The mammalian blastema: regeneration at our fingertips

Abstract

In the mouse, digit tip regeneration progresses through a series of discrete stages that include inflammation, histolysis, epidermal closure, blastema formation, and redifferentiation. Recent studies reveal how each regenerative stage influences subsequent stages to establish a blastema that directs the successful regeneration of a complex mammalian structure. The focus of this review is on early events of healing and how an amputation wound transitions into a functional blastema. The stepwise formation of a mammalian blastema is proposed to provide a model for how specific targeted treatments can enhance regenerative performance in humans.

Mechanisms of urodele limb regeneration

“…Research on urodele limb regeneration will continue to inform this challenge, especially through comparative studies between urodele and regeneration‐deficient anuran limbs (Rao et al., 2014) and between position‐specific differences in the regenerative ability of mammalian appendages (Simkin, Sammarco, & Dawson, 2015). Why amputated urodele appendages regenerate and amputated anuran and mammalian appendages regenerate hypomorphically or not at all has been a long‐standing evolutionary question.…”

“…Some gene activities, progenitor cells, and tissue interactions in regenerating salamander limbs are similar to those of regenerating mouse digit tips (for reviews see Simkin et al., 2015; Zielens, Ransom, Leavitt, & Longaker, 2016). These similarities have encouraged the idea that mammals have retained a latent ancestral genetic circuitry for appendage regeneration that might be activated by appropriate interventions and applied to the goal of regenerating a human limb.…”

The Impact of Aging on Mechanisms of Mammalian Epimorphic Regeneration

“…However, instead of scarring, a signaling center consisting of the nail and wound epithelium induces the formation of a blastema, an aggregate of undifferentiated proliferating cells that mediate the regeneration response. Once recruited by dedifferentiation or stem cell activation, progenitor cells migrate and proliferate to form a blastema, which differentiates to create the newly regenerated structure [9]. In the next sections, we will describe the major cellular and molecular mechanisms of mammalian epimorphic regeneration, exemplified by digit tip regeneration, and present some ideas how aging likely interferes with regeneration.…”

Decellularized Bovine Articular Cartilage Matrix Reinforced by Carboxylated-SWCNT for Tissue Engineering Application

“…The progenitor cells derived from the blastema cells tend to have osteogenic, adipogenic and chondrogenic differentiation potential (Baghaban Eslaminejad and Bordbar 2013). The blastema ring model of the rabbit ear is a simple and effective model which can be used for tissue engineering studies (Hashemzadeh et al 2015; Simkin et al 2015). With respect to the above findings, the hypothesis of using Carboxylated-SWCNT in improving the capacity of three-dimensional scaffolding of decellularized cartilage for tissue engineering application was introduced and then these reinforced scaffold were assembled with blastema ring to investigate interaction between these scaffolds and the living cells so that they can be used in the studies of cartilage tissues engineering.…”