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PubMed2005

Macroarray-based analysis of tail regeneration in Xenopus laevis larvae.

Xenopus larvae possess a remarkable ability to regenerate their tails after they have been severed. To gain an understanding of the molecular mechanisms underlying tail regeneration, we performed a cDNA macroarray-based analysis of gene expression. A Xenopus cDNA macroarray representing 42,240 independent clones was differentially hybridized with probes synthesized from the total RNA of normal and regenerating tails. Temporal expression analysis revealed that the up-regulated genes could be grouped into early or late responding genes. A comparative expression analysis revealed that most genes showed similar expression patterns between tail development and regeneration. However, some genes showed regeneration-specific expression. Finally, we identified 48 up-regulated genes that fell into several categories based on their putative functions. These categories reflect the various processes that take place during regeneration, such as inflammation response, wound healing, cell proliferation, cell differentiation, and control of cell structure. Thus, we have identified a panel of genes that appear to be involved in the process of regeneration.

Animals↗
PubMed1996

Auxiliary liver transplantation: regeneration of the native liver and outcome in 30 patients with fulminant hepatic failure--a multicenter European study.

Auxiliary liver transplantation (LT) is a special procedure of LT which could be proposed to patients with fulminant hepatic failure (FHF) and has for aim that complete regeneration of the native liver (NL) left in place will allow the graft recipient to resume normal liver function after allograft withdrawal. We report 30 cases of auxiliary LT performed for FHF in 12 European centers. Twenty-five of 30 patients were younger than 50 years. The cause of FHF was hepatitis A virus (HAV) in 4 patients, hepatitis B virus (HBV) in 7, paracetamol overdose in 5, ecstasy in 2, hepatotoxic drugs in 4, autoimmune hepatitis in 2, liver lesions of preeclampsia in 1 and unknown in 5. A postoperative, both clinical and histological follow-up of more than 3 weeks was obtained in 22 patients, enabling us to look for indicators predictive of NL regeneration and outcome. Histological changes observed in the NL included complete regeneration in 68%, incomplete regeneration with obvious fibrous sequelae in 14% and severe liver fibrosis or cirrhosis in 18%, of the 22 patients studied. The percentage and distribution of necrosis observed in tissue samples of the NL at the time of transplantation was not related to the final outcome. Complete NL regeneration was observed in 15 patients, out of whom 14 were younger than 40 years. Patients with complete regeneration were mainly affected by FHF due to HAV, HBV, or paracetamol overdose. After a follow-up of 18/11 (mean/median) months (range, 3 to 67 months), 19 of the 30 patients (63%) survived and 13 of them (68%), i.e., 43% of the 30 patients, had resumed normal NL function, with interrupted immunosuppression, the ultimate goal of emergency auxiliary LT. We conclude that, in patients with FHF, auxiliary LT is a procedure feasible in a number of centers and is associated with a complete regeneration capability of the NL in a majority of survivors, especially in those younger than 40 years. Confirmation of these encouraging preliminary results by large-scale prospective studies is required.

Adolescent↗
PubMed1975

Hemopoietic colony forming cells in regenerating mouse liver.

Cells from regenerating mouse liver removed 2-25 days post 68% hepatic resection have been assayed for in vivo colony forming capacity in soft agar (CFU-C), proliferative capacity in liquid culture, and in vivo spleen colony forming capacity (CFU-S). These studies demonstrated low concentrations of CFU-C and CFU-S in normal and sham operated liver, with an appreciable increase of both in regenerating liver, reaching maximum values in tissue removed 5--7 days post hepatic resection. Colony formation in agar by regenerating liver cells occurred in the absence of exogenous colony stimulating factor. Separation of liver cells on the basis of adherent properties prior to culture indicated concentration of CFU-C in the non-adherent fraction, while cells producing colony stimulating factor were concentrated in the adherent fraction. Foci of actively dividing cells of themacrophage and granulocyte series arose in liquid culture from preparations of sham operated and regenerating liver, although total cell formation was greater with regenerating liver. A small proportion of the colonies formed in agar from regenerating liver consisted of cords of epithelioid cells, which resembled hepatocytes and differed from the macrophages or granulocytes found in the majority of colonies, raising the possibility that regenerating hepatocytes form colonies in agar culture.

Animals↗
PubMed2003

Prospects for tooth regeneration in the 21st century: a perspective.

The prospects for tooth regeneration in the 21st century are compelling. Using the foundations of experimental embryology, developmental and molecular biology, the principles of biomimetics (the mimicking of biological processes), tooth regeneration is becoming a realistic possibility within the next few decades. The cellular, molecular, and developmental "rules" for tooth morphogenesis are rapidly being discovered. The knowledge gained from adult stem cell biology, especially associated with dentin, cartilage, and bone tissue regeneration, provides additional opportunities for eventual tooth organogenesis. The centuries of tooth development using xenotransplantation, allotransplantation, and autotransplantation have resulted in many important insights that can enhance tooth regeneration. In considering the future, several lines of evidence need to be considered: (1) enamel organ epithelia and dental papilla mesenchyme tissues contain stem cells during postnatal stages of life; (2) late cap stage and bell stage tooth organs contain stem cells; (3) odontogenic adult stem cells respond to mechanical as well as chemical "signals"; (4) presumably adult bone marrow as well as dental pulp tissues contain "odontogenic" stem cells; and (5) epithelial-mesenchymal interactions are pre-requisite for tooth regeneration. The authors express "guarded enthusiasm," yet there should be little doubt that adult stem cell-mediated tooth regeneration will be realized in the not too distant future. The prospects for tooth regeneration could be realized in the next few decades and could be rapidly utilized to improve the quality of human life in many nations around the world.

Dentistry, Operative↗
PubMed2002

Gallium nitrate: effects on cartilage during limb regeneration in the axolotl, Ambystoma mexicanum.

Gallium nitrate, a drug shown to have efficacy in Paget's disease of bone, hypercalcemia of malignancy, and a variety of experimental autoimmune diseases, also inhibits the growth of some types of cancer. We examined dose and timing of administration of gallium nitrate on limb regeneration in the Mexican axolotl, Ambystoma mexicanum. Administered by intraperitoneal injection, gallium nitrate inhibited limb regeneration in a dose-dependent manner. Gallium nitrate initially suppressed epithelial wound healing and subsequently distorted both anterior-posterior and proximo-distal chondrogenic patterns. Gallium nitrate given at three days after amputation severely inhibited regeneration at high doses (6.25 mg/axolotl) and altered the normal patterning of the regenerates at low doses (3.75 mg/axolotl). Administration of 6.25 mg of gallium nitrate at four or 14 days prior to amputation also inhibited regeneration. In amputated limbs of gallium-treated axolotls, the chondrocytes were lost from inside the radius/ulna. Limbs that regenerated after gallium treatment was terminated showed blastema formation preferentially over the ulna. New cartilage of the regenerate often attached to the sides of the existing radius/ulna proximally into the stump and less so to the distal cut ends. J. Exp. Zool. 293:384-394, 2002.

Ambystoma mexicanum↗
PubMed1975

Pattern formation in the imaginal wing disc of Drosophila melanogaster: fate map, regeneration and duplication.

Fragments of the wing disc of Drosophila (fig. 2) were either injected into mature third instar larvae for immediate metamorphosis, or cultured in adult abdomens for seven days before being transferred to larvae for metamorphosis. The structures differentiated during metamorphosis were then analysed. The results of the first series of experiments were used to construct an accurate fate map of the disc, and those of the second series were used to determine the regenerative properties of the disc. The fate map (fig. 7) shows presumptive proximal parts (notum, pleura, and dorsal and ventral hinge) at the two ends of the disc, with presumptive distal wing parts in between. During metamorphosis the disc epithelium folds upon itself along the presumptive wing border, bringing dorsal and ventral wing and hinge surfaces into apposition. The wing surfaces occupy a much smaller relative area, and the hinge parts a much larger relative area, in the fate map than in the adult structure. The cultured fragments, in general, behaved in accordance with the rule that when two cut surfaces are created by cutting across the disc, regeneration occurs from one of the cut surfaces and duplication occurs from the other (fig. 14). It was possible to define a level in the longitudinal axis of the disc from which regeneration proceeds outwards. Cut surfaces facing away from this level show regeneration, while cut surfaces facing this level undergo duplication. Similar behavior was found for the transverse axis, and for two diagonal series of cuts. Some fragments with two cut edges could regenerate from one edge while duplicating from the other, whereas others could regenerate from two cut edges simultaneously. However, fragments with four cut edges showed incomplete regeneration, and a high tendency to duplicate even though regeneration in all directions might have been expected on the basis of the other experiments.

Animals↗
PubMed1977

The relationship between growth, developmental stage and postamputation age of the regeneration blasterma of the newt, Notophthalmus viridescens.

The growth of the regeneration blastema of the newt forelimb has been quantitated and analyzed as a function of postamputation age, developmental stage, animal weight, animal length, and cross sectional diameter of the blastemal base in both the anteroposterior and dorsoventral dimensions. Correlation coefficients computed for these variables show that growth of the regenerate in both length and volume is more closely correlated with developmental stage than postamputation age. In addition, the results show a linear relation between the loge (regenerate length) and developmental stage, and between regenerate length and volume. Thus, length can be used to assess growth of the regenerate according to a developmental rather thana chronological time scale. There were no significant correlations between regenerate length or volume and animal length, animal weight or cross sectional dimensions of the blastemal base. These results show that one can use a randomly selected population of animals and study the growth of the regeneration blastema by relating to a developmental time scale through a logarithmic transformation of the linear growth data.

Amputation, Surgical↗
PubMed1984

Retinoic-acid-induced pattern completion in regenerating double anterior limbs of urodeles.

The effects of retinoic acid on the regeneration of double anterior lower arms in the adult newt, Notophthalmus viridescens, were investigated. Normally, double anterior lower arms regenerate a hypomorphic, symmetrical pattern of structures, which are distally complete; and double anterior upper arms regenerate a hypomorphic, symmetrical but distally incomplete pattern of structures. In limbs with a normal anteroposterior axis, the major effect of retinoic acid is to alter the proximodistal (PD) positional value of cells local at the amputation level to a much more proximal value, thereby creating duplications in the regenerate of structures proximal to the amputation plane (Thoms and Stocum, '84). Therefore, we predicted that double anterior lower arms treated with retinoic acid would regenerate like double anterior upper arms. However, in a substantial number of cases, each half of these double anterior lower arms regenerated a limb that was complete in the anteroposterior (AP) axis, with asymmetry corresponding to the half of origin. In addition, these regenerates were serially duplicated in the PD axis. These results indicate that retinoic acid can posteriorize the positional value of midline cells, leading to restoration of normal AP pattern, when the set of posterior-half positional values is removed from the cross section of the limb.

Amputation, Surgical↗
PubMed1985

Pattern-deficient forelimb regeneration in adult bullfrogs.

This study was designed to test the ability of adult bullfrogs (Rana catesbeiana) to regenerate forelimbs, both with and without various experimental treatments. Distal humerus-level forelimb amputations provided with additional deviated (sciatic) nerve and/or repeated soft-tissue injury exhibited considerable outgrowth. However, control sham-operated forelimbs also produced regenerates with comparable frequency, size, and morphological complexity. The lengths of the regenerates ranged from 0.4 to 2.6 cm, representing an outgrowth of 10-65% of the portion removed by the distal humerus amputation plane; some regenerates exhibited an external morphology indicative of digitlike structures. Some outgrowths were flexible but only one was capable of independent movement. Victoria Blue staining of whole regenerates revealed a variety of internal cartilage elements. Staining showed a single solid mass of cartilage in some regenerates while others had several individual and variably shaped cartilages projecting distally. Histological analysis also revealed the presence of connective tissue, striated muscle, and abundant nerve fibers in addition to the individual cartilage elements. We have tentatively termed these responses pattern-deficient regeneration.

Animals↗
PubMed1987

Influence of chromatographic fractions of extracts derived from bovine neural retina on newt (Notophthalmus viridescens) lens regeneration in vitro.

Removal of the ocular lens in adult newts (Notophthalmus viridescens) is followed by a series of cellular events leading to regeneration of a new lens by cell type conversion of pigmented iris epithelial cells at the dorsal pupillary margin (Yamada, Curr. Top. Dev. Biol. 2:247-283, 1967). Following depigmentation and five to seven cell divisions, iris epithelial cells redifferentiate into lens fiber cells and synthesize crystallin proteins (Yamada, Curr. Top. Dev. Biol. 2:247-283, 1967). This process is dependent upon neural retina in vivo (Stone, Anat. Rec. 131:151-172, 1958; Reyer, Dev. Biol. 14:214-225, 1966) and in vitro (Yamada et al., Differentiation 1:65-82, 1973). Acting on the hypothesis that the role of the neural retina is to promote passage of iris epithelial cells through the requisite number of cell cycles which will then allow them to redifferentiate as lens fiber cells (Yamada, in: Cell Biology of the Eye. Academic Press, New York, 1982), we undertook testing of the effects of eye-derived mitogenic substances, as well as other mitogens, on regeneration of lens from iris in organ culture. We have previously defined a critical period for the retinal influence in vivo and in vitro, and have shown that crude extracts of retina can enhance regeneration of lenses in culture (Connelly et al., J. Exp. Zool., 240:343-351, 1986). In this paper, we report on the lens regeneration enhancing activity (LRA) of more highly purified fractions of the retinal extracts. Heparin-sepharose chromatography of the crude retinal extract yields three fractions (Courty et al., Biochemie 67:265-269, 1985) called EDGF I, II, and III. EDGF I and II have affinity for heparin, while EDGF III does not. In our bioassay, LRA appears only in the EDGF III fraction. Dialysis of EDGF III against 0.1 N acetic acid yields a fraction which has affinity for cibacron blue sepharose (eluting at 2.15 M salt) and also has significant LRA. Because insulin at high doses has a marginal effect on lens regeneration in culture (Williams and McGlinn, Am. Zool. 19:923, 1979; Connelly, Differentiation 16:85-91, 1980), we tested IGF-I. Because of the putative neurotrophic effects of transferrin (Tf) (Mescher and Munaim, J. Exp. Zool., 230:485-490, 1986), we tested Tf for its ability to enhance regeneration of the lens in culture. IGF-I seems to have an enhancing effect on lens regeneration; Tf does not.

Animals↗
PubMed1991

Expression of the 9G1 antigen in the apical cap of axolotl regenerates requires nerves and mesenchyme.

Monoclonal antibody 9G1 (mAb 9G1) is reactive to the wound epithelium of axolotl larvae and therefore provided the opportunity to examine the interaction between the wound epithelium, nerves, and blastemal mesenchyme during axolotl limb regeneration. In unamputated limbs, mAb 9G1 is reactive to most or all cells of the dermis, skeletal elements, blood vessels, and nerves, to a few unidentified cells in muscle, and to none in epidermis. During regeneration of axolotl limbs, mAb 9G1 reacts strongly to an intracellular antigen of the blastemal mesenchyme and of the distal-most portion of the wound epithelium, the so-called apical epithelial cap (AEC). Because this thickened wound epithelium of regenerating amphibian limbs has been suggested as functioning in a manner similar to the apical ectodermal ridge (AER) of embryonic limb buds, it was of interest to further examine the reactivity of mAb 9G1 during various stages of regeneration. Whether mAb 9G1 reactivity in the AEC depended on mesenchyme and/or nerves was also tested. Monoclonal antibody 9G1 reactivity appears in the AEC of regenerating limbs prior to outgrowth of the blastema and persists throughout blastemal stages. Apical epithelial cap reactivity to mAb 9G1 is nerve dependent during early stages of blastema development and becomes nerve-independent at later stages. When epithelium-free blastemal mesenchyme is grafted onto injured flank musculature, ectopic limb regeneration occurs and the AEC derived from flank epidermis exhibits mAb 9G1 reactivity. These results show that a mAb 9G1 reactive AEC is characteristic of regenerating limbs and that expression of the 9G1 antigen by the AEC is dependent upon underlying blastemal mesenchyme and nerves.

Ambystoma mexicanum↗
PubMed1991

Early innervation of skeletal muscle during tail regeneration in urodele amphibians.

The innervation pattern of skeletal muscles was studied in the normal and regenerating tail of Notophthalmus viridescens. Silver staining for nerve endings and histochemical localization of acetylcholinesterase (AChE) were used for light microscopy. In In normal musculature, AChE positive reactions were localized at the ends of the muscle fibers where they are anchored on connective tissue septa by myotendinous junctions. At this level, silver staining shows nerve terminals forming endplates. During regeneration, positive reactions for AChE appear de novo as dense plates localized at the ends of the newly formed myotubes. The mechanisms involved in the localization of AChE on this surface seem to operate before previous local contacts by nerve terminals. From the ultrastructural data and immunohistochemical results with anti-laminin antibody, these observations suggest that regenerating muscle fibers determine a region of post-synaptic specialization in close relation with the organization of myotendinous regions and basement membrane formation. Nerve-muscle contacts appear at these levels at stage IV (15-20 days after amputation) in the stump and in the rostral part of the regenerate (transition zone). These nerve terminals are provided by the disorganized peripheral nervous system of the injured segment. In the regenerate a similar pattern of AChE reaction can be seen in every myotube, differentiating according to a rostro-caudal gradient. Innervation at the ends of the muscle fibers is in spatiotemporal relation with the exists of the ventral roots from the regenerating nerve cord as the regenerate continues to grow in length.

Animals↗
PubMed1992

Epimorphic vs. tissue regeneration in Xenopus forelimbs.

Postmetamorphic froglets of Xenopus laevis regenerate hypomorphic unbranched spikes from amputated arm stumps. These are composed primarily of cartilage, produced from blastemalike structures sparsely populated with cells and rich in connective tissue. Some consider these outgrowths to be an example of epimorphic regeneration produced from blastemas, albeit deficient ones. Others interpret them as a case of tissue regeneration derived from fibroblastemas augmented by chondrocytes and periosteal and perichondrial fibroblasts. To resolve these alternatives, forelimbs were amputated proximal to the wrist, skinned, and inserted through the body wall into the abdominal cavity. In the absence of skin, epidermal wound healing failed to occur and blastemas could not develop. After 2 months, by which time controls had regenerated spikes averaging 3.38 mm long, the denuded stumps had not given rise to outgrowths. They typically developed cartilaginous caps on the severed ends of the radius-ulna, and in rare cases formed amorphous growths of cartilage. If blastema formation is considered diagnostic of epimorphic regeneration and tissue regeneration can proceed in the absence of epidermal wound healing and blastema formation, these findings lead to the conclusion that Xenopus limb regeneration is epimorphic.

Animals↗
PubMed1992

The problem of the number of tarsomeres in the regenerated cockroach leg.

There are 5 tarsomeres in the normal cockroach leg, but this number is often reduced in regenerated legs. In order to examine this complicated situation, fore-, mid-, and hindlegs of German cockroaches were amputated at 11 different tarsal levels and at 18 different times during the last instar. When tarsi were amputated at or proximal to the 3rd tarsomere, 4-segmented tarsi regenerated. When legs were amputated distal to the 3rd tarsomere, the regenerated tarsi had 5 segments. Three-segmented tarsi rarely regenerated when legs were amputated proximal to 3rd tarsomere and in the latter half of the instar period. The lengths of all tarsomeres of regenerated tarsi were measured together with those of unoperated contralateral tarsomeres, and the ratios of the former to the latter were calculated. The ratios ranged from 28 to 138% for the various tarsomeres and levels of amputation. From a comparison of the ratios and morphological observations, it was suggested that the 3rd tarsomere of the normal 5-segmented tarsus has disappeared in the regenerated 4-segmented tarsus. Pads and disto-lateral spines of tarsomeres were observed on unoperated and regenerated tarsi. It was of interest that double spines were often found on the 4-segmented tarsi, mostly on the 2nd tarsomere, just proximal to the position of the missing 3rd tarsomere. This observation supported the idea that the 3rd tarsomere has not simply disappeared, but has probably fused with the 2nd tarsomere.

Animals↗
PubMed2002

Glial cell line-derived neurotrophic factor released by synthetic guidance channels promotes facial nerve regeneration in the rat.

Regeneration of the human facial nerve after lesion is often limited, leading to severe functional impairments, in particular when repair is delayed for several months, when cross-facial nerve grafts have to be performed, or in elderly patients. To improve the outcome, the potential accelerating and maturating effects of the neurotrophic factors glial cell line-derived neurotrophic factor (GDNF) and neurotrophin-3 (NT-3) on nerve regeneration were assessed using an axotomy model of the rat facial nerve. One-centimeter-long synthetic guidance channels releasing the neurotrophic factors over several weeks were used to bridge an 8 mm nerve gap, a distance that does not allow regeneration in the absence of growth factors. Nerve cables regenerated in the presence of GDNF showed a large number of myelinated axons 6 weeks after grafting (871 +/- 373, n = 5), whereas only 106 +/- 86 (n = 5) myelinated axons were counted in the presence of NT-3. Retrograde labeling with fluorogold revealed 981 +/- 450 (n = 5) and 53 +/- 38 (n = 5) retrogradely labeled motoneurons in the facial nucleus in the presence of GDNF and NT-3, respectively. No regenerated axons or retrogradely labeled cells were observed in the absence of growth factors (n = 6). These results demonstrate that GDNF, as previously described for the sciatic nerve, a mixed sensory and motor nerve, is also very efficient in promoting regeneration of the facial nerve, an essentially pure motor nerve. GDNF may therefore be useful in improving facial nerve regeneration in the clinic.

Animals↗
PubMed1993

Congruity of acetylcholine receptor, acetylcholinesterase, and Dolichos biflorus lectin binding glycoprotein in postsynaptic-like sarcolemmal specializations in noninnervated regenerating rat muscles.

Noninnervated regenerating muscles are able to form focal postsynaptic-like sarcolemmal specializations either in places of the former motor endplates ("junctional" specializations) or elsewhere along the muscle fibers (extrajunctional specializations). The triple labeling histochemical method was introduced to analyse the congruity of focalization in such specializations of 3 synaptic components: acetylcholinesterase (AChE), acetylcholine receptor (AChR), and a specific synaptic glycoprotein which binds Dolichos biflorus lectin (DBAR). Noninnervated regenerating soleus and extensor digitorum longus (EDL) muscles of the rat were examined and compared with denervated muscles of neonatal and adult rats. All junctional sarcolemmal specializations in noninnervated regenerating muscles accumulated AChE and AChR. Localization of the 2 components was identical within the limits of resolution of the method. DBAR could not be demonstrated in junctional specializations in 17-day-old regenerating muscles. It seems that an agrin-like inducing substance in the former junctional basal lamina invariably triggers the accumulation of both AChE and AChR in the underlying sarcolemma of the regenerating muscle fiber. However, accumulation of DBAR would probably require the presence of the motor nerve. In most of the extrajunctional sarcolemmal specializations in 8-day-old regenerating soleus and EDL muscles, both AChE and AChR accumulated. However, about 10 percent of AChE accumulations lacked AChR and about 35% of AChR accumulations lacked AChE. Even greater variability was observed in 17-day-old regenerating muscles. The presence of DBAR in the extrajunctional postsynaptic-like sarcolemmal specializations could not be demonstrated. Similar extrajunctional sarcolemmal specializations were observed in denervated postnatal rat muscles. About 70% contained both AChE and AChR, and 30% contained only AChR, but none contained DBAR. In denervated mature muscles, sparse extrajunctional AChR accumulations did not contain detectable amounts of AChE. The ability to form complex postsynaptic-like sarcolemmal specializations in the absence of nerve, which is probably inherent to noninnervated immature muscle fibers, may be reduced with muscle maturation. Variable accumulation of individual components in the postsynaptic-like specializations indicates that different triggering factors may be involved in their accumulation or, at least, the mechanisms of their accumulation can function relatively independently.

Acetylcholinesterase↗
PubMed2002

Bimodal dose-dependence of FK506 on the rate of axonal regeneration in mouse peripheral nerve.

FK506 has been shown to enhance the rate of axonal regeneration after peripheral nerve lesions. However, quite variable doses of FK506 have been used in different animal studies. We examined the dose-dependence of FK506 on the rate of axonal regeneration after crush lesion of the mouse sciatic nerve. Mice received daily subcutaneous injections of FK506 at 0.2, 0.5, 1, 2, 5, or 10 mg/kg for 7 days after lesioning. A control group was injected with saline. The distance that regenerative axons advanced from the crush site was measured by the pinch test at 2, 4, and 7 days. Regenerating axons reached greater mean distances in all FK506-treated groups compared to the control group. The fastest regeneration rate was found at 5 mg/kg (12% increase over controls), although the 0.2 and 2 mg/kg doses achieved similar regeneration rates. In contrast, intermediate doses (0.5 and 1 mg/kg) and a higher dose (10 mg/kg) were not different from controls. Calcitonin gene-related peptide immunohistochemical labeling of regenerating axons yielded similar results to those found with the pinch test. Based on our finding of a double peak in the dose-response for FK506, it is hypothesized that at least two mechanisms of action (perhaps corresponding to distinct functional binding sites) are evoked at different concentrations of the drug to accelerate nerve regeneration. These results have clinical implications for the pharmacological treatment of nerve injuries while avoiding immunosuppressive effects and for the design of related drugs with more specific activities.

Animals↗
PubMed1991

Basal lamina and superfast myosin expression in regenerating cat jaw muscle.

We investigated the possible role of extracellular matrix in specifying the expression of superfast myosin during cat jaw muscle regeneration. Equal proportions of muscle tissue from jaw and limb were minced together after killing cellular elements from one source. We allowed the mince to regenerate in the bed of a fast limb muscle. Regenerates were analyzed immunocytochemically at 71 to 294 days after operation. Fibers in control regenerates containing live cells from both sources expressed fast, superfast or slow myosins, or a mixture of these myosins. In regenerates containing only one type of live cells, we detected only myosins appropriate to the live cells. Our results suggest that during regeneration the original extracellular matrix of jaw-closing or limb muscle is unable to specify the expression of superfast or fast myosins, respectively; they point to the cellular elements, probably the satellite cells, as determinants of muscle specificity during regeneration.

Animals↗