A

FIGURE 4.5 Regeneration of skin in a pig excisional wound using a regeneration template consisting of non-denatured bovine collagen I plus elastin. (A) Diagram of operation. A grid is tattooed on the surface of the skin and a split-thickness skin graft is harvested. The remainder of the dermis is then removed to make a full-thickness defect. The regeneration template is inserted in the wound and covered by the meshed split-thickness skin graft. (B) Top, new skin regenerated using a native...

C Regeneration in the Adult Newt

Cells in the ciliary marginal zone (CMZ) of the newt eye proliferate throughout life to add new neurons of all types to the retina as the eye grows (Perron et al., 1998). These cells can be stimulated to proliferate after injury. However, the adult newt regenerates the retina primarily by dedifferentiation and transdifferentiation of RPE cells into a neuroepithelium that differentiates into the layers of the new retina (FIGURE 5.22), in the same way that PECs of the dorsal iris dedifferentiate...

Elsevier

AMSTERDAM BOSTON HEIDELBERG LONDON NEW YORK OXFORD PARIS SAN DIEGO SAN FRANCISCO SINGAPORE SYDNEY TOKYO Academic Press is an imprint of Elsevier Academic Press is an imprint of Elsevier 30 Corporate Drive, Suite 400, Burlington, MA 01803, USA 525 B Street, Suite 1900, San Diego, California 92101-4495, USA 84 Theobald's Road, London WC1X 8RR, UK This book is printed on acid-free paper. Copyright 2006, Elsevier Inc. All rights reserved. No part of this publication may be reproduced or transmitted...

Cellular Events of Lens Regeneration in the Newt

Figure 3.14 illustrates the stages of lens regeneration in the newt eye. Two days after lentectomy, there is an increase in the synthesis of ribosomal RNA by the amplification of rRNA genes and their increased rate of transcription (Reese et al., 1969 Collins, 1972). Dedifferentiation and proliferation begin by four days (Yamada and Roesel, 1969, 1971 Reyer, 1971). Expression of the c-myc proto-oncogene is enhanced in dedifferentiating PECs and proliferative activity is increased (Agata et al.,...

Introduction

The skin is the largest organ of the vertebrate body. Skin has many functions, including thermoregulation, sensory transduction, and acting as a mechanical barrier to protect the body from dessication, invasion by microorganisms, and environmental insults such as UV irradiation, mechanical trauma, and chemical or thermal burns. The preservation of normal skin structure, especially facial skin, has a high social value, since facial appearance and expression are such important determinants of...

Phases Of Repair In Excisional Wounds

Repair of an excisional skin wound can be divided into three tightly integrated phases that occupy variable time frames, depending on the size of the wound. These phases are hemostasis, inflammation, and structural repair (Kirsner and Eaglstein, 1993 Linares, 1996 Sicard et al., 1998 Yannas, 2001 Schultz et al., 2003). Each phase initiates and overlaps the next. The phase of structural repair can be divided into the formation of granulation tissue and the remodeling of granulation tissue to...

Norglia Lesions

Improvement was noted in the absence of FGF-1, indicating that this growth factor is essential for axon extension. A small number of human SCI patients have been treated with this experimental protocol. Cheng et al. (2004) reported that a patient who had suffered a thoracic SCI four years previously experienced motor and sensory improvements after receiving a graft of a sural nerve along with FGF-1 treatment. However, similar treatment of eight patients in Brazil (Tarcisio Barros, University of...

Acceleration of Acute Wound Repair by Topically Applied Agents

A wide variety of topical agents have been employed to accelerate the normal repair process and produce stronger scar tissue in acute wounds of normal skin. Application of healing accelerants as early as possible after wounding is desirable, because of the cascade effects that carry through to later stages of healing. TABLE 4.1 summarizes some of the many topical agents that have been used to accelerate the repair of wounded TABLE 4.1 Agents That Have Been Found, Singly or in Combination, to...

Axons of Amphibian Spinal Cord

Unlike mammals, larval and adult urodeles regenerate the axons of ascending and descending nerve tracts after transection or ablation of the spinal cord at the level of the trunk, with recovery of function (Piatt, 1955 Butler and Ward, 1965 Egar and Singer, 1972, 1981 Nordlander and Singer, 1978 Holder and Clarke, 1988 Chernoff et al., 2003 Ferretti et al., 2003). The ependymal (NSC) layer of the cord plays a central role in this process (Holder and Clarke, 1988 Ferretti et al., 2003 Chernoff...

C Remodeling of Granulation Tissue into Scar

In the final phase of structural repair, the granulation tissue is remodeled into a relatively acellular fibrous scar tissue (figure 2.4). The scar differs from normal dermis in several ways (Miller and Gay, 1992 Davidson et al., 1992 Linares, 1996). Fibronectin and HA levels return to normal, but the level of decorin PG is lower than in normal skin, and the level of chondroitin-4-sulfate PG is much higher. The organization of the ECM is also different. The number of elastin fibers is reduced...

Fibroblast Migration and Proliferation

The source of fibroblasts for structural repair appears to be two-fold, resident dermal fibroblasts and fibro-blasts differentiating from circulating mesenchymal stem cells from the bone marrow that enter the wound from the vasculature (Fathke et al., 2004). The marrow-derived fibroblasts synthesize both collagens I and III, whereas the resident fibroblasts synthesize only collagen I. The resident fibroblasts come primarily from the deep layers of the reticular dermis and the hypodermal...

Regeneration of Hippocampal Neurons

The hippocampus is an area of the brain that is crucial for cognitive activities, learning, and memory. Proliferating NSCs with long-term renewal potential have been identified in the hippocampus of mice and rats (Rao, 1999 Gage, 2000 Momma et al., 2000 Guena et al., 2001 Rietze et al., 2001), marmoset monkeys (Gould et al., 1998), and deceased human patients given BrdU as part of a cancer study (Eriksson et al., 1998). The precise location of hippocampal NSCs is still unclear. The dentate...

Induction of Regeneration In Situ

Although the initial objective of cell transplantation was the differentiation of the transplanted cells into new tissue that becomes integrated into the host tissue, there is substantial evidence that transplanted cells also secrete paracrine factors that are protective to host cells, promote their survival, proliferation, and differentiation, and suppress scarring. Thus, a third strategy of regenerative medicine is to identify these factors, or small molecules that mimic their action or...

Stimulation Of Hair Regeneration

Androgenetic alopecia, or male pattern baldness, is a genetic predisposition in which there is thinning and loss of the hair on the temples and crown of the scalp in an M-shaped pattern (Springer et al., 2003). The cause is sensitivity of hair follicles in these regions to the hormone dihydrotestosterone (DHT), which is formed in scalp cells from testosterone by the action of the enzyme 5-a-reductase. DHT acts to progressively shorten the anagen stage of hair growth while lengthening telogen,...

D Axon Elongation Factors

The same neurotrophins that enhance survival of axotomized neurons also enhance axon elongation (table 5.1), through their interaction with the p75NTR receptor (Davies, 2000). In the absence of neurotroph- TABLE 5.1 Soluble factors that are mitogenic for dedifferentiated Schwann cells and that are required for neuron survival and axon elongation after axotomy. These factors are produced by macrophages, platelets and the axons and Schwann cells themselves. Factors required for Neuron Survival...

W V

FIGURE 6.18 (A) A Trojan Horse strategy to allow a small bifunctional molecule to bind to a chaperone and gain the steric bulk required to disrupt amyloid P aggregation. One end of the bifunctional molecules binds to the FK506 binding protein, a member of the FKBP chaperone family of peptidyl prolyl cis-trans isomerases that are highly expressed in all mammalian cells. The other end of the bifunctional molecule interacts with AP to block aggregation. (B) One such bifunctional molecule is SLF...

Strategies Of Regenerative Medicine

Three main strategies are being used to develop clinical regenerative therapies (figure 1.7). These are cell transplantation, implantation of bioartificial tissue constructs (tissue engineering), and the chemical (pharmaceutical) induction of regeneration from tissue at the site of injury or recruited from elsewhere in the body. Which strategy is used depends on which is more appropriate for the nature of the tissue and the extent of the damage to be repaired. In general, cell transplantation...

Evolutionary Significance of Regeneration and Fibrosis

Wound repair and tissue regeneration are ubiquitous to multicellular organisms. These processes are universally adaptive, in that they are obligatory for the survival of multicellular organisms thus, natural selection will always favor them. Epimorphic regeneration, however, is restricted to only a relatively few species within each phylum. This fact is sometimes taken to mean that epimorphic regeneration arose in a few species from nonregenerating ancestors by selection for favorable mutations...

C Tissue Level

There are three prerequisites for regeneration at the tissue level. First, tissues must contain mitotically competent cells that is, cells that have the receptors and signal transduction pathways to respond to a regeneration-permissive environment. Second, the injury environment of the tissue must contain the necessary signals to promote the proliferation and differentiation of these cells in an organized way. Third, factors inhibitory to regeneration must be absent from the injury environment,...

Axons of Mammalian Spinal Cord

A cross-section of cat spinal cord is illustrated in FIGURE 5.7. In mammals, spinal cord injury that destroys substantial numbers of axons and neurons causes sensory deprivation and paralysis below the level of injury, followed by muscle atrophy, spasticity, and bone loss (McDonald and Sadowsky, 2002 Eser et al., 2004). Cervical injuries result in disturbances in autonomic functions such as regulation of blood pressure, heart rate, and temperature. The spinal cord of mammals contains NSCs in...

C Reduction of Scarring by Modulating the Inflammatory Response

A number of topical interventions that reduce the inflammatory response have been tried in an attempt to reduce scarring in adult skin wounds, particularly to reduce the presence of TGF-P1 and 2, or create a more fetal-like ECM. Hepatocyte growth factor (HGF) is an important growth factor in liver regeneration (Chapter 7). HGF has angiogenic, angioprotective, anti-inflammatory and antifibrotic activities (Matsumoto and Nakamura, 1996), but its expression has not been studied in healing skin...

Acellular Dermal Regeneration Templates

Bioartificial skin equivalents are cryopreserved until use, a procedure that may seriously reduce the viability of fibroblasts in the dermal component (Mansbridge et al., 1998). Thus, the dermal matrix of cryopreserved complete skin equivalents may actually be much less cellular when used than when they were constructed, or may even be acellular. The trend today is, in fact, toward the use of much less expensive acellular dermal templates overlaid with MSTSGs or cultured keratino-cytes to...

B Other Agents

Agents not known to be part of the normal wound repair pathways have also been found to enhance skin repair in a variety of ways. Several of these agents appear to work by enhancing the formation of granulation tissue. Extract of the Celosia argentea leaf, which has antimicrobial properties and is used in traditional medicine to treat skin conditions, has also been reported to accelerate normal wound repair in a rat burn model (Priya et al., 2004). Wound closure took place in half the time for...

Bm

FIGURE 5.13 Regeneration of olfactory sensory neurons (OSN). The basal layer of the olfactory epithelium (OE) consists of several cell types. The main type is the self-renewing globose basal stem cell (GBC). The GBC gives rise to immature olfactory sensory neurons (OSNi) which are closest to the surface of the epithelium. Another basal cell type is the self-renewing horizontal basal cell (HBC) that may also give rise to OSNi. OSNm mature OSN. Large sustentacu-lar (Sus) cells, which phagocytose...

Extracellular Matrix Synthesis by Fibroblasts

As fibroblasts invade the wound space, they replace the provisional fibrin matrix with an ECM consisting of Fn, HA, sulfated PGs and type I and III collagens (Miller and Gay, 1992 Weitzhandler and Bernfield, 1992). Hyaluronic acid predominates over Fn in early granulation tissue, opening up migration space for fibroblasts. Type III is the major collagen synthesized at this time (Whitby and Ferguson, 1991 Miller and Gay, 1992). The early appearance of type III collagen is associated with the...

Mammals Have Some Capacity for Lens Regeneration

Rabbits, cats, and mice can regenerate an imperfect lens if the lens is removed from the lens capsule, leaving the capsule behind (Gwon et al., 1990 Call et al., 2004). A new lens is formed by the proliferation and differentiation of residual lens epithelium cells that remain adherent to the lens capsule. Interestingly, in human cataract surgery to replace the lens with a plastic lens, the posterior, and part of the anterior, lens capsule is left behind to hold the artificial lens. Residual...

Info

TABLE 4.5 Effect of KGF2 administered topically twice per week for 12 weeks on healing of chronic venous ulcers in a subset of patients with wounds less than or equal to 15 cm2 and less than or equal to 18 months duration. Data expressed as the percentage of patients that showed 50-100 healing of wounds. KGF2 at 60 g cm2 was the most effective. Data from Robson et al. (2001) Percent of Wound Percentage of Subjects Healed_Placebo 20 g cm2 KGF2 60 g cm2 KGF2 in ischemic ear wounds, but a much...

Bv

FIGURE 5.2 Cross sectional organization of an individual spinal nerve. (A) The whole nerve is made up of fasicles (F) composed of endoneurial units (EU). An epineurium (EpN) surrounds the nerve. (B) Structure of an individual fascicle, surrounded by a perineurium (Pn). (C) Endoneurial unit. The axon (A) is myelinated (M) by wraps of Schwann cell (SC) plasma membrane. The endoneurium (En) synthesizes a basement membrane (BM). FIGURE 5.3 Entry of mixed spinal nerves into the spinal cord. Sensory...

Axons of Amphibian and Fish Optic Nerve

FIGURE 5.11 Effects of growth factors on explants of axolotl spinal cord tissue. (A, B) Medium containing TGF-P and EGF (TPE) supports ependymal outgrowth at 0 days (0D) and 6 days. (C-F) TGF-P (T) and PDGF (P) cause ependymal explants to break apart and disperse on the dish as cords of cells over a six-day period in culture. Courtesy of Dr. Ellen Chernoff. FIGURE 5.11 Effects of growth factors on explants of axolotl spinal cord tissue. (A, B) Medium containing TGF-P and EGF (TPE) supports...

B

FIGURE 5.9 Spinal cord regeneration in the axolotl, a urodele salamander. (A) Cord transection showing interruption of ascending and descending axon tracts red and black arrows). The spinal canal is lined by ependymal epithelial cells. These cells transform into mesenchymal cells (red) that proliferate to bridge the gap. The mesenchymal cells then transform back to epithelial cells to re-establish the ependyma and provide paths for axon regeneration. (B) Section showing mesenchymal cells two...

Summary

Regenerative therapies are available for acute and chronic skin wounds, hair loss, periodontal injuries and disease, and diseases and injuries of the cornea. A wide variety of topical agents have been tested for their efficacy in accelerating repair of acute wounds in normal skin. The growth factors TGF-P, FGF-2, EGF, GH, and IGF-1 can accelerate the repair of acute wounds in experimental animals. FGF-2 and GH have this effect in human patients. Other agents reported to accelerate the repair of...

Is Suvarna Gedde Good For Healing Wounds

Ashcroft GS, Dodsworth J, van Boxtel E, Tarnuzzer RW, Horan MA, Schultz GS, Ferguson WJ (1997) Estrogen accelerates cutaneous wound healing associated with an increase in TGF- 1 levels. Nature Med 3 1209-1215. Badylak SF, Coffey AC, Lantz GC, Tacker WA, Geddes LA (1994) Comparison of the resistance to infection of intestinal submucosa arterial autografts versus polytetrafluoroethylene arterial prostheses in a dog model. J Vasc Surg 19 465-472. Baker CA, Uno H, Johnson GA (1994) Minoxidil...

D Regeneration in the Bird

During optic cup formation in stage 9-10 embryos, the prospective RPE (outer layer of the optic cup) differentiates as neural retina if its contact with the prospective retina (inner layer of the optic cup) is broken (Orts-Lorca and Genis-Galvez, 1960), suggesting that RPE cells can transdifferentiate to retinal neurons and that the retina normally inhibits the RPE from differ- FIGURE 5.23 Induction of neural retina regeneration in chick embryos. (A) The neural retina is suctioned from a stage...

Cellular and ECM Differences Between Fetal and Adult Wound Healing

A number of differences have been noted between the repair of fetal and adult wounds. Scanning electron and confocal microscopy studies on amputated embryonic mouse (11.5 days of gestation) hindlimb buds in vitro indicated that re-epithelialization is complete by 24 hr (McCluskey and Martin, 1995). Re-epithelializa-tion occurs not by lamellipodal crawling (migration) of cells as in the adult, but by a purse-string contraction of a filamentous actin cable assembled in the basal layer of cells at...

Maintenance Regeneration a Interfollicular Epidermis

The epidermis of the mammalian skin is a continuous, multilayered epithelium interspersed with several appendages hair follicles, sebaceous glands, and sweat glands. The regions of epidermis between the hair follicles and their associated sebaceous and sweat glands are termed the interfollicular epidermis (IFE). The cells of the IFE are arranged in columnar struc-tural-proliferative units consisting of a single layer of basal cells at the bottom of each column (the stratum basale), two...

Fetal Wounds Have a Minimal Inflammatory Response

A major difference between fetal and adult wounds is that fetal wounds exhibit a minimal inflammatory response (McCallion and Ferguson, 1996 Yang et al., 2003 Ferguson and O'Kane, 2004), suggesting that as it matures during development, the immune system response to injury suppresses regeneration in favor of scar tissue formation. Platelets are few in number in the fetal wound. Only small numbers of platelets, neutrophils, and macrophages are present up to 18 hr after wounding (Cowin et al.,...

Brief History Of Regenerative Biology And Medicine

Our current knowledge of repair by fibrosis and regeneration has a long and fascinating history. Imprints of hands with missing fingers on the walls of Paleolithic caves have been interpreted as examples of amputations (Goss, 1991). Severe injuries such as penetrating wounds, multiple fractures, spinal cord compression, or damage to the eyes must have occurred frequently in prehistoric times, often with high morbidity and mortality. Methods to facilitate wound healing and surgical intervention...

References

Adams C, Watt FM (1990) Changes in keratinocyte adhesion during terminal differentiation reduction in fibronectin binding precedes alpha5beta1 integrin loss from the cell surface. Cell 63 425-435. Akiyama M, Dale BA, Sun TT, Holbrook K A (1995) Characterization of hair follicle bulge in human fetal skin The human fetal bulge is a pool of undifferentiated keratinocytes. J Invest Dermatol 105 844-850. Argyris TS (1976) Kinetics of epidermal production during epidermal regeneration following...

Structure Of Adult Mammalian Skin

Mammalian Skin Diagram

The skin is composed of two layers, the epidermis and dermis (figure 2.1). The epidermis is a stratified squamous epithelium consisting primarily of keratinocytes in various stages of differentiation, from mitotically active basal cells (stratum basale or stratum germinatiuum) to the heavily keratinized superficial cells (stratum corneum) that are continually sloughed. Keratinocytes are held together laterally by adhesion belts, desmo-somes, and tight junctions to form a water-impermeable...

Regeneration Of Dental Tissues

The adult human dentition consists of 32 teeth and associated periodontium, 16 in the upper and 16 in the lower jaw. figure 3.10 illustrates a section of an adult cat incisor. The bulk of the tooth consists of a central, highly vascularized and innervated pulp of mesenchymal cells surrounded by dentin, a thick, calcified collagenous matrix secreted by odontoblasts, highly differentiated postmitotic mesenchymal cells just under the dentin. Two-thirds of the dentin is embedded in a socket of...

Cell Dedifferentiation and Proliferation

Band Bungner

The distal part of an injured axon is degraded by a process called Wallerian degeneration. The mechanism of Wallerian degeneration is distinct from pathological neurodegenerative processes such as dying back from the target tissue or the pruning process observed during embryonic neurogenesis that matches the proper number of axons to their targets (Raff et al., 2002). During Wallerian degeneration, axons and their myelin layers distal to the injury disintegrate over a period of several days....

Discovery of Neural Stem Cells

Fifty years ago it was dogma that neurogenesis ceased after birth in the CNS of mammals. Then, in the early 1960s, 3H-thymidine labeling studies in adult rats revealed cells actively synthesizing DNA in the hippocampus, leading to the hypothesis that maintenance regeneration is taking place in this region of the brain (Messier et al., 1958 Smart, 1961 Altman, 1962, 1963). The idea of maintenance regeneration in the CNS of any vertebrate was not accepted, however, until Nottebohm and colleagues...

Mkl

FIGURE 6.17 Hypothesis for development of Alzheimer's disease. P and y secretases sequentially cleave the cytoplasmic domain of the amyloid precursor protein (APP) to yield P-APP and amyloidp (AP). AP leads to neurodegeneration through multiple pathways, including the formation of plaques and neurofibrillary tangles. Reproduced with permission from Cummings, Alzheimer's disease. New Eng J Med 351 56-67. Copyright 2004, Massachusetts Medical Society. FIGURE 6.17 Hypothesis for development of...

Therapies For Neurodegenerative Diseases

Demyelinating disorders, Parkinson's disease, Huntington's disease, Alzheimer's disease, and amyo-trophic lateral sclerosis (ALS) are neurodegenerative diseases that strike humans at different ages and show variable courses of progression. Huntington's disease is clearly due to a single gene mutation, as are a small percentage of ALS and Parkinson's cases. The vast majority of ALS cases, demyelinating disorders, and Parkinson's disease, however, are multifactorial in origin. Currently, about 10...

Transcription Factors Regulating Lens Regeneration

Lens Regeneration Amphibians

A number of transcription factors are required for eye development. Among the most important is Pax-6, which is considered a master gene for eye development and is also required for development of the nervous FIGURE 3.14 Regeneration of the newt lens. Pigmented cells of the dorsal iris (1) dedifferentiate to form unpigmented cells (2) that reform into a lens vesicle (3). The lens vesicle grows to fill the pupillary space as anterior epithelial cells differentiate into new lens fibers (4, 5)....

Regeneration of the Retina a Structure of the Retina

Retina Structure Rpe

Figure 5.20 illustrates the structure of the retina. The retina receives photons focused by the lens and converts them to electrical impulses that travel to the optic tectum of the brain. The retina is multilayered in all vertebrates (Ham and Cormack, 1979 Litzinger and Del-Rio Tsonis, 2002). The inner layer consists of the ganglion cells, which give rise to the optic nerve. The photoreceptor layer is composed of the light-transducing segments of the rods and cones that constitute the outer...

Potential of Nonregenerating Tissues

Regenerating Cells Muscle

First, there is substantial evidence that many mammalian tissues house ASCs that normally are not acti- TABLE 1.2 Mammalian Tissues That Do Not Regenerate in Vivo, but Harbor Stem Cells That Can Proliferate and Differentiate in Vitro TABLE 1.2 Mammalian Tissues That Do Not Regenerate in Vivo, but Harbor Stem Cells That Can Proliferate and Differentiate in Vitro * Indicates lack of regeneration after injury as opposed to maintenance regeneration. * Indicates lack of regeneration after injury as...

B Regeneration in Teleost Fish

The retina in adult teleost fish grows continually by increase in size of neurons and by addition of new neurons appositionally and interstitally (Raymond and Hitchcock, 2000 Haynes and Del-Rio Tsonis, 2004). Appositional growth occurs from a ring of neuroepithe-lial cells at the margin of the retina, called the circumferential germinal zone (CVG). Interstitial growth occurs by the addition of new rods into the layer of photoreceptors from rod precursor cells scattered throughout the outer...

Hemostasis and Clot Formation

Wounding severs blood vessels and damages epidermal and connective tissue cells and ECM. The first response to wounding is hemostasis, which occurs within a matter of minutes to stop bleeding and seal off the wound by three mechanisms formation of platelet clumps, vasoconstriction, and formation of a fibrin clot (Clark, 1996). Platelets are anucleate fragments of megakaryo- cytes, a blood cell lineage of hematopoietic stem cells in the bone marrow. Immediately upon wounding, blood suffuses the...

Reinnervation of Granulation Tissue

Medical Images Vat Scars

Peripheral sensory and sympathetic postganglionic nerves also regenerate in healing wounds and play a significant role in the formation of granulation tissue FIGURE 2.4 Comparison of collagen organization in normal uninjured dermal architecture (a) vs collagen organization in dermal scar tissue (b). The collagen of the uninjured dermis has a reticular (basket-weave) organization, whereas the collagen in a repaired dermis is cross-linked into thick bundles parallel to the wound surface....

Signals Involved in Lens Regeneration a Thrombin Activated Protein

As in other wounded tissues, serum clotting factors promote hemostasis when the pigmented epithelium is wounded by lentectomy. A major discovery was that thrombin is required to induce PECs of the newt dorsal iris cells to re-enter the cell cycle Imokawa and Brockes, 2003 . One of the first events in lens regeneration is the selective transient upregulation of active thrombin in the dorsal iris within 20-30 minutes figure 3.15 . Inactivation of thrombin by the inhibitors PPACK or antithrombin...

Amputated Amphibian and Lizard Tails

Amputation Lizards Tail

Histological and labeling studies have shown that new spinal cord neurons are produced relatively frequently in uninjured juvenile axolotls up to 6-7 months of age, but infrequently in older animals Holder et al., 1991 . Although axons of surviving neurons regenerate in larval and adult urodeles, few or no new neurons are regenerated after transection or ablation of trunk cord Butler and Ward, 1965 Nordlander and Singer, 1978 Davis et al., 1989 . By contrast, the spinal cord of larval and adult...

Bioartificial Skin Equivalents

Bioartificial skin equivalents have been developed to cover extensive excisional wounds such as burns Boyce, 2001 Yannas, 2001 Balasubramani et al., 2001 Kearney, 2001 . These constructs consist of a collagenbased or biomimetic matrix seeded with allogeneic fibroblasts and topped with a MSTSG or cultured autogeneic or allogeneic keratinocytes figure 4.3 . Because allogeneic cells are rejected and replaced by host cells, bioartificial skin equivalents do not replace host skin, but rather are...

The Mammalian

Mammalian Eye

FIGURE 3.12 Structure of the mammalian eye. The outer connective tissue capsule of the eye is the sclera, which grades into the cornea on the anterior side of the eye. The conjunctiva is a mucus membrane that covers the sclera. The iris which includes its unseen part, the ora serrata and lens form a partition between the anterior and posterior chambers of the eye. Muscles in the ciliary body control the configuration of the lens for focus. The anterior chamber is filled with an aqueous solution...