Open finger tip healing and replacement after distal amputation in Rhesus monkey with comparison to limb regeneration in lower vertebrates

Abstract

The left thumbs and great toes of three 8 1/2 month old Rhesus monkeys (Macaca mulatta) were amputated in guillotine fashion one millimeter distal to the base of the nail and allowed to heal by the conservative open wound method. Healing occurred in seven to ten days in these small digits. Each of the thumbs and toes grew back with some blunting and shortening of the digit tips, but were functional. The new structures were cosmetically pleasing as in the human instances. The nails grew essentially to normal size and shape supported by the remaining portions of the distal phalanges. Histological studies showed no evidence of blastema formation such as is observed in the regenerating limb of the Urodele (newt) taken as the comparative representative. The possibility of improving the regrowth is discussed against the background of our knowledge of the importance of nerve during limb regeneration in lower vertebrates.

Wound healing and blastema formation in regenerating digit tips of adult mice

“…Digit tip regeneration in various mammalian species, including mice (Muneoka et al, 2008), rats (Said et al, 2004), monkeys (Singer et al, 1987) and humans (Illingworth, 1972) have been described in previous studies. The mouse digit has become a useful model to study mammalian regeneration because of a number of factors, including the description of strain-specific variation in response (Chadwick et al, 2007) and the identification of a regeneration defective mutant line (Han et al, 2003).…”

“…Digit tip regeneration has also been documented in rats and monkeys (Said et al, 2004; Singer et al, 1987), and there is an extensive clinical literature demonstrating regeneration of human fingertips following amputation injury (Illingworth, 1974; see Muller et al, 1999). In mice, digit tip regeneration has been demonstrated in embryonic, neonatal and adult models (Borgens, 1982; Reginelli et al, 1995; Neufeld and Zhao, 1995).…”

Macrophages are necessary for epimorphic regeneration in African spiny mice

“…Yet, the fact that some mammals exhibit epimorphic regeneration (e.g. rodent and primate digit tips, rabbit and spiny mice ear punches and skin) (Borgens, 1982; Gawriluk et al, 2016; Goss and Grimes, 1975; Han et al, 2008; Joseph and Dyson, 1966; Neufeld and Zhao, 1993; Seifert et al, 2012a; Singer et al, 1987) suggests that regeneration can occur despite a complex adaptive immune system. Different immune system components and inherent physiological differences between mammals and traditional regeneration models like salamanders, newts and zebrafish (e.g.…”

Unraveling the Molecular Basis for Regenerative Cellular Plasticity

“…Numerous studies over the past three decades have shown that mammals, including humans, can regenerate their digit tips provided the amputation plane is distal to the terminal phalangeal joint (Douglas 1972; Illingworth 1974; Borgens 1982; Singer et al 1987). However, Msx1 -deficient mice exhibit impaired fetal digit-tip regeneration, a phenotype that can be rescued in ex vivo cultures in a dose-dependent manner by application of exogenous BMP4 (Han et al 2003).…”