Fetal wound healing has drawn the attention of many researchers from diverse background and specialties. Fetal wound healing is unique and differs from postnatal healing in that fetal skin wounds heal rapidly without scar formation. If the mechanism underlying such phenomenon can be elucidated, it will be serve as a significant milestone in the study of wound healing. Furthermore, the implications for therapeutic applications in wound management and in diseases where scarring is the basic pathogenetic mechanism would be immense. Rather than to list the results and conflicting data of numerous studies, this article hopes to provide a general overview of the recent developments.
Animal ; Cell Adhesion Molecules/physiology ; Collagen/physiology ; Extracellular Matrix/physiology ; Fetus/*physiology ; Growth Substances/physiology ; Human ; *Wound Healing

Spermatogenesis is a complex process regulated by endocrine and testicular paracrine/autocrine factors. Gonadotropins are involved in the regulation of several testicular paracrine factors, mainly of the IL-1 family and testicular hormones. Testicular cytokines and growth factors (such as IL-1, IL-6, TNF, IFN-gamma, LIF and SCF) were shown to affect both the germ cell proliferation and the Leydig and Sertoli cells functions and secretion. Cytokines and growth factors are produced by immune cells and in the interstitial and seminiferous tubular compartments by various testicular cells, including Sertoli, Leydig, peritubular cells, spermatogonia, differentiated spermatogonia and even spermatozoa. Corresponding cytokine and growth factor receptors were demonstrated on some of the testicular cells. These cytokines also control the secretion of the gonadotropins and testosterone in the testis. Under pathological conditions the levels of pro-inflammatory cytokines are increased and negatively affected spermatogenesis. Thus, the expression levels and the mechanisms involved in the regulation of testicular paracrine/autocrine factors should be considered in future therapeutic strategies for male infertility.
Animals ; Cytokines ; physiology ; Growth Substances ; physiology ; Homeostasis ; Humans ; Leydig Cells ; cytology ; Male ; Sertoli Cells ; cytology ; Spermatogenesis ; physiology ; Testis ; physiology

With recent progress in stem cell-based research, there has been tremendous interest in stem cell-based tissue regeneration. Stem cells can be differentiated into specialized cells/tissues by growth factors and cytokines. These small molecules are thought to play an important role in both wound healing and tissue regeneration. However, their biological activity and signal transduction during tissue regeneration are poorly understood. With recent advances in signal transduction by growth factors, the receptor kinases and G protein-coupled receptors, an understanding in the underlying mechanism of how these factors regulate tissue regeneration beginning to take place. In this review, the potential underlying mechanisms of growth factor signaling in normal tissue regeneration and chronic wound healing is discussed. Thus, it is an aim to provide a basis for designing more specific therapies for tissue regeneration in the near future.
Animal ; Cell Physiology* ; Chemokines/physiology ; Chronic Disease ; Growth Substances/physiology ; Human ; Keloid/therapy ; Keloid/physiopathology ; Regeneration/physiology* ; Signal Transduction/physiology* ; Wound Healing/physiology

Tissue engineering has been applied to various tissues, and particularly significant progress has been made in the areas of skin, cartilage, and bone regeneration. Inclusion of bioactive factors into the synthetic scaffolds has been suggested as one of the possible tissue engineering strategies. The growth factors are polypeptides that transmit signals to modulate cellular activities. They have short half-lives, for example, platelet-derived growth factor (PDGF), isolated from platelets, has a half life of less than 2 minutes when injected intravenously. Extended biological activity and the controlled release of growth factor are achieved by incorporating growth factor into the polymeric device. This review will focus on growth factor delivery for tissue engineering. Particular examples will be given whereby growth factors are delivered from a tissue-engineered device to facilitate wound healing and tissue repair.
Animal ; Biomedical Engineering/methods* ; Bone Morphogenetic Proteins/administration & dosage ; Cytokines/therapeutic use ; Cytokines/administration & dosage* ; Growth Substances/physiology

Recently, thanks to the rapid progress of new technologies in cell modulation, extracellular matrix fabrication and synthetic polymers mimicking bodily structures, the self-regeneration of bodily defects by host tissue has been considered by many researchers. The conventional science of art in biomaterials has been concerned with restoring damaged tissue using non-biological materials such as metals, ceramics and synthetic polymers. To overcome the limitations of using such non-viable materials, several attempts to construct artificial organs mimicking natural tissue by combining modulated cells with extracellular matrix-hybridized synthetic polymers have produced many worthy results with biologically functioning artificial tissues. The process involved in manufacturing biomaterials mimicking living tissue is generally called tissue engineering. However recently, the extension of knowledge about cell biology and embryology has naturally moved the focus from tissue restoration to tissue regeneration. Especially, embryonic and mesenchymal stem cells are attractive resources due to their potential for the differentiation of various tissue cells in response to signal transduction mediated by cytokines. Although no one knows yet what is the exact factor responsible for a stem cell's ability to differentiate between specific cells to generate specific tissue, what has been agreed is that delivering stem cells into the body provides a strong potential for the regeneration of tissue. In this review, the historical issues and future possibilities involved in medical tissue restoration and tissue regeneration are discussed.
Animal ; Biocompatible Materials/therapeutic use ; Biodegradation ; Biomedical Engineering*y ; Cell Transplantation/methods ; Extracellular Matrix/physiology ; Growth Substances/therapeutic use ; Growth Substances/administration & dosage ; Human ; Polymers/therapeutic use ; Regeneration* ; Stem Cells/transplantation

Glypican-3 (GPC3) encodes a cell-surface heparan-sulfate proteoglycan and its expression is frequently silenced in ovarian cancer, mesotheliomas, and breast cancer cell lines and ectopic expression of GPC3 inhibited the growth of these cells, suggesting that GPC3 plays a negative role in cell proliferation. In contrast, up-regulation of GPC3 is often observed in hepatoma, neuroblastoma, and Wilms' tumor. Whether GPC3 plays the same growth inhibitory role in these tumors remains to be studied. Here we report that antisense-mediated knockdown of GPC3 in the HepG2 hepatoma cells significantly promotes the growth of hepatoma cells. In addition, we show that this growth promotion is independent of insulin-like growth factor 2 (IGF2) signaling. Our data suggest that GPC3 plays a growth-suppressing role in hepatoma and provide cell biological evidence inconsistent with the hypothesis that GPC3 acts as a growth suppressor by downregulating IGF2.
Carcinoma, Hepatocellular/*metabolism ; Growth Substances/*metabolism ; Heparan Sulfate Proteoglycan/*metabolism ; Human ; Insulin-Like Growth Factor II/*metabolism ; RNA, Antisense ; Signal Transduction/physiology

The epididymis is divided into caput, corpus and cauda regions, organized into intraregional segments separated by connective tissue septa (CTS). In the adult rat and mouse these segments are highly differentiated. Regulation of these segments is by endocrine, lumicrine and paracrine factors, the relative importance of which remains under investigation. Here, the ability of the CTS to limit signaling in the interstitial compartment is reviewed as is the effect of 15 days of unilateral efferent duct ligation (EDL) on ipsilateral segmental transcriptional profiles. Inter-segmental microperifusions of epidermal growth factor (EGF), vascular endothelial growth factor (VEGFA) and fibroblast growth factor 2 (FGF2) increased phosphorylation of mitogen activated protein kinase (MAPK) in segments 1 and 2 of the rat epididymis and the effects of all factors were limited by the CTS separating the segments. Microarray analysis of segmental gene expression determined the effect of 15 days of unilateral EDL on the transcriptome-wide gene expression of rat segments 1-4. Over 11,000 genes were expressed in each of the four segments and over 2000 transcripts in segment 1 responded to deprivation of testicular lumicrine factors. Segments 1 and 2 of control tissues were the most transcriptionally different and EDL had its greatest effects there. In the absence of lumicrine factors, all four segments regressed to a transcriptionally undifferentiated state, consistent with the less differentiated histology. Deprivation of lumicrine factors could stimulate an individual gene's expression in some segments yet suppress it in others. Such results reveal a higher complexity of the regulation of rat epididymal segments than that is generally appreciated.
Animals ; Ejaculatory Ducts ; physiology ; Epididymis ; drug effects ; physiology ; Gene Expression Regulation ; drug effects ; Growth Substances ; pharmacology ; Male ; Mice ; Rats ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction

The regulation roles of insulin-like growth factor-1 (IGF-1) with basic fibroblast growth factor (bFGF) and transforming growth factor beta 2 (TGFbeta2) in human nasal septum chondrocytes monolayer culture and cartilage engineering was investigated in this study. The role of IGF-1 with bFGF and TGFbeta2 was investigated by measuring chondrocyte growth kinetic and collagen genes expression. IGF-1 together with bFGF and TGFbeta2 promote cartilage tissue engineering, increase type II collagen expression and enhance the histological features of engineered cartilage.
Cartilage/*transplantation ; Cell Division/physiology ; Chondrocytes/*cytology ; Collagen Type II/genetics ; Culture Media, Serum-Free ; Gene Expression/physiology ; Growth Substances/*physiology ; Insulin-Like Growth Factor I/*physiology ; Tissue Engineering/*methods

Child ; Child Development ; drug effects ; Endocrine Glands ; drug effects ; growth & development ; physiology ; Hazardous Substances ; poisoning ; Humans ; Nervous System ; drug effects ; Urogenital System ; drug effects

Mouse spleen cells activated in a mixed lymphocyte reaction release a soluble factor, which induces a significant proliferative response in fresh mouse spleen cells. This proliferation inducing factor (PIF) was found to be heat stable (90 degrees C for 45 min) and also resistant to trypsin or chymotrypsin treatment. By using a sizing HPLC column, the molecular weight of PIF appears to be 25 kDa. Mouse spleen cells treated with anti-thy-1 + complement lost Con-A induced proliferative responses but responded well to PIF. B cell depleted spleen cells obtained by negative selection panning, did not respond to PIF. These results indicate that B cells proliferated in response to PIF. Polymixin-B, which blocks the B cell proliferative response to LPS, did not inhibit PIF induced proliferation.
Animal ; B-Lymphocytes/physiology* ; B-Lymphocytes/drug effects ; Bone Marrow/metabolism ; Cell Division/physiology ; Chromatography, High Pressure Liquid ; Chymotrypsin/pharmacology ; Dose-Response Relationship, Drug ; Growth Substances/pharmacology* ; Growth Substances/chemistry ; Heat ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Molecular Weight ; Polymyxin B/pharmacology ; Protein Denaturation ; Spleen/metabolism* ; Thymus Gland/metabolism ; Trypsin/pharmacology