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PubMed1997

Calmodulin-related changes in microsomal membrane fluidity during liver regeneration.

Based on our previous findings on the modifying effect of calmodulin (CaM) on the physiochemical properties of biomembrane, we have investigated the possible relationship between intracellular CaM content and endoplasmic reticulum (ER) membrane fluidity and function during liver regeneration. The degree of ER membrane fluidity was estimated by fluorescence polarization analysis with the 1,6-diphenyl-1,3,5-hexatriene probe. Microsomal guanylate cyclase (GC) was used as a functional parameter. The kinetics of the increase in the ER membrane fluidity during liver regeneration was strictly parallel to the CaM surge and was matched by an increase in GC activity. The stimulative effect of splenectomy on liver regeneration and its inhibition by Walker-256 tumor, inferred from the corresponding alterations of CaM levels, were mirrored by the modulation in GC activity. The fluidizing effect of CaM on ER membrane was concluded from the drop in thermotropic transition temperature from 28.3 +/- 1.6 degrees C in control membranes to 17.8 +/- 1.1 degrees C membranes from regenerating livers and to 19.8 +/- 1.2 degrees C in control membranes treated with CaM. Arrhenius plots of GC activity exhibited a transition temperature of 25.5 +/- 1.25 degrees C in controls, which shifted to 20.5 +/- 0.9 degrees C in ER membranes from regenerating livers and to 21.7 +/- 1.1 degrees C in control membranes treated with CaM. The Hill coefficient for the allosteric activation of the GC by Mn.GTP decreased from 1.49 +/- 0.16 in controls to 0.93 +/- 0.085 in membranes from regenerating cells and to 0.86 +/- 0.073 in CaM-treated membranes. Both effects of CaM were consistent with a fluidity increase in the enzyme's lipid microenvironment. The results of the present study suggest that an early key event in liver regeneration may be the CaM-induced modulation of ER membrane fluidity and function.

Animals↗
PubMed1999

Phenobarbital in comparison with carbon tetrachloride and phenobarbital-induced cirrhosis in rat liver regeneration.

BACKGROUND: The simultaneous administration of carbon tetrachloride (CCl4) and phenobarbital in the rat produces one of the most common experimental models of liver cirrhosis. As phenobarbital also has a hepatotrophic effect, its role in liver regeneration following partial hepatectomy (HTX) is not elucidated. PURPOSE: To examine the effect of long-term administration of phenobarbital in liver regeneration after HTX with regard to CCl4-induced cirrhotic rat model. Materials and Methods. The liver regeneration following HTX in phenobarbital-treated rats (PB rats) was compared to that seen in cirrhotic rats (LC rats), induced by oral gavage of CCl4 and phenobarbital, and normal rats. The effect of the withdrawal of phenobarbital was also examined. Liver regeneration was estimated 24 h after the HTX by measuring the liver weight, the DNA content in the liver, and [3H]thymidine incorporation into the DNA. RESULTS: Treatment with CCl4 and phenobarbital caused liver deformity, and the highest percentage of liver weight regeneration was seen in LC rats with this deformity, even though [3H]thymidine incorporation into the DNA was impaired in this group. Phenobarbital had a hepatotrophic effect, but its withdrawal caused a decrease in liver mass and cessation of body weight gain. The change in the DNA content 24 h after HTX was negative in PB rats. CONCLUSIONS: Liver regeneration could not be estimated using liver or body weight in the PB or LC rat model. [3H]Thymidine incorporation into the DNA was reliable indicator of liver regeneration in the different liver states during the early stage after HTX. Although the DNA content with respect to total liver mass was obscured due to liver inflation in PB rats, [3H]thymidine incorporation into the DNA between PB rats and normal rats was similar.

Animals↗
PubMed2002

Increased intraabdominal pressure impairs liver regeneration after partial hepatectomy in rats.

BACKGROUND: There are many experimental studies showing that increased intraabdominal pressure (IAP) reduces liver blood flow, leading to ischemia and portal venous congestion. But, there is no study evaluating the effect of increased IAP on liver regeneration. It is well known that acute liver ischemia and portal venous congestion impair liver regeneration. We, therefore, aimed to determine the effect of increased IAP on liver regeneration in this study. METHODS: Sprague-Dawley rats underwent partial hepatectomy with or without IAP of 12-14 mm Hg for 24 h or sham operation. Rats were randomly divided into six groups: two sham-operated groups, two hepatectomy groups, and two hepatectomy with increased IAP groups. Mitotic index, proliferating cell nuclear antigen (PCNA)-labeling index, and liver regeneration rate as liver regeneration parameters were studied on day 1 or on day 4 after operation. Additionally, serum aspartate transaminase (AST) level and histopathological changes in intestinal mucosa were studied. RESULTS: Hepatectomy with/without increased IAP groups had significantly higher serum AST levels than the sham-operated group on day 1. Serum AST level was found to be significantly higher in the hepatectomy with increased IAP group than in the other groups on day 4. Intestinal mucosal injury was found in the hepatectomy with increased IAP groups on days 1 and 4. Mitotic index and PCNA-labeling index were markedly higher in all hepatectomy with/without increased IAP groups than in the sham-operated groups. However, together with liver regeneration rate, both indices were significantly less in the hepatectomy with increased IAP groups than in the hepatectomy groups both on day 1 and on day 4. CONCLUSION: Maintenance of IAP between 12 and 14 mm Hg for 24 h impaired liver regeneration after partial hepatectomy in rats.

Abdomen↗
PubMed2001

Spinal cord repair: strategies to promote axon regeneration.

Neurons in the central nervous system have a remarkable capacity to regenerate their transected axons when provided with an appropriate growth environment. Advances in our understanding of axon regeneration have allowed the development of different experimental strategies to stimulate axon regeneration in animal models of spinal cord injury. Growth inhibitory proteins block axon regeneration in the CNS, and many of these proteins have been identified. Various methods that are now used to stimulate regeneration in the injured spinal cord are directed at overcoming the growth inhibitory environment of the CNS. Three general approaches tested in vivo stimulate regeneration in the spinal cord. First, antibodies that bind inhibitory proteins in myelin allow axon regeneration in the CNS. Second, methods that modulate neuronal intracellular signaling allow axons to grow directly on the inhibitory substrate of the CNS. Third, transplantation of cells to the lesioned spinal cord promotes repair. In this paper we review current advances in each of these research domains.

Animals↗
PubMed2004

Amphibian regeneration and stem cells.

Larval and adult urodeles and anuran tadpoles readily regenerate their limbs via a process of histolysis and dedifferentiation of mature cells local to the amputation surface that accumulate under the wound epithelium as a blastema of stem cells. These stem cells require growth and trophic factors from the apical epidermal cap (AEC) and the nerves that re-innervate the blastema for their survival and proliferation. Members of the fibroblast growth factor (FGF) family synthesized by both AEC and nerves, and glial growth factor, substance P, and transferrin of nerves are suspected survival and proliferation factors. Stem cells derived from fibroblasts and muscle cells can transdifferentiate into other cell types during regeneration. The regeneration blastema is a self-organizing system based on positional information inherited from parent limb cells. Retinoids, which act through nuclear receptors, have been used in conjunction with assays for cell adhesivity to show that positional identity of blastema cells is encoded in the cell surface. These molecules are involved in the cell-cell signaling network that re-establishes the original structural pattern of the limb. Other systems of interest that regenerate by histolysis and dedifferentiation of pigmented epithelial cells are the neural retina and lens. Members of the FGF family are also important to the regeneration of these structures. The mechanism of amphibian regeneration by dedifferentiation is of importance to the development of a regenerative medicine, since understanding this mechanism may offer insights into how we might chemically induce the regeneration of mammalian tissues.

Amphibians↗
PubMed2002

Radiation and regeneration: behavioral improvement and GDNF expression after Gamma Knife radiosurgery in the 6-OHDA rodent model of hemi-parkinsonism.

BACKGROUND: Recent research has demonstrated that the adult mammalian CNS is capable of regeneration. This regeneration is often initiated as a response to thermal, chemical or mechanical injury. The effects of radiation on the mammalian CNS have also been found to aid in certain regeneration processes. METHOD: In our project we examined the potential therapeutic value of radiation induced regeneration of diseased mammalian rat CNS. Eleven Sprague-Dawley rats with 6-hydroxy-dopamine (6-OHDA) induced hemi-parkinsonism were treated in the Leksell Gamma Knife using a single 4 mm collimator shot targeted to the ipsilateral (parkinsonian) caudate-putamen complex. A maximum dose of 140 Gy was used to create a necrotic lesion. Animals were tested behaviorally using the apomorphine-induced rotational behavior model before and up to 6 months after radiosurgery. Histochemical analysis was performed 2 weeks, 1 month and 4 months after radiosurgery. Histological sections were obtained and immunohistochemistry was performed for glial cell line derived neurotrophic factor (GDNF). FINDINGS: The rotational behavior for 11/11 animals (100%) was found to initially worsen at 2 weeks and 4 weeks after radiosurgery before a statistically highly significant reduction in apomorphine induced rotations was observed at 2, 3, and 4 months after radiosurgery (83% reduction by month four; p < 0.0001). For 2/11 animals the rotational behavior almost disappeared indicating near-abolition of parkinsonian behavior. On histological examination, the lesions were easily identified as areas of necrosis about 4 mm in diameter. The region immediately adjacent to the lesion was found to have highly positive expression of GDNF indicating high activity in dopamine-regenerating processes. INTERPRETATION: In this preliminary study we demonstrated that radiosurgical lesioning with the Gamma Knife into the striatum of hemi-parkinsonian animals resulted in significant behavioral improvement of signs of parkinsonism. Since GDNF expression is tightly linked to the dopaminergic system, we conclude that focused radiation is potentially capable of inducing regeneration of dopaminergic pathways in the adult CNS. Further studies with dose deescalation and molecular biological characterization of the regeneration cascades are necessary to gain access to potential clinical value of our observations.

Animals↗
PubMed1996

Adaptive range of myosin heavy chain expression in regenerating soleus is broader than in mature muscle.

In adult rat muscles experimentally exposed to various patterns of activation, expression of myosin heavy chain isoforms changes, but only within a certain adaptive range. It is characteristic and different in fast or slow muscles. This may be due either to different intrinsic properties of the myogenic cells of the two types of muscles or to extrinsic factors. To test these assumptions, either rat soleus or extensor digitorum longus muscles were injured and transplanted to the bed of the extensor digitorum longus muscle. They regenerated and were reinnervated by the extensor digitorum longus nerve. Expression of myosin heavy chain isoforms was demonstrated immunohistochemically and by in situ hybridization, and analysed by SDS-gel electrophoresis. Three months after cross-transplantation, regenerated soleus expressed all adult myosin heavy chain isoforms, including the myosin heavy chain-2B. The latter was detected in about 50% of muscle fibres and contributed about 10-20% of all myosin heavy chains. The same percentage of myosin heavy chain-2B was found in regenerated extensor digitorum longus. In this regard therefore, the adaptive range of the regenerated soleus muscle was not significantly different from that of the extensor digitorum longus regenerating under the same conditions. This indicates that restriction of the adaptive range in a mature soleus muscle is not due to intrinsic properties of its myogenic cells. It is probably imposed by an extrinsic factor leading to irreversible shut-down of individual myosin heavy chain genes. On the other hand, myosin heavy chain-1 expression was significantly greater in the regenerated soleus than in the extensor digitorum longus innervated by the same nerve. Myosin heavy chain-1 and myosin heavy chain-2B were co-expressed in some regenerated soleus muscle fibres.

Animals↗
PubMed1992

Displaced retinal ganglion cells in normal frogs and those with regenerated optic nerves.

We have analysed the number and spatial distribution of displaced retinal ganglion cells in the frog Litoria (Hyla) moorei. A series of normal animals was compared with one in which the optic nerve was crushed and allowed to regenerate. Ganglion cells were labelled with horseradish peroxidase (HRP) applied to the optic nerve, and retinae were examined as sections or whole mounts. We analysed separately ganglion cells with somata displaced to the inner nuclear (Dogiel cells, DGCs) and to the inner plexiform layer (IPLGCs). These findings were related to data for the orthotopic ganglion cells (OGCs). The mean number of DGCs in the normal series was 2,550 (+/- 281) and fell to 1,630 (+/- 321) after regeneration, representing a mean loss of 36%. This reduction was not significantly different from the mean loss of 43% from the OGC population in which mean values fell from 474,700 (+/- 47,136) to 268,700 (+/- 54,395). In both the normal and the regenerate series, DGCs were estimated to represent means of only 0.6% of the OGC population. Densities of DGCs were highest in the naso-ventral and temporo-dorsal peripheries; densities of both DGCs and OGCs were lower after optic nerve regeneration. We conclude that the factors which affect ganglion cell death during optic nerve regeneration, do so to similar extents amongst the DGC and the OGC populations. The IPLGCs were very rare in normal animals with a mean of 420 (+/- 95). However, their numbers increased after regeneration to a mean of 3,350 (+/- 690), estimated to be 1.2% of the OGC population. These cells normally favoured peripheral retina but became pan-retinal after regeneration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Involution and regeneration of the endometrium following parturition in the ewe.

Involution and regeneration of the endometrium after parturition in the ewe, were studied by light- and electron microscopy. The luminal epithelium in intercaruncular regions of the endometrium remained intact at all stages, but degeneration and death of many glandular epithelial cells were observed on the day after parturition. Glandular regeneration had commenced by 8 d post partum, and the glands were substantially regenerated by 15 d. Caruncular epithelial cells on the maternal side of the placentomes, between the bases of the maternal septa, persisted during the period of degeneration of the foetal and maternal tissues of the placentomes. Epithelial cells from this source contributed to the regeneration of the caruncular epithelium following shedding of plaques of degenerate placental tissue from the caruncles, which commenced after 8 d and was completed before 31 d. Thus, ingrowth of epithelium from the edges of the caruncles, as previously proposed, was not the sole source of new caruncular epithelium. The additional source of regenerating epithelium identified here may account for the rapidity with which epithelium appears in the centres of some caruncles, several millimetres in diameter, during endometrial regeneration. However, in some caruncles, regeneration of the epithelium was not completed until after 31 d post partum.

Animals↗
PubMed1982

Morphological study on the regeneration of the retina in the rainbow trout after ouabain-induced damage: evidence for dedifferentiation of photoreceptors.

The retina of the rainbow trout is capable of marginal regeneration after ouabain-induced degeneration (intraocular injection of 5 microliters 10(-4) M ouabain). In the central area where the pigment epithelium proliferates to a multicellular layer, the neural retina does not regenerate up to 182 days after injection of ouabain. The regeneration process begins in the marginal growth zone with an increase in the mitotic rate; the growth zone itself is not damaged after ouabain administration. The proliferate differentiates with time into a newly layered retina; this portion of the retina is called the paramarginal zone, i.e., the "first" regenerated zone. The paramarginal zone is arranged concentrically to the retinal margin. Cells surviving ouabain administration, located outside, although close to the margin and occurring mostly in the outer nuclear layer, reveal signs of dedifferentiation: loss of the outer segment, amalgamation of the presynaptic terminal with the perikaryal cytoplasm, alteration of cell shape, and mitotic activity. The area in which these dedifferentiation processes are observed is found adjacent and concentric to the paramarginal zone; it is thinner than the latter and incompletely structured ("second" regenerated zone). The third zone adjoins the second zone and is characterized by folds, which were described previously as "rosettes". Extracellular microtubule-like structures, which are found between the horizontal cells in the normal retina of the rainbow trout, regenerate only sparsely in the paramarginal zone, whereas they are lacking in the incompletely regenerated zones.

Animals↗
PubMed1978

Regeneration of the vallate papilla in the rat with special reference to the origin of the taste bud-bearing epithelium.

The regeneration of the vallate papilla in the rat was studied by both light and electron microscopy. The papillae were excised and regeneration was studied at time intervals of 3 to 45 days. It was found that the vallate papilla is capable of regeneration after both partial and total papillectomies. The regenerated papillae were asymmetrical in shape. Several invaginations, independent of one another, were the equivalent of the original sulcus. Regeneration of the gustatory system occurred at circumscribed portions of the associated Von Ebner glands. The amounts of newly formed taste buds were proportional to the amount of nerve fibers in the subepithelial plexus. The regenerated taste buds showed normal histochemical and fine-structural characteristics. The results support the contention of some degree of specificity concerning the epithelium where taste bud regeneration occurs.

Animals↗
PubMed1984

Messenger RNA in regenerating liver: implications for the understanding of regulated growth.

The application of nucleic acid hybridization techniques to the study of liver regeneration has led to a revision of some well-established ideas about the patterns of gene expression during regenerative growth. This paper focuses on two broad problems: a) the extent to which mRNA populations in regenerating liver differ qualitatively or quantitatively from those of normal liver, and b) the similarities and differences between the pattern of gene expression during liver regeneration and liver development. Answers to these questions have come from studies in normal and regenerating liver of, a) the proportion of non-repetitive and repetitive DNA transcribed, b) the complexity of mRNA populations and the abundance of sequences in these populations, c) the extent of homology between mRNA populations, d) the amounts of specific mRNAs for albumin, alphafetoprotein, and fibrinogen, and e) the transcription of some cellular oncogenes. Changes in the abundance of liver mRNA transcripts, without major qualitative alterations in the spectrum of sequences contained in the RNA populations, are sufficient to permit the transition of hepatocytes from a resting into a dividing state. Transcripts from at least two cellular oncogenes are included among the mRNA sequences which become more abundant during liver regeneration. Analysis of the expression of some specific genes (albumin, alphafetoprotein and fibrinogen) during liver regeneration suggests that there is little similarity between the patterns of gene expression in regenerating and developing liver.

Albumins↗
PubMed1991

Labelling of regenerating retinal pigment epithelium by colloidal iron oxide and ferritin conjugated to wheat germ agglutinin.

In order to determine if there are biochemical changes in plasma-membrane oligosaccharides of regenerating retinal pigment epithelium, the binding of colloidal iron oxide at low pH and ferritin-conjugated wheat germ agglutinin--probes of sialic acid and N-acetylglucosamine on the cell surface--was examined electron-microscopically. An animal model of retinal pigment epithelium regeneration--rabbits with sodium iodate induced retinopathy--was used. In this model, large expanses of regenerating pigment epithelium are present for comparison with zones of spared pigment epithelium in the same animals. In thin sections examined by transmission electron microscopy, ferritin-conjugated wheat germ agglutinin appeared to bind more intensely to the exposed plasma membrane of regenerating retinal pigment epithelium than to spared pigment epithelium, or that of normal rabbits. Morphometry verified this. Colloidal iron oxide intensely labelled the plasma membranes of regenerating, spared, and normal pigment epithelium, and was visibly reduced after exposure of tissue to neuraminidase. The observations indicate that the plasma membrane of regenerating retinal pigment epithelium bears sialic acid and N-acetylglucosamine residues as in normal retinal pigment epithelium. However, the amount of plasma membrane bearing exposed N-acetylglucosamine increases during regeneration.

Animals↗
PubMed1990

Nerve regeneration through the cryoinjured allogeneic nerve graft in the rabbit.

To examine whether the 3-4-cm-long allogeneic basal lamina tubes of Schwann cells serve as conduits for regenerating axons in rabbits, allogeneic saphenous nerve, which had been predenervated and pretreated by freezing, were transplanted from Japanese White rabbits (JW) to New Zealand White rabbits (NW). Animals were killed 1, 2, 6, 8, and 14 weeks after transplantation, and the cytology at the mid-portion of the grafts was examined by electron microscopy. The distal portion of the host saphenous nerves was also examined 14 weeks after grafting. Myelin sheath debris was phagocytosed by macrophages, while the basal lamina of Schwann cells were left intact in the form of tubes. Regenerating axons were first found in such basal lamina tubes 2 weeks after grafting, and gradually increased in number. Host Schwann cells accompanied the regenerating axons behind their growing tips, separating them into individual fibers and forming thin myelin sheaths on thick axons by 6 weeks after grafting. Regenerating nerves were divided into small compartments by new perineurial cells. Newly formed blood vessels were situated outside the compartment 8 weeks after grafting. The percentage of myelinated fibers in the regenerating nerves was roughly 10% at 8 weeks and 30% at 14 weeks after grafting. The diameter of the regenerating axons, both myelinated and unmyelinated, was less than that of normal axons at all the stages examined. Numerous regenerating axons, some of which were fully myelinated, were found at the site 10 mm distal to the distal end of the graft 14 weeks after grafting.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Innervation of regenerated spindles in muscle grafts of the rat.

Features of the nerve supply and the encapsulated fibers of muscle spindles were assessed in grafted and normal extensor digitorum longus (EDL) muscles of rats by analysis of serial 10-microns frozen transverse sections stained for enzymes which delineated motor and sensory endings, oxidative capacity and muscle fiber type. The number of fibers was significantly more variable, and branched fibers were more frequently observed in regenerated spindles than in control spindles. Forty-eight percent of regenerated spindles received sensory innervation. Spindles reinnervated by afferents had a larger periaxial space than did spindles which were not reinnervated by afferents. Regenerated fibers innervated by afferents had small cross-sectional areas, equatorial regions with myofibrils restricted to the periphery of fibers, unpredictable patterns of nonuniform and nonreversible staining along the length of the fiber for 'myofibrillar' adenosine triphosphatase (mATPase) after acid and alkaline preincubation. In contrast, regenerated fibers devoid of sensory innervation resembled extrafusal fibers in that they usually exhibited myofibrils throughout the length of the fiber, no central aggregations of myonuclei, uniform staining for mATPase and a reversal of staining for mATPase after preincubation in an acid or alkaline medium. Approximately thirty percent of encapsulated fibers devoid of sensory innervation stained analogous to a type I extrafusal fiber, a pattern of staining never observed in intrafusal fibers of normal spindles. Groups of encapsulated fibers all exhibiting this pattern of staining reflect that either these fibers may have been innervated by collaterals of skeletomotor axons that originally innervated type I extrafusal fibers or that fibers innervated by only fusimotor neurons express patterns of staining for mATPase similar to extrafusal fibers in the absence of sensory innervation. Sensory innervation may also influence the reestablishment of multiple sites of motor endings on regenerated intrafusal fibers. Those regenerated fibers innervated by afferents had more motor endings than did regenerated fibers devoid of sensory innervation. Differences in size, morphology, and patterns of staining for mATPase and numbers of motor endings between fibers innervated by afferents and fibers devoid of sensory innervation reflect that afferents can influence the differentiation of muscle cells and the reestablishment of motor innervation other than during the late prenatal/early postnatal period when muscle spindles form and differentiate in rats.

Adenosine Triphosphatases↗
PubMed1983

Regeneration and reinnervation of the dystrophic mouse soleus muscle. A light- and electron-microscopic study.

The regeneration and reinnervation of the dystrophic mouse soleus muscle was investigated in response to a double crush-lesion, which causes degeneration of muscle fibres leaving the innervation intact. In normal and dystrophic muscles, injury produced degeneration of muscle fibres, proliferation and fusion of muscle satellite cells, and growth and reinnervation of regenerating fibres. Four, 6 and 21 days after injury, regenerating dystrophic fibres were 50% smaller in cross-sectional area than regenerating normal fibres and showed several pathological changes. Nerve terminal morphology was initially unaffected by the crush, and nerve terminals were associated with degenerating muscle fibres 2 days after injury and with regenerating muscle fibres 6-28 days after crushing. In intact muscles dystrophic endplates were longer and showed increased ultraterminal sprouting compared to normal endplates. At 28 days after crushing normal nerve terminal sprouting was significantly increased compared to the contralateral control. The extent of nerve terminal sprouting and endplate length in dystrophic muscles was not affected by the degeneration and subsequent regeneration of the muscle fibres. We conclude that a proportion of dystrophic mouse soleus muscle fibres can regenerate after a crush when the innervation is left intact.

Animals↗
PubMed1984

The origin of muscle stem cells in rat triceps surae regenerating after mincing.

Rat triceps surae was minced and orthotopically autografted. Twitch time to peak, maxima tetanic tension, lactate dehydrogenase activity and total creatine concentration were measured in muscles regenerating for 30, 60 and 90 days. If the minces were frozen and thawed before grafting, muscle regeneration was suppressed. If they were further heated before grafting, muscle regeneration was also suppressed. If one half of the mince was either frozen and thawed or frozen, thawed and heated, and then recombined with the remaining half, muscle regeneration was delayed. However, at 90 days, 'intensive properties' (twitch time to peak, maximum tetanic tension, total creatine concentration and lactate dehydrogenase activity) of regenerates obtained from such partially treated minces were similar to those of regenerates obtained from untreated minces although their 'extensive properties' (weight and maximal tetanic force) were approximately halved. The extent of regeneration depends on the mass of untreated mince autografted and thus, presumably, on the number of viable muscle stem cells initially present in the mince.

Animals↗
PubMed1994

Astrocytes and axon regeneration in the central nervous system.

The failure of axons to regenerate in the central nervous system is mainly due to inhibition by the environment, made up of astrocytes and oligodendrocytes, which surrounds regions of damage. Both cell types are inhibitory to axon regeneration, and it seems likely that each will have to be neutralised before significant axon regeneration is achieved. Axons regenerate over the surface of astrocytes grown in normal monolayer culture but not through three-dimensional astrocyte cultures. Astrocyte cell lines have been created, some of which resemble embryonic astrocytes and form a loose tissue with extensive extracellular space which permits axon regeneration, and others which model astrocytes in the damaged brain having little extracellular space and much extracellular matrix material. There is no correlation between the inhibitory effect on axons and the expression of cell adhesion molecules, proteases, protease inhibitors, and a variety of extracellular matrix molecules. However, extracellular matrix produced by inhibitory cell lines is inhibitory to axon regeneration, while that produced by permissive cell lines is not. This difference depends on the production of a chondroitinase-sensitive proteoglycan which can block the neurite-inducing effects of laminin so that treatment of inhibitory extracellular matrix with chondroitinase renders it more permissive to axon regeneration.

Animals↗