IGF-1 loaded injectable microspheres for potential repair of the infarcted myocardium

2020 ◽  
pp. 088532822094850
Author(s):  
Elisabetta Rosellini ◽  
Niccoletta Barbani ◽  
Caterina Frati ◽  
Denise Madeddu ◽  
Diana Massai ◽  
...  
Keyword(s):  
Cell Culture ◽  
Growth Factor ◽  
In Situ Polymerization ◽  
Chemical Imaging ◽  
Homogeneous Distribution ◽  
Insulin Like Growth Factor ◽  
Gelatin Microspheres

The use of injectable scaffolds to repair the infarcted heart is receiving great interest. Thermosensitive polymers, in situ polymerization, in situ cross-linking, and self-assembling peptides are the most investigated approaches to obtain injectability. Aim of the present work was the preparation and characterization of a novel bioactive scaffold, in form of injectable microspheres, for cardiac repair. Gellan/gelatin microspheres were prepared by a water-in-oil emulsion and loaded by adsorption with Insulin-like growth factor 1 to promote tissue regeneration. Obtained microspheres underwent morphological, physicochemical and biological characterization, including cell culture tests in static and dynamic conditions and in vivo tests. Morphological analysis of the microspheres showed a spherical shape, a microporous surface and an average diameter of 66 ± 17µm (under dry conditions) and 123 ± 24 µm (under wet conditions). Chemical Imaging analysis pointed out a homogeneous distribution of gellan, gelatin and Insulin-like growth factor-1 within the microsphere matrix. In vitro cell culture tests showed that the microspheres promoted rat cardiac progenitor cells adhesion, and cluster formation. After dynamic suspension culture within an impeller-free bioreactor, cells still adhered to microspheres, spreading their cytoplasm over microsphere surface. Intramyocardial administration of microspheres in a cryoinjury rat model attenuated chamber dilatation, myocardial damage and fibrosis and improved cell homing. Overall, the findings of this study confirm that the produced microspheres display morphological, physicochemical, functional and biological properties potentially adequate for future applications as injectable scaffold for cardiac tissue engineering.

scholarly journals O efeito molecular e estrutural do hormônio tiroideano no esqueleto

2004 ◽  
Vol 48 (1) ◽  
pp. 183-195 ◽  
Author(s):  
Cecília H.A. Gouveia
Keyword(s):  
Growth Factor ◽  
Insulin Like Growth Factor ◽  
Receptores Nucleares

O hormônio tiroideano é essencial para o desenvolvimento, maturação e metabolismo ósseos normais. Durante o desenvolvimento, a deficiência do hormônio tiroideano resulta em atraso na maturação do esqueleto e disgênese das epífises, resultando em redução do crescimento e anormalidades esqueléticas. O hormônio tiroideano também tem efeito no osso do adulto. A tirotoxicose é freqüentemente associada ao aumento do metabolismo ósseo e diminuição da massa óssea. Embora a importância do hormônio tiroideano no desenvolvimento e metabolismo ósseos seja clara, os mecanismos que medeiam os efeitos desse hormônio no tecido ósseo apenas começam a ser desvendados. O hormônio tiroideano pode atuar indiretamente no esqueleto, aumetando a secreção de hormônio do crescimento (GH) e insulin-like growth factor-1 (IGF-1); ou diretamente, modulando genes alvo via receptores nucleares específicos. Não se sabe, entretanto, se os principais efeitos do hormônio tiroideano no osso são resultado de ações diretas ou indiretas. Achados in vitro, tais como a presença de receptores de hormônio tiroideano (TR) e a indução de genes e proteínas em células esqueléticas pelo hormônio tiroideano, evidenciam a importância de ações diretas. Esta revisão tem como meta sumarizar os achados in vivo e in vitro relacionados aos efeitos do hormônio tiroideano no esqueleto.

Stem cell defects in parthenogenetic peri-implantation embryos

Development ◽  
1995 ◽  
Vol 121 (7) ◽  
pp. 2069-2077
Author(s):  
E.D. Newman-Smith ◽  
Z. Werb
Keyword(s):  
Stem Cells ◽  
Growth Factor ◽  
Inner Cell Mass ◽  
Cell Mass ◽  
Cell Types ◽  
Insulin Like Growth Factor ◽  
Embryonic Antigen ◽  
Parietal Endoderm

Mouse embryos containing only maternal chromosomes (parthenotes) develop abnormally in vivo, usually failing at the peri-implantation stage. We have analyzed the development of parthenote embryos by using an inner cell mass (ICM) outgrowth assay that mimics peri-implantation development. ICMs from normal embryos maintained undifferentiated stem cells positive for stage-specific embryonic antigen-1 and Rex-1 while differentiating into a variety of cell types, including visceral endoderm-like cells and parietal endoderm cells. In contrast, ICMs from parthenotes failed to maintain undifferentiated stem cells and differentiated almost exclusively into parietal endoderm. This suggests that parthenote ICMs have a defect that leads to differentiation, rather than maintenance, of the stem cells, and a defect that leads to a parietal endoderm fate for the stem cells. To test the hypothesis that the ICM population is not maintained owing to a lack of proliferation of the stem cells, we investigated whether mitogenic agents were able to maintain the ICM population in parthenotes. When parthenote blastocysts were supplied with the insulin-like growth factor-1 receptor (Igf-1r) and insulin-like growth factor-2 (Igf-2), two genes not detectable in parthenote blastocysts by in situ hybridization, the ICM population was maintained. Similarly, culture of parthenote blastocysts in medium conditioned by embryonic fibroblasts and supplemented with the maternal factor leukemia inhibitory factor maintained the ICM population. However, once this growth factor-rich medium was removed, the parthenote ICM cells still differentiated predominantly into parietal endoderm.(ABSTRACT TRUNCATED AT 250 WORDS)

Temporal changes in the expression of the insulin-like growth factor II gene associated with tissue maturation in the human fetus

Development ◽  
1989 ◽  
Vol 106 (3) ◽  
pp. 543-554 ◽  
Author(s):  
A.L. Brice ◽  
J.E. Cheetham ◽  
V.N. Bolton ◽  
N.C. Hill ◽  
P.N. Schofield
Keyword(s):  
Growth Factor ◽  
Cell Types ◽  
Specific Cell ◽  
Insulin Like Growth Factor ◽  
Vitro Fertilization ◽  
Age Related ◽  
Factor Ii ◽  
Metanephric Blastema

The insulin-like growth factors are broadly distributed in the human conceptus and are thought to play a role in the growth and differentiation of tissues during development. Using in situ hybridization we have shown that a wide variety of specific cell types within tissues express the gene for insulin-like growth factor II at times of development from 18 days to 14 weeks of gestation. Examination of blastocysts produced by in vitro fertilization showed no expression, thus bracketing the time of first accumulation of IGF-II mRNA to between 5 and 18 days postfertilization. The pattern of IGF-II expression shows specific age-related differences in different tissues. In the kidney, for example, expression is found in the cells of the metanephric blastema which is dramatically reduced as the blastema differentiates. The reverse is also seen, and we have noted an increase in expression of IGF-II in the cytotrophoblast layer of the placenta with gestational age. The sites of expression do not correlate with areas of either high mitotic activity or specific types of differentiation, but the observed pattern of expression in the kidney, adrenal glands and liver suggests an explanation for the abnormally high IGF-II mRNA expression in developmental tumours such as Wilms' tumour.

Transport of Insulin-Like Growth Factor 1 in Intervertebral Disc: Effect of Binding Interactions and Inhomogeneous Distribution of Binding Proteins in Annulus Fibrosus and Nucleus Pulposus

2010 ◽  
Author(s):  
Francesco Travascio ◽  
Chun Yuh Huang ◽  
Wei Yong Gu
Keyword(s):  
Growth Factor ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Reactive Transport ◽  
Binding Proteins ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins ◽  
Binding Interactions

The intervertebral disc (IVD), being the largest avascular structure in human body, receives nourishment from the vascular network present near its periannular surface and at cartilage endplates (CEPs). It is believed that insufficient nutritional supply is a major cause for disc degeneration [1]. Understanding the mechanisms of solute transport in IVD is crucial for elucidating the etiology of disc degeneration, and to develop strategies for tissue repair (in vivo), and tissue engineering (in vitro). Transport in IVD is complex and involves a series of electromechanical, chemical, and biological coupled events. This study focused on the implications of solute-tissue reversible binding reactions on transport phenomena in the disc. A two dimensional (2D) finite element model was developed to predict diffusive-reactive transport in IVD. The numerical model was used to simulate transport of insulin-like growth factor 1 (IGF-1) in IVD, in the presence of binding interactions between IGF-1 and IGF-binding proteins (IGFBP-3) located on the extracellular matrix (ECM) of the disc.

scholarly journals Modulation of 11β-Hydroxysteroid Dehydrogenase Isozymes by Growth Hormone and Insulin-Like Growth Factor: In Vivo and In Vitro Studies1

1999 ◽  
Vol 84 (11) ◽  
pp. 4172-4177 ◽  
Author(s):  
J. S. Moore ◽  
J. P. Monson ◽  
G. Kaltsas ◽  
P. Putignano ◽  
P. J. Wood ◽  
...  
Keyword(s):  
Growth Factor ◽  
Reductase Activity ◽  
Primary Cultures ◽  
Inverse Correlation ◽  
Hydroxysteroid Dehydrogenase ◽  
Insulin Like Growth Factor ◽  
Igf I ◽  
Glucose Output

The interconversion of hormonally active cortisol (F) and inactive cortisone (E) is catalyzed by two isozymes of 11β-hydroxysteroid dehydrogenase (11βHSD), an oxo-reductase converting E to F (11βHSD1) and a dehydrogenase (11βHSD2) converting F to E. 11βHSD1 is important in mediating glucocorticoid-regulated glucose homeostasis and regional adipocyte differentiation. Earlier studies conducted with GH-deficient subjects treated with replacement GH suggested that GH may modulate 11βHSD1 activity. In 7 acromegalic subjects withdrawing from medical therapy (Sandostatin-LAR; 20–40 mg/month for at least 12 months), GH rose from 7.1 ± 1.5 to 17.5 ± 4.3 mU/L (mean ± se), and insulin-like growth factor I (IGF-I) rose from 43.0 ± 8.8 to 82.1 ± 13.7 nmol/L (both P < 0.05) 4 months after treatment. There was a significant alteration in the normal set-point of F to E interconversion toward E. The fall in the urinary tetrahydrocortisols/tetrahydocortisone ratio (THF+allo-THF/THE; 0.82 ± 0.06 to 0.60 ± 0.06; P < 0.02) but unaltered urinary free F/urinary free E ratio (a marker for 11βHSD2 activity) suggested that this was due to inhibition of 11βHSD1 activity. An inverse correlation between GH and the THF+allo-THF/THE ratio was observed (r = −0.422; P < 0.05). Conversely, in 12 acromegalic patients treated by transsphenoidal surgery (GH falling from 124 ± 49.2 to 29.3 ± 15.4 mU/L; P < 0.01), the THF+allo-THF/THE ratio rose from 0.53 ± 0.06 to 0.63 ± 0.07 (P < 0.05). Patients from either group who failed to demonstrate a change in GH levels showed no change in the THF+allo-THF/THE ratio. In vitro studies conducted on cells stably transfected with either the human 11βHSD1 or 11βHSD2 complementary DNA and primary cultures of human omental adipose stromal cells expressing only the 11βHSD1 isozyme indicated a dose-dependent inhibition of 11βHSD1 oxo-reductase activity with IGF-I, but not GH. Neither IGF-I nor GH had any effect on 11βHSD2 activity. GH, through an IGF-I-mediated effect, inhibits 11βHSD1 activity. This reduction in E to F conversion will increase the MCR of F, and care should be taken to monitor the adequacy of function of the hypothalamo-pituitary-adrenal axis in acromegalic subjects and in GH-deficient, hypopituitary patients commencing replacement GH therapy. Conversely, enhanced E to F conversion occurs with a reduction in GH levels; in liver and adipose tissue this would result in increased hepatic glucose output and visceral adiposity, suggesting that part of the phenotype currently attributable to adult GH deficiency may be an indirect consequence of its effect on tissue F metabolism via 11βHSD1 expression.

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