The Blastema: Cells, Niches and Regeneration in Mammals

K. Muneoka
Department of Cell and Molecular Biology, Tulane Univerisity, New Orleans, LA

Fingertips in humans and toetips in rodents have the ability to regenerate after amputation injury. We have developed the regenerating toetip in mice as a model for eipmorphic regeneration in a mammal. During toetip regeneration a blastema of proliferating cells accumulate at the amputation site. These cells re-express genes that are known to play a critical role both in digit tip development and in digit tip regeneration in the embryo. The blastema eventually grows out and differentiates to form the distal region of the terminal phalangeal bone and surrounding connective tissue. The blastema is formed from cells derived from two sources: the bone marrow of the amputated stump bone, and the loose connective tissue associated with the stump bone. Prominent in the blastema is a reticular network composed of fibroblasts that establishes a transient biological scaffold that pre-patterns the regenerating terminal phalanx.

The data suggests that this reticular network forms a regeneration niche within which cell-type specific differentiation is controlled during the regeneration response. We propose that the formation of this reticular network plays a key role in coordinating skeletal regeneration. We are using this model system to understand molecular triggers critical for stimulating a regeneration response.

Keywords: Epimorphic regeneration, Mouse, Bone, Fibroblasts