Shh is the most widely expressed and potent and it affects the cells in an autocrine/paracrine manner (Delloye-Bourgeois et al., 2013). Shh knockout leads to embryonic death in mice (Chiang et al., 1996) while dhh knockout animals had minor defects (Bitgood et al., 1996).

Although the three hedgehog proteins in vertebrates – sonic hedgehog (shh), Indian hedgehog and desert hedgehog (dhh) – are highly homologous and share receptors and intracellular signal pathways (Carpenter et al., 1998 Johnson and Scott, 1998), their potency and function differ. Recent studies refer to the hedgehog proteins in regulation of primitive haematopoietic cells (Bhardwaj et al., 2001), mammary stem cells (Liu et al., 2006) and neural stem cell (Ahn and Joyner, 2005) involved in adult tissue maintenance and regeneration. Therefore, the complex interaction of stem cells and soluble factors in wound sites has been examined through an in vitro study. Despite limitations in embryonic stem cells (ESCs) for skin wound healing, a previous study reported that mouse ESCs (mESCs) reconstitute into fully differentiated skin (Coraux et al., 2003) and the topical application of ESCs enhance skin wound healing in diabetic rats (Lee et al., 2011) as well as the mesenchymal stem cells (MSCs) recovered through the paracrine manner of biological active molecules (Chen et al., 2008). Additionally, stem cells secrete various growth factors, cytokines, chemokines and bioactive lipids into the micro-environment in an autocrine/paracrine manner (Guo and Dipietro, 2010 Ratajczak et al., 2012).

Although the mechanism underlying stem cell-induced skin wound healing is not fully understood, stem cells play key roles in wound neo-vascularization, wound contraction, keratinization and recovery (Liu et al., 2008). Besides self-renewal, stem cells promote wound healing and reduce inflammation (Wu et al., 2007). Skin wound healing is a well-organized process of cell migration and proliferation that involves extracellular matrix deposition, angiogenesis, and tissue remodelling.

Sonic windows zone skins