Physiological aspects of blastema formation in mice
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abstract
2018 by Taylor & Francis Group, LLC. The regeneration of the mouse digit tip and the human fingertip represent mammalian examples of endogenous regenerative responses and provide models for uncovering mechanisms controlling functional regeneration. Mouse digit-tip regeneration involves a series of phases similar to other regeneration models: (1) wound healing, (2) blastema formation, and (3) redifferentiation. The regeneration process is viewed as two distinct transformations: (1) mature tissue to blastema and (2) blastema to redifferentiation. Wound healing involves an osteoclast-driven degradation of stump bone that remodels the existing bone and establishes an interface for the newly regenerated bone. The recruitment of progenitor cells that form the blastema involves the SDF1/CXCR4 signaling pathway and the blastema itself is characterized as an avascular and hypoxic microenvironment. The regulation of oxygen availability plays a key role in the first transformation to form the blastema. The redifferentiation of regenerated bone occurs by the direct ossification of woven bone that is distinct from the cortical bone that is amputated; thus, this response is not anatomically perfect but is physiologically functional. The regenerating digit tip represents an example of a successful regenerative engineering project that has evolved, and can serve as a model for the development of therapeutic strategies for regenerative medicine.
