognition receptors like TLRs and RLRs to recognize pathogens including bacteria, fungi, and viruses. They also secrete cytokines such as IL6, TNFα, IL8, IFNβ, etc., to mount an immune response. Moreover, they recruit immune cells to the infection site by releasing chemokines. Additionally, they also produce antimicrobial peptides that disrupt the pathogen membrane. Microbial challenge also triggers the release of matrix metalloproteinase to accelerate the pathogen clearance.

Wound Healing: Healing an injury or wound aims to restore the skin barrier via different phases. It generally leaves scar tissue. A scar tissue has distinguishing features from normal tissue. The quality and organization of ECM is a key difference between scar tissue and normal tissue. Thus, a successful wound healing entails minimal scar tissue. Any dysfunction in the wound healing process leads to chronic conditions such as fibrotic scars, keloid scarring, hypertrophic scarring, and non-healing ulcers. The healing process follows platelet activation to stop bleeding and immune cell stimulation to prevent infection. Fibroblasts aid in the inflammation by producing cytokines and facilitating immune cell infiltration. In the subsequent proliferation phase, which restores the matrix, fibroblasts proliferate and produce MMPs that degrade the fibrin clot. They also promote angiogenesis and migration of ECM components. In the final phase of healing, dermal fibroblasts differentiate into myofibroblasts, conferring contraction and stiffness to ECM.

Therapeutic Applications

Skin diseases like psoriasis, atopic dermatitis, and vitiligo, as well as injury to skin in the form of burns and chronic wounds, have necessitated the use of dermal fibroblasts to induce tissue repair and regeneration. 

Cell Therapy: The skin graft is a conventional technique for treating skin issues. However, they exhibit compromised skin functioning. Dermal fibroblasts have availed an alternative treatment modality. Studies have demonstrated accelerated wound healing after intradermal infusion of fibroblasts. With the evident effectiveness of fibroblasts, researchers have also attempted the combination of fibroblasts with other skin cells. A study by Slade et al. showed that a formulation of foreskin fibroblasts and keratinocytes reduced the wound size in patients with venous ulcers.

Artificial Skin: Three-dimensional tissue constructs have always been a better representation of in vivo tissue microenvironment. These constructs are also termed artificial skin. Initially, these skin substitutes constituted only the ECM, mostly based on collagen. However, as the scientific research unraveled the role of dermal fibroblasts, they were also seeded onto the ECM. Skin substitutes such as Dermagraft, Matriderm, and Integra are even commercially available. They contain dermal fibroblasts and the ECM material in the form of porous scaffolds. It even provided the opportunity to genetically engineer the fibroblasts for enhanced production of ECM.

Regenerative Medicine: The first induced pluripotent stem cells (iPSCs) were generated from mouse fibroblasts. iPSCs have a vast scope in regenerative medicine for therapeutic and research purposes. Since then, many scientists have reprogrammed fibroblasts into iPSCs, including dermal fibroblasts. Dermal fibroblasts offer the advantage of easy harvesting of cells and in vitro expansion, both of which ensure the acquisition of large quantities of cells.

Conclusion

The dermal fibroblasts have diverse functions and orchestrate tissue repair and regeneration. Their in vitro availability has notably advanced the therapeutic medicine. Kosheeka offers dermal fibroblasts isolated from diverse species, including human, rat, swine, and mouse. They are thoroughly characterized and tested for their quality to ensure hassle-free research.