Anna Gosiewska - Academia.edu (original) (raw)

Papers by Anna Gosiewska

Purification and properties of N-acetyl-beta-D-glucosaminidase from human gastric mucous membrane

PubMed, 1986

Tissue Engineering Part C-methods, Jul 1, 2014

Human in vitro-manufactured tissue and organ models can serve as powerful enabling tools for the ... more Human in vitro-manufactured tissue and organ models can serve as powerful enabling tools for the exploration of fundamental questions regarding cell, matrix, and developmental biology in addition to the study of drug delivery dynamics and kinetics. To date, the development of a human model of the renal proximal tubule (PT) has been hindered by the lack of an appropriate cell source and scaffolds that allow epithelial monolayer formation and maintenance. Using extracellular matrices or matrix proteins, an in vivo-mimicking environment can be created that allows epithelial cells to exhibit their typical phenotype and functionality. Here, we describe an in vitro-engineered PT model. We isolated highly proliferative cells from cadaveric human kidneys (human kidney-derived cells [hKDCs]), which express markers that are associated with renal progenitor cells. Seeded on small intestinal submucosa (SIS), hKDCs formed a confluent monolayer and displayed the typical phenotype of PT epithelial cells. PT markers, including N-cadherin, were detected throughout the hKDC culture on the SIS, whereas markers of later tubule segments were weak (E-cadherin) or not (aquaporin-2) expressed. Basement membrane and microvilli formation demonstrated a strong polarization. We conclude that the combination of hKDCs and SIS is a suitable cell-scaffold composite to mimic the human PT in vitro.

Cell Transplantation, Sep 1, 2013

Intravenous administration of human umbilical tissue-derived cells (hUTC) improves neurological f... more Intravenous administration of human umbilical tissue-derived cells (hUTC) improves neurological function in young adult rats after stroke. However, stroke is a major cause of death and disability in the aged population, with the majority of stroke patients 65 years and older. The present study investigated the effect of hUTC on aged rats after embolic stroke. Rats at the age of 18-20 months were subjected to embolic middle cerebral artery (MCA) occlusion. Two groups of eight animals each were compared. The investigational group was injected intravenously with 1 × 10 7 cells/kg in serum-free culture medium (vehicle) 24 h after stroke onset, and the control group was treated with vehicle only at the same time poststroke. Intravenous administration of hUTC significantly improved neurological functional recovery without reducing infarct volume compared to vehicle-treated aged rats. Additionally, hUTC treatment significantly enhanced synaptogenesis and vessel density in the ischemic boundary zone (IBZ). Moreover, hUTC treatment resulted in a trend toward increased progenitor cell proliferation in the subventricular zone (SVZ) compared to vehicle-treated aged rats. Intravenous administration of hUTC improved functional recovery in aged rats after stroke. The enhancement of synaptogenesis and vessel density may contribute to the beneficial effects of hUTC in the treatment of stroke in the aged animal.

Journal of Materials Science: Materials in Medicine

Differences in scaffold design have the potential to influence cell-scaffold interactions. This s... more Differences in scaffold design have the potential to influence cell-scaffold interactions. This study sought to determine whether a tri-layer design influences the cellular function of human tenocytes in vitro. The single-layer decellularized, dehydrated human amniotic membrane (DDHAM) and the tri-layer DDHAM (DDHAM-3L) similarly supported tenocyte function as evidenced by improved cell growth and migration, reduced dedifferentiation, and an attenuated inflammatory response. The tri-layer design provides a mechanically more robust scaffold without altering biological activity. Graphical Abstract

An in vitro comparison of human corneal epithelial cell activity and inflammatory response on differently designed ocular amniotic membranes and a clinical case study

Journal of Biomedical Materials Research Part B: Applied Biomaterials

Amniotic membrane (AM) is a naturally derived biomaterial with biological and mechanical properti... more Amniotic membrane (AM) is a naturally derived biomaterial with biological and mechanical properties important to Ophthalmology. The epithelial side of the AM promotes epithelialization, while the stromal side regulates inflammation. However, not all AMs are equal. AMs undergo different processing with resultant changes in cellular content and structure. This study evaluates the effects of sidedness and processing on human corneal epithelial cell (HCEC) activity, the effect of processing on HCEC inflammatory response, and then a case study is presented. Three differently processed, commercially available ocular AMs were selected: (1) Biovance®3L Ocular, a decellularized, dehydrated human AM (DDHAM), (2) AMBIO2®, a dehydrated human AM (DHAM), and (3) AmnioGraft®, a cryopreserved human AM (CHAM). HCECs were seeded onto the AMs and incubated for 1, 4 and 7 days. Cell adhesion and viability were evaluated using alamarBlue assay. HCEC migration was evaluated using a scratch wound assay. A...

Flowable placental connective tissue matrices for tendon repair: A review

Journal of Biology and Medicine

Tendon injuries are associated with considerable pain and disability. Owing to the hypovascularit... more Tendon injuries are associated with considerable pain and disability. Owing to the hypovascularity and hypocellularity of the tissue, natural tendon healing is slow and ineffective. Traditional conservative and surgical treatment options fail to address the underlying pathology. As a result, the healed tendon is mechanically incompetent and prone to degeneration and rupture. Therefore, new biological methods have been suggested to enhance tendon repair and regeneration. Flowable Placental Connective Tissue Matrices (FP-CTMs) represent a promising means to promote tendon healing. Like non-flowable placental scaffolds, FP-CTMs possess the innate healing properties of the placenta and provide structural and biochemical extracellular matrix components. Unlike their non-flowable counterparts, FP-CTMs have the added benefits of minimal invasiveness and the capacity to fill irregular spaces. FP-CTMs can enhance tendon repair by providing a three-dimensional extracellular matrix for cellula...

Intravenous administration of human umbilical cord blood-mononuclear cells dose-dependently relieve neurologic deficits in rat intracerebral hemorrhage model

Annals of Anatomy - Anatomischer Anzeiger, 2013

Human umbilical cord blood (HUCB) is now considered as a valuable source for stem cell-based ther... more Human umbilical cord blood (HUCB) is now considered as a valuable source for stem cell-based therapies. Previous studies showed that intravascular injection of the HUCB significantly improves neurological functional recovery in a model of intracerebral hemorrhage (ICH). To extend these findings, we examined the behavioral recovery and injured volume in the presence of increasing doses of human umbilical cord blood derived mononuclear cells (HUC-MCs) after intracerebral hemorrhage in rats. The experimental ICH was induced by intrastriatal administration of bacterial collagenase IV in adult rats. One day after the surgery, the rats were randomly divided into 4 groups to receive intravenously either BrdU positive human UC-MCs (4 × 10(6), 8 × 10(6) and 16 × 10(6) cells in 1 ml saline, n=10, respectively) as treated groups or the same amount of saline as lesion group (n=10). There was also one group (control n=10) that received only the vehicle solution of collagenase. The animals were evaluated for 14 days with modified limb placing and corner turn tests. The transplanted human UC-MCs were also detected by immunohistochemistry with labeling of BrdU. Two weeks after infusion, there was a significant recovery in the behavioral performance when 4 × 10(6) or more UC-MCs were delivered (P<0.05-0.001). Injured volume measurements disclosed an inverse relationship between UC-MCs dose and damage reaching significance at the higher UC-MCs doses. Moreover, human UC-MCs were localized by immunohistochemistry only in the injured area. Intravenously transplanted UC-MCs can accelerate the neurological function recovery of ICH rat and diminish the striatum lesion size by demonstrating a dose relationship between them.

Growth Factors Journal, 1994

Insulin-like growth factor binding proteins (IGFBPs) play crucial roles in regulating the availab... more Insulin-like growth factor binding proteins (IGFBPs) play crucial roles in regulating the availability of IGFs to receptors and prolong the half-lives of IGFs. There are six IGFBPs present in the mammalian circulation with IGFBP-3 being most abundant. In mammals IGFBP-3 is the major carrier of circulating IGFs, facilitated by forming a ternary complex with IGF and an acid-labile subunit (ALS). IGFBP-1 is generally inhibitory to IGF action by preventing it from interacting with its receptors. In teleosts, the third-round of vertebrate whole genome duplication created paralogs of each IGFBP, except IGFBP-4. In the fish circulation, three major IGFBPs are typically detected at molecular ranges of 20-25, 28-32 and 40-50 kDa. However, their identities are not well established. Three major circulating IGFBPs in Chinook salmon have been identified through protein purification and cDNA cloning. Salmon 28-and 22-kDa IGFBPs are co-orthologs of IGFBP-1, termed IGFBP-1a and-1b, respectively. They are induced under catabolic conditions such as stress and fasting but their responses are somewhat different, with IGFBP-1b being the most sensitive of the two. Cortisol stimulates production and secretion of these IGFBP-1 subtypes while, unlike in mammals, insulin may not be a primary suppressor. Salmon 41-kDa IGFBP, a major carrier of IGF-I, is not IGFBP-3, as might be expected extrapolating from mammals, but is in fact IGFBP-2b. Salmon IGFBP-2b levels in plasma are high when fish are fed, and GH treatment increases its circulating levels similar to mammalian IGFBP-3. These findings suggest that salmon IGFBP-2b acquired the role and regulation similar to mammalian IGFBP-3. Multiple replication of fish IGFBPs offer a unique opportunity to investigate molecular evolution of IGFBPs.

Species differences in cis‐elements of the Proα1(I) procollagen promoter and their binding proteins

Journal of Cellular Biochemistry, Jun 1, 1999

Abstract Previous studies suggest that there may be species differences in the utilization of cis... more Abstract Previous studies suggest that there may be species differences in the utilization of cis-elements of the type I collagen genes. The present study was designed to examine this possibility by focusing on two regions of the proα1 (I) collagen promoter. One is the GC-...

Insulin-like growth factor (IGF) binding proteins and their mRNAs in connective tissues of fasted guinea-pigs

Endocrine journal, Dec 1, 1995

Fasting (with vitamin C-supplementation) and vitamin C-deficiency in guinea-pigs are associated w... more Fasting (with vitamin C-supplementation) and vitamin C-deficiency in guinea-pigs are associated with decreased collagen gene expression in connective tissues. Recently we presented evidence that circulating insulin-like growth factor binding protein (IGFBP)-1 and-2 that are induced during both nutritional deficiencies may be responsible for this inhibition by interfering with IGF-I action. The present objective was to determine whether circulating IGFBPs are accumulated in bone, skin and cartilage during fasting, which would support an endocrine role for them. IGFBP-1 mRNA was not detected in any of the connective tissues. The protein, as measured by ligand blotting, was not present in tissues of normal animals but accumulated early during fasting in all of the tissues. Bone and cartilage from normal animals contained IGFBP-2 and its mRNA, but only in bone did their levels increase during fasting. IGFBP-3 mRNA was not detected in connective tissues from normal or fasted guinea-pigs. Little or no IGFBP-3 was detected in normal tissue extracts, but protein accumulated during fasting and presumably was derived from the circulation. IGF-I and-II mRNAs were expressed in bone and cartilage but in skin, only IGF-II mRNA was detected. Affinity cross-linking revealed that in skin, IGFBP-3 contained relatively few unoccupied IGF-I binding sites compared to IGFBP-1 while in bone and cartilage, only IGFBP-1 contained unoccupied binding sites. IGFBP-1, acting by endocrine action, is probably the major factor responsible for inhibition of IGF-I-dependent collagen gene expression during fasting.

Characterization of the platelet-derived growth factor β-receptor kinase activity by use of synthetic peptides

Biochemical and Biophysical Research Communications, 1990

Synthetic peptides derived from the sequence surrounding tyrosine-857 in the human platelet-deriv... more Synthetic peptides derived from the sequence surrounding tyrosine-857 in the human platelet-derived growth factor (PDGF) beta-receptor were used to elucidate the requirement for length and presence of negative and positively charged amino acids in substrates of the PDGF beta-receptor protein tyrosine kinase. The measured Km for the different peptides were all in the range 1-10 mM. A peptide of only five amino acids, lacking acidic amino acid residues, were found to be substrates for the receptor kinase. Ligand binding was found to stimulate the phosphorylation of peptides mainly by lowering the Km both for peptide and for ATP. Only minor changes in the Vmax occurred upon stimulation with PDGF. The reaction mechanism was found to be sequential, i.e. both the peptide and ATP have to bind to the enzyme before any product is released.

Chronic wounds are associated with considerable patient morbidity and present a significant econo... more Chronic wounds are associated with considerable patient morbidity and present a significant economic burden to the healthcare system. Often, chronic wounds are in a state of persistent in-flammation and unable to progress to the next phase of wound healing. Placental-derived bio-materials are recognized for their biocompatibility, biodegradability, angiogenic, an-ti-inflammatory, anti-microbial, anti-fibrotic, immunomodulatory, and immune privileged prop-erties. As such, placental-derived biomaterials have been used in wound management for more than a century. Placental-derived scaffolds are composed of an extracellular matrix (ECM) that can mimic the native tissue, creating a reparative environment to promote ECM remodeling, cell migration, proliferation, and differentiation. Reliable evidence exists throughout the literature to support the safety and effectiveness of placental-derived biomaterials in wound healing. How-ever, differences in source (i.e., anatomical regions of the p...

Insulin-like growth factor (IGF) binding proteins and their mRNAs in connective tissues of fasted guinea-pigs

Fasting (with vitamin C-supplementation) and vitamin C-deficiency in guinea-pigs are associated w... more Fasting (with vitamin C-supplementation) and vitamin C-deficiency in guinea-pigs are associated with decreased collagen gene expression in connective tissues. Recently we presented evidence that circulating insulin-like growth factor binding protein (IGFBP)-1 and-2 that are induced during both nutritional deficiencies may be responsible for this inhibition by interfering with IGF-I action. The present objective was to determine whether circulating IGFBPs are accumulated in bone, skin and cartilage during fasting, which would support an endocrine role for them. IGFBP-1 mRNA was not detected in any of the connective tissues. The protein, as measured by ligand blotting, was not present in tissues of normal animals but accumulated early during fasting in all of the tissues. Bone and cartilage from normal animals contained IGFBP-2 and its mRNA, but only in bone did their levels increase during fasting. IGFBP-3 mRNA was not detected in connective tissues from normal or fasted guinea-pigs. Little or no IGFBP-3 was detected in normal tissue extracts, but protein accumulated during fasting and presumably was derived from the circulation. IGF-I and-II mRNAs were expressed in bone and cartilage but in skin, only IGF-II mRNA was detected. Affinity cross-linking revealed that in skin, IGFBP-3 contained relatively few unoccupied IGF-I binding sites compared to IGFBP-1 while in bone and cartilage, only IGFBP-1 contained unoccupied binding sites. IGFBP-1, acting by endocrine action, is probably the major factor responsible for inhibition of IGF-I-dependent collagen gene expression during fasting.

Populations de cellules extraites de reins et leur utilisation pour la réparation et le régénération de tissus

L'invention porte sur des populations de cellules extraites de tissus de reins de mammiferes ... more L'invention porte sur des populations de cellules extraites de tissus de reins de mammiferes isolees ou purifiees, sur des methodes d'isolement et de purification de ces populations de cellules, et sur des methodes de traitement de maladies renales par administration de ces populations de cellules a des mammiferes.

Zusammensetzung mit glycosaminogycanen und hyaluronidase-hemmern zur behandlung arthritischer gelenke

Nouveau peptide a activite osteogene

La presente invention concerne une composition comprenant un composant de peptide isole ou recomb... more La presente invention concerne une composition comprenant un composant de peptide isole ou recombinant qui a une activite de proliferation de cellules osteogenes. Le peptide, qui favorise la proliferation d'osteoblastes, est utile dans le traitement des fractures, en tant qu'element de remplissage de sites osseux deficients, pour inhiber le decroissement de la substance osseuse du a l'osteoporose et aux maladies parodontales, et dans la prevention des fractures associees a l'osteoporose ou a l'arthrite rhumatoide. Le peptide de l'invention, ou les cellules modifiees genetiquement pour produire le peptide, peut etre combine avec une matrice compatible avec les os afin de faciliter la liberation lente du peptide dans un site de traitement et/ou pour creer une structure de developpement de l'os.

Regeneration und reparatur von nervengewebe nach einer verletzung

Cellules dérivées de cordon ombilical post-partum pour l'utilisation dans le traitement de maladies du coeur et du système circulatoire

Regeneration and Repair of Neural Tissue Using

Journal of Experimental Orthopaedics

Purpose Injectable connective tissue matrices (CTMs) may promote tendon healing, given their mini... more Purpose Injectable connective tissue matrices (CTMs) may promote tendon healing, given their minimally invasive properties, structural and biochemical extracellular matrix components, and capacity to fill irregular spaces. The purpose of this study is to evaluate the effects of placental CTMs on the cellular activities of human tenocytes. Decellularization, the removal of cells, cell fragments, and DNA from CTMs, has been shown to reduce the host’s inflammatory response. Therefore, the authors hypothesize that a decellularized CTM will provide a more cell-friendly matrix to support tenocyte functions. Methods Three human placental CTMs were selected for comparison: AmnioFill® (A-CTM), a minimally manipulated, non-viable cellular particulate, BioRenew™ (B-CTM), a liquid matrix, and Interfyl® (I-CTM), a decellularized flowable particulate. Adhesion and proliferation were evaluated using cell viability assays and tenocyte migration using a transwell migration assay. Gene expression of ...

Purification and properties of N-acetyl-beta-D-glucosaminidase from human gastric mucous membrane

PubMed, 1986

Tissue Engineering Part C-methods, Jul 1, 2014

Human in vitro-manufactured tissue and organ models can serve as powerful enabling tools for the ... more Human in vitro-manufactured tissue and organ models can serve as powerful enabling tools for the exploration of fundamental questions regarding cell, matrix, and developmental biology in addition to the study of drug delivery dynamics and kinetics. To date, the development of a human model of the renal proximal tubule (PT) has been hindered by the lack of an appropriate cell source and scaffolds that allow epithelial monolayer formation and maintenance. Using extracellular matrices or matrix proteins, an in vivo-mimicking environment can be created that allows epithelial cells to exhibit their typical phenotype and functionality. Here, we describe an in vitro-engineered PT model. We isolated highly proliferative cells from cadaveric human kidneys (human kidney-derived cells [hKDCs]), which express markers that are associated with renal progenitor cells. Seeded on small intestinal submucosa (SIS), hKDCs formed a confluent monolayer and displayed the typical phenotype of PT epithelial cells. PT markers, including N-cadherin, were detected throughout the hKDC culture on the SIS, whereas markers of later tubule segments were weak (E-cadherin) or not (aquaporin-2) expressed. Basement membrane and microvilli formation demonstrated a strong polarization. We conclude that the combination of hKDCs and SIS is a suitable cell-scaffold composite to mimic the human PT in vitro.

Cell Transplantation, Sep 1, 2013

Intravenous administration of human umbilical tissue-derived cells (hUTC) improves neurological f... more Intravenous administration of human umbilical tissue-derived cells (hUTC) improves neurological function in young adult rats after stroke. However, stroke is a major cause of death and disability in the aged population, with the majority of stroke patients 65 years and older. The present study investigated the effect of hUTC on aged rats after embolic stroke. Rats at the age of 18-20 months were subjected to embolic middle cerebral artery (MCA) occlusion. Two groups of eight animals each were compared. The investigational group was injected intravenously with 1 × 10 7 cells/kg in serum-free culture medium (vehicle) 24 h after stroke onset, and the control group was treated with vehicle only at the same time poststroke. Intravenous administration of hUTC significantly improved neurological functional recovery without reducing infarct volume compared to vehicle-treated aged rats. Additionally, hUTC treatment significantly enhanced synaptogenesis and vessel density in the ischemic boundary zone (IBZ). Moreover, hUTC treatment resulted in a trend toward increased progenitor cell proliferation in the subventricular zone (SVZ) compared to vehicle-treated aged rats. Intravenous administration of hUTC improved functional recovery in aged rats after stroke. The enhancement of synaptogenesis and vessel density may contribute to the beneficial effects of hUTC in the treatment of stroke in the aged animal.

Journal of Materials Science: Materials in Medicine

Differences in scaffold design have the potential to influence cell-scaffold interactions. This s... more Differences in scaffold design have the potential to influence cell-scaffold interactions. This study sought to determine whether a tri-layer design influences the cellular function of human tenocytes in vitro. The single-layer decellularized, dehydrated human amniotic membrane (DDHAM) and the tri-layer DDHAM (DDHAM-3L) similarly supported tenocyte function as evidenced by improved cell growth and migration, reduced dedifferentiation, and an attenuated inflammatory response. The tri-layer design provides a mechanically more robust scaffold without altering biological activity. Graphical Abstract

An in vitro comparison of human corneal epithelial cell activity and inflammatory response on differently designed ocular amniotic membranes and a clinical case study

Journal of Biomedical Materials Research Part B: Applied Biomaterials

Amniotic membrane (AM) is a naturally derived biomaterial with biological and mechanical properti... more Amniotic membrane (AM) is a naturally derived biomaterial with biological and mechanical properties important to Ophthalmology. The epithelial side of the AM promotes epithelialization, while the stromal side regulates inflammation. However, not all AMs are equal. AMs undergo different processing with resultant changes in cellular content and structure. This study evaluates the effects of sidedness and processing on human corneal epithelial cell (HCEC) activity, the effect of processing on HCEC inflammatory response, and then a case study is presented. Three differently processed, commercially available ocular AMs were selected: (1) Biovance®3L Ocular, a decellularized, dehydrated human AM (DDHAM), (2) AMBIO2®, a dehydrated human AM (DHAM), and (3) AmnioGraft®, a cryopreserved human AM (CHAM). HCECs were seeded onto the AMs and incubated for 1, 4 and 7 days. Cell adhesion and viability were evaluated using alamarBlue assay. HCEC migration was evaluated using a scratch wound assay. A...

Flowable placental connective tissue matrices for tendon repair: A review

Journal of Biology and Medicine

Tendon injuries are associated with considerable pain and disability. Owing to the hypovascularit... more Tendon injuries are associated with considerable pain and disability. Owing to the hypovascularity and hypocellularity of the tissue, natural tendon healing is slow and ineffective. Traditional conservative and surgical treatment options fail to address the underlying pathology. As a result, the healed tendon is mechanically incompetent and prone to degeneration and rupture. Therefore, new biological methods have been suggested to enhance tendon repair and regeneration. Flowable Placental Connective Tissue Matrices (FP-CTMs) represent a promising means to promote tendon healing. Like non-flowable placental scaffolds, FP-CTMs possess the innate healing properties of the placenta and provide structural and biochemical extracellular matrix components. Unlike their non-flowable counterparts, FP-CTMs have the added benefits of minimal invasiveness and the capacity to fill irregular spaces. FP-CTMs can enhance tendon repair by providing a three-dimensional extracellular matrix for cellula...

Intravenous administration of human umbilical cord blood-mononuclear cells dose-dependently relieve neurologic deficits in rat intracerebral hemorrhage model

Annals of Anatomy - Anatomischer Anzeiger, 2013

Human umbilical cord blood (HUCB) is now considered as a valuable source for stem cell-based ther... more Human umbilical cord blood (HUCB) is now considered as a valuable source for stem cell-based therapies. Previous studies showed that intravascular injection of the HUCB significantly improves neurological functional recovery in a model of intracerebral hemorrhage (ICH). To extend these findings, we examined the behavioral recovery and injured volume in the presence of increasing doses of human umbilical cord blood derived mononuclear cells (HUC-MCs) after intracerebral hemorrhage in rats. The experimental ICH was induced by intrastriatal administration of bacterial collagenase IV in adult rats. One day after the surgery, the rats were randomly divided into 4 groups to receive intravenously either BrdU positive human UC-MCs (4 × 10(6), 8 × 10(6) and 16 × 10(6) cells in 1 ml saline, n=10, respectively) as treated groups or the same amount of saline as lesion group (n=10). There was also one group (control n=10) that received only the vehicle solution of collagenase. The animals were evaluated for 14 days with modified limb placing and corner turn tests. The transplanted human UC-MCs were also detected by immunohistochemistry with labeling of BrdU. Two weeks after infusion, there was a significant recovery in the behavioral performance when 4 × 10(6) or more UC-MCs were delivered (P<0.05-0.001). Injured volume measurements disclosed an inverse relationship between UC-MCs dose and damage reaching significance at the higher UC-MCs doses. Moreover, human UC-MCs were localized by immunohistochemistry only in the injured area. Intravenously transplanted UC-MCs can accelerate the neurological function recovery of ICH rat and diminish the striatum lesion size by demonstrating a dose relationship between them.

Growth Factors Journal, 1994

Insulin-like growth factor binding proteins (IGFBPs) play crucial roles in regulating the availab... more Insulin-like growth factor binding proteins (IGFBPs) play crucial roles in regulating the availability of IGFs to receptors and prolong the half-lives of IGFs. There are six IGFBPs present in the mammalian circulation with IGFBP-3 being most abundant. In mammals IGFBP-3 is the major carrier of circulating IGFs, facilitated by forming a ternary complex with IGF and an acid-labile subunit (ALS). IGFBP-1 is generally inhibitory to IGF action by preventing it from interacting with its receptors. In teleosts, the third-round of vertebrate whole genome duplication created paralogs of each IGFBP, except IGFBP-4. In the fish circulation, three major IGFBPs are typically detected at molecular ranges of 20-25, 28-32 and 40-50 kDa. However, their identities are not well established. Three major circulating IGFBPs in Chinook salmon have been identified through protein purification and cDNA cloning. Salmon 28-and 22-kDa IGFBPs are co-orthologs of IGFBP-1, termed IGFBP-1a and-1b, respectively. They are induced under catabolic conditions such as stress and fasting but their responses are somewhat different, with IGFBP-1b being the most sensitive of the two. Cortisol stimulates production and secretion of these IGFBP-1 subtypes while, unlike in mammals, insulin may not be a primary suppressor. Salmon 41-kDa IGFBP, a major carrier of IGF-I, is not IGFBP-3, as might be expected extrapolating from mammals, but is in fact IGFBP-2b. Salmon IGFBP-2b levels in plasma are high when fish are fed, and GH treatment increases its circulating levels similar to mammalian IGFBP-3. These findings suggest that salmon IGFBP-2b acquired the role and regulation similar to mammalian IGFBP-3. Multiple replication of fish IGFBPs offer a unique opportunity to investigate molecular evolution of IGFBPs.

Species differences in cis‐elements of the Proα1(I) procollagen promoter and their binding proteins

Journal of Cellular Biochemistry, Jun 1, 1999

Abstract Previous studies suggest that there may be species differences in the utilization of cis... more Abstract Previous studies suggest that there may be species differences in the utilization of cis-elements of the type I collagen genes. The present study was designed to examine this possibility by focusing on two regions of the proα1 (I) collagen promoter. One is the GC-...

Insulin-like growth factor (IGF) binding proteins and their mRNAs in connective tissues of fasted guinea-pigs

Endocrine journal, Dec 1, 1995

Fasting (with vitamin C-supplementation) and vitamin C-deficiency in guinea-pigs are associated w... more Fasting (with vitamin C-supplementation) and vitamin C-deficiency in guinea-pigs are associated with decreased collagen gene expression in connective tissues. Recently we presented evidence that circulating insulin-like growth factor binding protein (IGFBP)-1 and-2 that are induced during both nutritional deficiencies may be responsible for this inhibition by interfering with IGF-I action. The present objective was to determine whether circulating IGFBPs are accumulated in bone, skin and cartilage during fasting, which would support an endocrine role for them. IGFBP-1 mRNA was not detected in any of the connective tissues. The protein, as measured by ligand blotting, was not present in tissues of normal animals but accumulated early during fasting in all of the tissues. Bone and cartilage from normal animals contained IGFBP-2 and its mRNA, but only in bone did their levels increase during fasting. IGFBP-3 mRNA was not detected in connective tissues from normal or fasted guinea-pigs. Little or no IGFBP-3 was detected in normal tissue extracts, but protein accumulated during fasting and presumably was derived from the circulation. IGF-I and-II mRNAs were expressed in bone and cartilage but in skin, only IGF-II mRNA was detected. Affinity cross-linking revealed that in skin, IGFBP-3 contained relatively few unoccupied IGF-I binding sites compared to IGFBP-1 while in bone and cartilage, only IGFBP-1 contained unoccupied binding sites. IGFBP-1, acting by endocrine action, is probably the major factor responsible for inhibition of IGF-I-dependent collagen gene expression during fasting.

Characterization of the platelet-derived growth factor β-receptor kinase activity by use of synthetic peptides

Biochemical and Biophysical Research Communications, 1990

Synthetic peptides derived from the sequence surrounding tyrosine-857 in the human platelet-deriv... more Synthetic peptides derived from the sequence surrounding tyrosine-857 in the human platelet-derived growth factor (PDGF) beta-receptor were used to elucidate the requirement for length and presence of negative and positively charged amino acids in substrates of the PDGF beta-receptor protein tyrosine kinase. The measured Km for the different peptides were all in the range 1-10 mM. A peptide of only five amino acids, lacking acidic amino acid residues, were found to be substrates for the receptor kinase. Ligand binding was found to stimulate the phosphorylation of peptides mainly by lowering the Km both for peptide and for ATP. Only minor changes in the Vmax occurred upon stimulation with PDGF. The reaction mechanism was found to be sequential, i.e. both the peptide and ATP have to bind to the enzyme before any product is released.

Chronic wounds are associated with considerable patient morbidity and present a significant econo... more Chronic wounds are associated with considerable patient morbidity and present a significant economic burden to the healthcare system. Often, chronic wounds are in a state of persistent in-flammation and unable to progress to the next phase of wound healing. Placental-derived bio-materials are recognized for their biocompatibility, biodegradability, angiogenic, an-ti-inflammatory, anti-microbial, anti-fibrotic, immunomodulatory, and immune privileged prop-erties. As such, placental-derived biomaterials have been used in wound management for more than a century. Placental-derived scaffolds are composed of an extracellular matrix (ECM) that can mimic the native tissue, creating a reparative environment to promote ECM remodeling, cell migration, proliferation, and differentiation. Reliable evidence exists throughout the literature to support the safety and effectiveness of placental-derived biomaterials in wound healing. How-ever, differences in source (i.e., anatomical regions of the p...

Insulin-like growth factor (IGF) binding proteins and their mRNAs in connective tissues of fasted guinea-pigs

Fasting (with vitamin C-supplementation) and vitamin C-deficiency in guinea-pigs are associated w... more Fasting (with vitamin C-supplementation) and vitamin C-deficiency in guinea-pigs are associated with decreased collagen gene expression in connective tissues. Recently we presented evidence that circulating insulin-like growth factor binding protein (IGFBP)-1 and-2 that are induced during both nutritional deficiencies may be responsible for this inhibition by interfering with IGF-I action. The present objective was to determine whether circulating IGFBPs are accumulated in bone, skin and cartilage during fasting, which would support an endocrine role for them. IGFBP-1 mRNA was not detected in any of the connective tissues. The protein, as measured by ligand blotting, was not present in tissues of normal animals but accumulated early during fasting in all of the tissues. Bone and cartilage from normal animals contained IGFBP-2 and its mRNA, but only in bone did their levels increase during fasting. IGFBP-3 mRNA was not detected in connective tissues from normal or fasted guinea-pigs. Little or no IGFBP-3 was detected in normal tissue extracts, but protein accumulated during fasting and presumably was derived from the circulation. IGF-I and-II mRNAs were expressed in bone and cartilage but in skin, only IGF-II mRNA was detected. Affinity cross-linking revealed that in skin, IGFBP-3 contained relatively few unoccupied IGF-I binding sites compared to IGFBP-1 while in bone and cartilage, only IGFBP-1 contained unoccupied binding sites. IGFBP-1, acting by endocrine action, is probably the major factor responsible for inhibition of IGF-I-dependent collagen gene expression during fasting.

Populations de cellules extraites de reins et leur utilisation pour la réparation et le régénération de tissus

L'invention porte sur des populations de cellules extraites de tissus de reins de mammiferes ... more L'invention porte sur des populations de cellules extraites de tissus de reins de mammiferes isolees ou purifiees, sur des methodes d'isolement et de purification de ces populations de cellules, et sur des methodes de traitement de maladies renales par administration de ces populations de cellules a des mammiferes.

Zusammensetzung mit glycosaminogycanen und hyaluronidase-hemmern zur behandlung arthritischer gelenke

Nouveau peptide a activite osteogene

La presente invention concerne une composition comprenant un composant de peptide isole ou recomb... more La presente invention concerne une composition comprenant un composant de peptide isole ou recombinant qui a une activite de proliferation de cellules osteogenes. Le peptide, qui favorise la proliferation d'osteoblastes, est utile dans le traitement des fractures, en tant qu'element de remplissage de sites osseux deficients, pour inhiber le decroissement de la substance osseuse du a l'osteoporose et aux maladies parodontales, et dans la prevention des fractures associees a l'osteoporose ou a l'arthrite rhumatoide. Le peptide de l'invention, ou les cellules modifiees genetiquement pour produire le peptide, peut etre combine avec une matrice compatible avec les os afin de faciliter la liberation lente du peptide dans un site de traitement et/ou pour creer une structure de developpement de l'os.

Regeneration und reparatur von nervengewebe nach einer verletzung

Cellules dérivées de cordon ombilical post-partum pour l'utilisation dans le traitement de maladies du coeur et du système circulatoire

Regeneration and Repair of Neural Tissue Using

Journal of Experimental Orthopaedics

Purpose Injectable connective tissue matrices (CTMs) may promote tendon healing, given their mini... more Purpose Injectable connective tissue matrices (CTMs) may promote tendon healing, given their minimally invasive properties, structural and biochemical extracellular matrix components, and capacity to fill irregular spaces. The purpose of this study is to evaluate the effects of placental CTMs on the cellular activities of human tenocytes. Decellularization, the removal of cells, cell fragments, and DNA from CTMs, has been shown to reduce the host’s inflammatory response. Therefore, the authors hypothesize that a decellularized CTM will provide a more cell-friendly matrix to support tenocyte functions. Methods Three human placental CTMs were selected for comparison: AmnioFill® (A-CTM), a minimally manipulated, non-viable cellular particulate, BioRenew™ (B-CTM), a liquid matrix, and Interfyl® (I-CTM), a decellularized flowable particulate. Adhesion and proliferation were evaluated using cell viability assays and tenocyte migration using a transwell migration assay. Gene expression of ...