Biomedical Engineering Reference
In-Depth Information
is the regeneration of crushed or lost distal tips of fingers in young children (Il-
lingworth 1974) and mice (Takeo et al. 2013). Other examples that have been par-
ticularly well documented include the capacity of rabbits to fill in holes that were
punched through their external ears and the annual regrowth of deer antlers from the
wound that forms when the old antlers are shed in the spring (Goss 1980; Stocum
1995). Similarities between regeneration of ear punch holes in rodents and ampu-
tated limbs in the axolotl have been pursued with emphasis on the cell cycles that
contribute to the development of the blastema (Heber-Katz et al. 2013). These ex-
amples of epimorphic regeneration, especially the amphibian models, are currently
being studied intensively by several biologists in an effort to identify the genetic
or acquired characteristics that are responsible for these spontaneous regenerative
phenomena (Takeo et al. 2013). Local evolution is often as important as a purely
ancestral mechanism in explaining limb regeneration: salamanders are the only
adult tetrapod vertebrates able to regenerate their limbs hypothetically due to the
existence of salamander-specific genes that play a significant role in the mechanism
of regeneration (Brockes and Gates 2014). In this volume we focus instead on the
adult mammal, specifically on phenomena of induced regeneration in tissues where
spontaneous regeneration is unknown.
The mammalian fetus is capable of regeneration provided it is at an early enough
point along gestation (Colwell et al. 2005). Surveys of organ healing in the mam-
malian fetus have emphasized the absence of scarring in several animal models of
injury during the early stages of gestation (Ferguson and O'Kane 2004). This topic
is discussed extensively in this volume.
1.5
A Choice of Paradigm for Studies of Regeneration
The paradigm of limb amputation in the urodeles, young frogs (tadpoles), and liz-
ards is an instance of spontaneous regeneration (Hay 1966; Goss 1969; Wallace
1981; Stocum 1995; Call and Tsonis 2005; Heber-Katz et al. 2013; Brockes and
Gates 2014). In these animal models the progress of regeneration of an entire limb
can be studied in detail. The injured site itself (site of limb amputation) is quite
complex, reflecting loss of an entire hierarchy of tissues and organs rather than loss
of a single organ. Due to the large scale of injury, study of limb amputation and its
aftermath have been restricted to small amphibians and, for obvious reasons, are
rarely conducted experimentally with larger animals. Furthermore, a study of spon-
taneous regeneration with mammals is also quite challenging, being restricted to the
early fetal stage of gestation, understandably not a convenient experimental venue.
The critical distinction between studying the process of regeneration in amphib-
ian vs. mammalian models derives from the intrinsic difference in their response to
injury. In studies of amphibian limb regeneration the focus is on
reversible
injury.
Information obtained about the detailed genetic or other pathways towards spon-
taneous regeneration in amphibians may eventually become applicable in future
studies to the adult mammal, arguably the human, where severe injuries typically
do not heal spontaneously (see further sections; Christensen et al. 2002; Menger
