Fibroblastos en la cicatrización de heridas y la regeneración de la piel
Wound healing and regenerative medicine are closely related. Although any dermal wound in an adult, even if treated, will result in a scar, science continues to seek the total repair of wounds through the regeneration of functional native tissue.
Until recently, there were few truly effective therapies that accelerate healing and reduce its pathological states, such as hypertrophic scars and keloids, but there have been many therapeutic innovations in scar modulation in recent years. The most relevant include therapies involving the delivery of viable fibroblasts to the wound site and the manipulation of fibroblast behavior.
Today, we will look at recent advances in the understanding of fibroblasts in relation to cutaneous wound healing and relevant developments in clinical wound therapies.
The importance of fibroblasts in the healing process
Human wound healing can be considered as a spectrum, with typical scar formation representing the "normal" phenotype; chronic wounds at one end and hyperproliferative scars and even keloids at the other. Previous studies have begun to investigate the mechanisms by which fibroblast dysfunction could contribute to pathological states of wound healing.
During the early stages of healing, platelets are recruited to the open wound and deposit fibrin, which serves as a preliminary extracellular matrix, to stop bleeding. During the subsequent stages, immune cells, including neutrophils followed by macrophages, are recruited to the wound and remove dead and residual tissue in preparation for healing. New blood vessels sprout around the site, fibroblasts appear in anticipation of scar formation, and keratinocytes begin to migrate to cover the surface of the cutaneous wound.
Finally, during the remodeling phases of healing, the keratinocytes have covered the site and, underneath, the fibroblasts deposit a new extracellular matrix replacing the fibrin plug, which is then remodeled to form the “final scar.” At the same time, new blood vessels are pruned and nerves begin to regenerate.
Laboratory studies continue to show the striking heterogeneity of cutaneous fibroblasts. The concept that dermal fibroblasts represent multiple distinct subpopulations is an important advance in our understanding of skin pathophysiology and serves as a new perspective from which the innovation of new wound therapies may be possible.
Dermal fibroblasts come from two different lineages. The upper dermal lineage is involved with hair follicles, while the lower one synthesizes ECM and is related to adipocytes. Notably, it was discovered that the lower lineage is largely responsible for dermal repair after a wound, explaining why scar tissue in humans is particularly rich in ECM and lacks hair follicles. In other words, fibroblasts from hypertrophic scars resemble fibroblasts from deeper dermal layers more closely.
These cells can be identified through clinical markers and their ablation reduces the formation of raised scars, although this can also delay wound healing. Furthermore, although the epidermal and hair follicle fibroblast lineages are distinct, under stress conditions this distinction is attenuated. These findings go some way toward explaining why the response to tissue injury can be highly variable between different individuals and pathological states.
Growth factor, culture, and fibroblast reinsertion therapies
It is known that several growth factors stimulate the division, activity, and/or differentiation of fibroblasts. Effective wound treatments demand an agent that reflects the complex in vivo environment of cell types and growth factors. One approach has been to deliver viable allogeneic cells, including fibroblasts, to the wound site. These cells do not persist indefinitely, but serve as a source of growth factors and cytokines to support the function of the patient's own cells.
While all these products have already been used clinically for a wide variety of wound types, further characterization of the different populations of skin cells is allowing the development of increasingly effective autologous cell-based treatments.
At FCells we are pioneers in autologous fibroblast treatment in Mexico, and we have the only process authorized by COFEPRIS and the FDA. You can offer your patients an efficient and science-backed option to regenerate skin youth, diminish scars, and accelerate post-surgical healing processes. Call us and become one of our experts!
Related content: Fibroblasts for hand wrinkles
REFERENCES:
Skin wound healing process, endogenous fields and their relationship with chronic wounds: http://www.scielo.org.co/pdf/rfmun/v61n4/v61n4a14.pdf
Cell types, Fibroblast: https://mmegias.webs.uvigo.es/8-tipos-celulares/fibroblasto.php
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The Efficacy of Stem Cells in wound healing in 2024: A systematic review
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