Following a skin injury, the damaged tissue is repaired through the coordinated biological actions that constitute the cutaneous healing response. In mammals, repaired skin is not identical to intact uninjured skin, however, and this disparity may be caused by differences in the mechanisms that regulate postnatal cutaneous wound repair compared to embryonic skin development. Improving our understanding of the molecular pathways that are involved in these processes is essential to generate new therapies for wound healing complications. Here we focus on the roles of several key developmental signaling pathways (Wnt/β-catenin, TGF-β, Hedgehog, Notch) in mammalian cutaneous wound repair, and compare this to their function in skin development. We discuss the varying responses to cutaneous injury across the taxa, ranging from complete regeneration to scar tissue formation. Finally, we outline how research into the role of developmental pathways during skin repair has contributed to current wound therapies, and holds potential for the development of more effective treatments.

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Cutaneous wound healing: recruiting developmental pathways for regeneration

Potential cellular and molecular causes of hypertrophic scar formation

Promotion of skin regeneration in diabetic rats by electrospun core-sheath fibers loaded with basic fibroblast growth factor.

The skin offers a perfect model system for studying the wound healing cascade, which involves a finely tuned interplay between several cell types, pathways and processes. The dysregulation of these factors may lead to wound healing disorders resulting in chronic wounds, as well as abnormal scars such as hypertrophic and keloid scars. As the contribution of stem cells towards tissue regeneration and wound healing is increasingly appreciated, a rising number of stem cell therapies for cutaneous wounds are currently under development, encouraged by emerging preliminary findings in both animal models and human studies. However, we still lack an in-depth understanding of the underlying mechanisms through which stem cells contribute to cutaneous wound healing. The aim of this review is, therefore, to present a critical synthesis of our current understanding of the role of stem cells in normal cutaneous wound healing. In addition to summarizing wound healing principles and related key molecular and cellular players, we discuss the potential participation of different cutaneous stem cell populations in wound healing, and list corresponding stem cells markers. In summary, this review delineates current strategies, future applications, and limitations of stem cell-based or stem cell-targeted therapy in the management of acute and chronic skin wounds.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1600-0625.2009.00942.x

Exploring the role of stem cells in cutaneous wound healing.

Inflammation is a complex, multi-scale biologic response to stress that is also required for repair and regeneration after injury. Despite the repository of detailed data about the cellular and molecular processes involved in inflammation, including some understanding of its pathophysiology, little progress has been made in treating the severe inflammatory syndrome of sepsis. To address the gap between basic science knowledge and therapy for sepsis, a community of biologists and physicians is using systems biology approaches in hopes of yielding basic insights into the biology of inflammation. “Systems biology” is a discipline that combines experimental discovery with mathematical modeling to aid in the understanding of the dynamic global organization and function of a biologic system (cell to organ to organism). We propose the term translational systems biology for the application of similar tools and engineering principles to biologic systems with the primary goal of optimizing clinical practice. We describe the efforts to use translational systems biology to develop an integrated framework to gain insight into the problem of acute inflammation. Progress in understanding inflammation using translational systems biology tools highlights the promise of this multidisciplinary field. Future advances in understanding complex medical problems are highly dependent on methodological advances and integration of the computational systems biology community with biologists and clinicians.

/pdf/translational-systems-biology-of-inflammation-hu4vc6zrzg.pdf

Translational Systems Biology of Inflammation

In order to identify a means to reduce scar formation of the skin after incision, this study examined the effect of local administration of basic fibroblast growth factor (bFGF) in humans. bFGF was administered to a sutured wound immediately after an operation. The drug was injected once into the dermis of the margins of wounds using a 27G needle or rinsing after performing dermostitches. The lengths of the treated wounds varied from 1 to 32 cm, and the subjects were 2-86 years old. Sutured wounds after excision of skin tumors from the face, trunk, and limbs and sutured wounds such as those at the donor sites of full-thickness skin grafts were treated with low-dose bFGF injections (0.1 microg/cm wound; Group 2), high-dose bFGF injections (1 microg/cm wound; Group 3), and rinsed with high-dose bFGF (1 microg/cm wound; Group 4). No patient treated with bFGF had hypertrophic scars, while some patients had hypertrophic or very wide scars in the control group (Group 1), and the ratios of minimum scarring of Group 2 (p<0.001), Group 3 (p<0.0001), and Group 4 (p<0.0001) were statistically significantly higher than those of Group 1. Postoperative administration of bFGF inhibited hypertrophic scarring and widening of remaining scars without any serious side effects.

Basic fibroblast growth factor reduces scar formation in acute incisional wounds

Polymerase chain reaction(PCR)を用いると帯状疱疹患者の末梢血リンパ球からも水痘帯状疱疹ウイルス(varicella-zoster virus: VZV)核酸が検出される。本研究では，札幌医大附属病院皮膚科に入院しビダラビン(アラセナ®A)600mg/日を5日間投与された帯状疱疹患者10例よりリンパ球を調製し，PCRによって末梢血リンパ球のVZV gene 29およびgene 62のDNAおよびRNAの検出を行った。検討した10例のうち基礎疾患のある重症帯状疱疹の3例と中等症の1例は補体結合反応値が128倍と高値を示し，さらにPCRによりVZV DNAおよびRNAが検出された。しかし，これら4症例とも入院7～10日後(第14病日)には末梢血リンパ球からウイルス核酸は検出されなかった。他の中等症の1例と軽症5例の末梢血リンパ球からはVZV gene 29あるいは62のDNAとRNAは検出されなかった。患部皮疹が潰瘍化した重症の1例を除き，いずれの症例も3週間以内に上皮化し2～4週間後の帯状疱疹関連神経痛はVASスコアで0/5あるいは1/5まで低下した。これらの結果より，重症例ではウイルス抗体価が上昇し末梢血リンパ球にVZV遺伝子が検出され少なくとも一部のウイルス遺伝子が発現しているが，ビダラビン600mg/日，5日間の投与によって発症2週間後には末梢血よりウイルスが駆逐されると考えられた。

Risa Kikuchi

Papers

Basic fibroblast growth factor reduces scar formation in acute incisional wounds

Detection of Varicella-Zoster Virus Nucleic Acids in Peripheral Lymphocytes from Patients with Herpes Zoster