Regenerative Skin Wound Healing in Mammals: State-of-the-Art on Growth Factor and Stem Cell Based Treatments

Abstract

Mammal skin has a crucial function in several life-preserving processes such as hydration, protection against chemicals and pathogens, initialization of vitamin D synthesis, excretion and heat regulation. Severe damage of the skin may therefore be life-threatening. Skin wound repair is a multiphased, yet well-orchestrated process including the interaction of various cell types, growth factors and cytokines aiming at closure of the skin and preferably resulting in tissue repair. Regardless various therapeutic modalities targeting at enhancing wound healing, the development of novel approaches for this pathology remains a clinical challenge. The time-consuming conservative wound management is mainly restricted to wound repair rather than restitution of the tissue integrity (the so-called “restitutio ad integrum”). Therefore, there is a continued search towards more efficacious wound therapies to reduce health care burden, provide patients with long-term relief and ultimately scarless wound healing. Recent in vivo and in vitro studies on the use of skin wound regenerative therapies provide encouraging results, but more protracted studies will have to determine whether the effect of observed effects are clinically significant and whether regeneration rather than repair can be achieved. For all the aforementioned reasons, this article reviews the emerging field of regenerative skin wound healing in mammals with particular emphasis on growth factor- and stem cell-based therapies.

In vitro and in vivo effects of PDGF-BB delivery strategies on tendon healing: a review

“…The PDGF-BB dimer -the mostly investigated isoform -is the only one that can bind to all three different surface PDGF receptors (PDGFRs) and trigger different signalling cascades, thus being called the universal isoform of PDGF. Compared to other growth factors, PDGF-BB has a well-established safety profile, approved by the Food and Drug Administration (FDA) (Borena et al, 2015), and formulations supporting wound healing in foot ulcers, as well as, bone regeneration are on the market [Regranex Gel ® (Smith&Nephew, London, UK) and GEM 21S ® (Luitpold, Pharmaceuticals, Shirley, NY, USA)] (Howard et al, 2014;Ma et al, 2015). In chronic foot ulcers, topical application of rhPDGF led to a significant increase (by 43 %) in the incidence of complete wound closure and decrease in healing time (by 32 %) over placebo-controlled wound care, resulting in the FDA approval of Regranex Gel ® (Wieman et al, 1998).…”

Estrogen Accelerates Cutaneous Wound Healing by Promoting Proliferation of Epidermal Keratinocytes via Erk/Akt Signaling Pathway

“…Normal cutaneous wound healing is a complicated process involving three overlapping phases, namely the inflammatory, proliferative, and remodeling phases [1][2][3]. Each phase requires coordinated effects of various cell types, including keratinocytes [4,5], fibroblasts [6], immune cells [7], etc., the disturbance of which in any phase leads to delayed cutaneous wound healing [8].…”

Growth Differentiation Factor-9 Promotes Fibroblast Proliferation and Migration in Keloids through the Smad2/3 Pathway

“…The development of steroid tapes and plasters has significantly improved the effect of steroid injections when used in combination [7,8]. Besides, stem cell based treatment such as mesenchymal stem cells, hematopoietic stem cells, and skin-derived precursors in wound healing is progressively being valued, but more protracted studies are needed to determine whether the observed effects are clinically significant [9][10][11]. Despite the availability of many therapeutic options, an optimal treatment modality has not been identified to date, underscoring the need to improve our understanding of the mechanisms of keloid formation.…”