Regeneration

Morphological regeneration is a reactivation of development in postembryonic life to restore missing tissue. Its most spectacular aspects are the demonstration of multipotent properties of specific tissue and that the correct positional information is re-specified, so that normal body structures such as complete extremities or retinas are formed. Only a few aquatic vertebrates such as salamanders and newts possess the potency for regeneration. Among invertebrates, species of much lower order, such as insects (crickets, cockroaches), flatworms (planaria), and coelenterates (Hydra), are able to regenerate lost or lesioned organs.

Despite this large number of species with regeneration potencies, microgravity investigations were limited to studies on the regeneration of lens, forelimb, and tail in Pleurodeles waitI during the Bion-10 and -11 flights (Grinfeld et al. 1994; Grigoryan et al. 2002), and of abdominal appendages or cerci in crickets (Horn et al. 2001) (see Figure 5-01). The main observation was that lost or lesioned parts of the body could regenerate in microgravity. In some instances, cell proliferation in the flight animals was increased. Differences became less pronounced the longer the time span was between lesion and onset of microgravity. Microgravity experience persists in intact animals for some time because newts flown intact and operated after the flight regenerated faster than 1-g ground controls (Grigoryan et al. 2002).

Retina regeneration can be induced by several lesion techniques, such as by removal of neural retina using microsurgery or by optic nerve transsection. An experiment performed on the two-week Bion-11 flight revealed an intensification of regenerative processes. In particular, the

17 Diapause is a period in the life cycle of an insect during which development is temporarily suspended. Diapause is usually induced by environmental signals or extreme conditions like winter or summer.

proliferative activity as shown by the number of [3H]-thymidine-labeled cells in the retinal pigmented epithelium, eye growth zone, and other retinal areas was 1.2 to 1.5 times higher in flown salamanders compared to ground controls (Grigoryan et al. 2002) (Figure 5-24).

Many features of tail regeneration in the salamander, including blastema elongation, neuronal tube, cartilage of future vertebrate, muscles and connective tissue, proceeds in microgravity at the same pace as in normal gravity. The only condition is that, at launch, the tail blastemas must have just formed a 1-mm thick translucent, convex layer. Similarly, some molecular markers of central nervous system activity such as Glial Fibrillary Acidic Protein (GFAP), specific intermediate filaments NF150, and Tyrosine Hydrolase (TOH), were found in both space and ground groups in similar amounts. However, other features of tail regeneration were modified, including the connective tissue of the blastema of salamanders exposed to 0-g that developed more GABA-positive cells than ground controls (Grinfeld et al. 1994).

Figure 5-24. Regeneration of the retina under spaceflight conditions in the newt Pleurodetes wait!. Left: Selected stages of neuronal regeneration after lesioning of the optic nerve. Stage 0: Operation; Stage 1: Degeneration of original neural retina (ONR); Stages 4: Formation of early retinaI regenerate (ERR) by trans-differentiating cells of the retinaI pigmented epithelium (RPE) and cells of eye growth zone; Stage 7: Morphogenesis of newly formed retina and regeneration of optic nerve. Right: Percentage of f3TJ-thymidine-labeled nuclei in the central part of the neural retina when lesion was performed two (L-2 weeks) and four weeks (L-4 weeks) before launch in space-flown newts (F) compared to the basal (B) and synchronous (S) control groups. The "basal" measurements describe the status of regeneration at the day of launch. The synchronous group is the ground control group kept under the same conditions and timeline as the flight animals and fixed for histological studies on the same day after landing as the flight animals. Adapted from Grigoiyan et al. (2002).

Figure 5-24. Regeneration of the retina under spaceflight conditions in the newt Pleurodetes wait!. Left: Selected stages of neuronal regeneration after lesioning of the optic nerve. Stage 0: Operation; Stage 1: Degeneration of original neural retina (ONR); Stages 4: Formation of early retinaI regenerate (ERR) by trans-differentiating cells of the retinaI pigmented epithelium (RPE) and cells of eye growth zone; Stage 7: Morphogenesis of newly formed retina and regeneration of optic nerve. Right: Percentage of f3TJ-thymidine-labeled nuclei in the central part of the neural retina when lesion was performed two (L-2 weeks) and four weeks (L-4 weeks) before launch in space-flown newts (F) compared to the basal (B) and synchronous (S) control groups. The "basal" measurements describe the status of regeneration at the day of launch. The synchronous group is the ground control group kept under the same conditions and timeline as the flight animals and fixed for histological studies on the same day after landing as the flight animals. Adapted from Grigoiyan et al. (2002).

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