Human umbilical cord blood mesenchymal stem cells engineered to overexpress growth factors accelerate outcomes in hair growth

Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) are used in tissue repair and regeneration; however, the mechanisms involved are not well understood. We investigated the hair growth-promoting effects of hUCB-MSCs treatment to determine whether hUCB-MSCs enhance the promotion of hair growth. Furthermore, we attempted to identify the factors responsible for hair growth. The effects of hUCB-MSCs on hair growth were investigated in vivo, and hUCB-MSCs advanced anagen onset and hair follicle neogeneration. We found that hUCB-MSCs co-culture increased the viability and up-regulated hair induction-related proteins of human dermal papilla cells (hDPCs) in vitro. A growth factor antibody array revealed that secretory factors from hUCB-MSCs are related to hair growth. Insulin-like growth factor binding protein-1 (IGFBP-1) and vascular endothelial growth factor (VEGF) were increased in co-culture medium. Finally, we found that IGFBP-1, through the co-localization of an IGF-1 and IGFBP-1, had positive effects on cell viability; VEGF secretion; expression of alkaline phosphatase (ALP), CD133, and β-catenin; and formation of hDPCs 3D spheroids. Taken together, these data suggest that hUCB-MSCs promote hair growth via a paracrine mechanism.

Reduction of venous pressure during the resection of liver metastases compromises enteric blood flow: IGFBP-1 as a novel biomarker of intestinal barrier injury

OBJECTIVES: Disruption of the intestinal barrier and bacterial translocation commonly occur when intestinal blood flow is compromised. The aim of this study was to determine whether liver resection induces intestinal damage. METHODS: We investigated intestinal fatty-acid binding protein and insulin-like growth factor binding protein levels in the plasma of patients who underwent liver resection. RESULTS: We show that liver resection is associated with significant intestinal barrier injury, even if the Pringle maneuver is not performed. CONCLUSION: We propose the use of insulin-like growth factor binding protein-1 as a novel biomarker of intestinal damage in such situations.

Insulin-like Growth Factor Binding Protein-1/ alpha-fetoprotein versus Placental alpha microglobulin-1 for diagnosis of premature fetal membranes rupture.

Objectives: To compare insulin-like growth factor binding protein-1/alpha-fetoprotein (IGFBP-1/AFP) to placental alpha microglobulin-1 (PAMG-1) for diagnosis of premature fetal membranes rupture (PROM). Methods: 220 pregnant women ≥ 37 and < 39 weeks` gestation studied and classified into two groups; study group (PROM) and control group (no PROM). Examination of the studied women followed by abdominal ultrasound (TAS) and sterile vaginal speculum examination to visualize amniotic fluid leaking and for collection of samples for fern, nitrazine, AmniSure® and AmnioQuick® Duo+ tests on admission. Results: The sensitivity and specificity of AmnioQuick® Duo+ test to detect PROM was 93.6% and 86.4%; respectively compared to 95.5% and 89.1%; respectively for AmniSure® test, 72.7% and 80.9%; respectively for fern test and 76.4% and 83.6%; respectively for nitrazine test. PPV, NPV and accuracy of AmnioQuick® Duo+ test to detect PROM were 87.3%, 93.1% and 90%; respectively compared to 89.7, 95.1% and 92.3%; respectively for AmniSure® test, 79.2%, 74.8% and 76.8%; respectively for fern test and 82.4%, 77.97% and 80%; respectively for nitrazine test. AmnioQuick® Duo+ and AmniSure® tests had higher sensitivity, specificity, predictive values and accuracy to detect PROM compared to conventional diagnostic tests. Conclusion: AmnioQuick® Duo+ test for detection of IGFBP-1/AFP was rapid, accurate bedside test better than the individual conventional diagnostic tests and has same accuracy and performance like AmniSure® test.

Study of umbilical cord blood adiponectin, IGF-I, IGFBP-1, insulin and leptin levels in small for gestational age neonates at birth / 대한산부인과학회지

OBJECTIVE: Intrauterine growth is influenced by multiple factors like genetic, nutritional, environmental and hormonal factors. As birth weight is reported to be related to perinatal morbidity and mortality, we aimed to compare umbilical cord blood adiponectin, IGF-I, IGFBP-1, insulin and leptin levels between small for gestational age (SGA) and appropriate for gestational age (AGA) neonates at birth to investigate the influence of these factors on birth weight and ponderal index. METHODS: We investigated retrospectively 30 pregnant women with SGA and 30 pregnant women with AGA who delivered at Ewha Womans University Hospital and their babies from January 2007 to December 2007. Fetal umbilical cord venous blood adiponectin, IGF-I, IGFBP-1, insulin and leptin levels from SGA and AGA neonates were obtained at the time of delivery. The definition used to identify cases of SGA was individual birth weight ratio of less than 10th percentile and the definition of ponderal index (PI) was [BW (g)/ (height (cm))3]x100. RESULTS: Umbilical cord blood adiponectin, IGF-I and IGF/IGFBP ratio were significantly lower (P<0.05) in SGA than AGA. And umbilical cord blood IGFBP-1 were significantly higher (P<0.05) in SGA than AGA. But there was no significant difference in umbilical cord blood insulin and leptin levels between SGA and AGA neonates. Positive correlation was noted between adiponectin and IGF-I, IGF/IGFBP ratio, insulin and leptin. Negative correlation was noted between adiponectin and IGFBP-1, IGF-I and IGFBP-1. On multiple regression analysis, adiponectin and IGF-I were significant factors associated with body weight (BW), but only IGFBP-1 was significant factor associated with PI. CONCLUSION: These results suggest that fetal adiponectin, IGF-I, IGFBP-1 may have an important role in regulation of intrauterine growth and we will expect that evaluation of adiponectin and IGF-I in SGA may be helpful in prediction of neonatal outcome, and IGFBP-1 may be useful in diagnosis of asymmetric intrauterine growth retardation (IUGR).

The Correlation of Ovarian Follicular Concentrations of IGF-II, IGFBP-1, and 3 between Cumulative Embryo Score in Patients Undergoing IVF-ET / 대한산부인과학회잡지

OBJECTIVE: To investigate the correlation between the concentrations of insulin-like growth factor-II (IGF-II), insulin-like growth factor binding protein-1, 3 (IGFBP-1, 3) in the follicular fluid and the cumulative embryo score (CES) in the patient who underwent in vitro fertilization and embryo transfer (IVF-ET). MATERIALS AND METHODS: A total of 21 cycles of 18 patients which underwent IVF-ET cycle after controlled ovarian hyperstimulation (COH) were included in this study. Using immunoradiometric assay (IRMA), we measured the concentrations of IGF-II, IGFBP-1, 3 in the follicular fluid. The patients were grouped into the pregnant and non-pregnant group. The concentrations of IGF-II, IGFBP-1, 3 in the follicular fluid were compared between the two groups and the correlations of the follicular concentrations of IGF-II, IGFBP-1, 3 and cumulative embryo score were evaluated. Results were analyzed with Mann-Whitney U test and Spearman's rank correlation coefficient and statistical significance was defined as p<0.05. RESULTS: There were no statistical significance in the follicular concentrations of IGF-II, IGFBP-1, 3 between the pregnant group and non-pregnant group. There were signifiant correlation between the follicular concentration of IGF-II and cumulative embryo score (p=0.001). There might be correlations between the follicular concentration of IGFBP-3, and free IGF-II and cumulative embryo score (p=0.053, p=0.056, respectively). CONCLUSION: The follicular IGF-II and free IGF-II might have an influence to development of good- quality embryos in patients undergoing IVF-ET.

Measurement of Amniotic Fluid Nitric Oxide and Fetal Plasma Growth Factor Levels in Pregnancies Complicated by Intrauterine Growth Restriction with Normal Uterine Artery Doppler Velocimetry / 대한주산의학회잡지

OBJECTIVE: Our purpose was to evaluate the relationship between amniotic fluid nitric oxide(NO) and fetal blood IGF-I, IGFBP-1, and cortisol in pregnancies complicated by intrauterine growth restriction(IUGR), but showing normal uterine artery doppler waveform. METHODS: From July 1999 to March 2000, 18 pregnant women with IUGR and 18 normal pregnancies were studied. Both group showed normal uterine artery doppler waveform. Amniotic fluid samples were collected to measure NO, and fetal blood samples were collected from umbilical vein to measure fetal growth factors. The definition used to identify cases of IUGR depended on three criteria: clinical evidence of suboptimal growth, ultrasonographic evidence of deviation from an appropriate growth percentile, and individualized birth weight ratios <10th percentile. RESULTS: Overall median NO values in amniotic fluid were lower in IUGRs than in controls, but there was no statistical significance. However, IUGR newborns showed significantly lower(p<0.05) concentrations of IGF-I, and greater(p<0.05) concentrations of IGFBP-1 and cortisol than did controls. CONCLUSION: These result suggest that cord blood IGF-I, IGFBP-1, and cortisol, but not amniotic fluid NO may act major regulating factor in idiopathic IUGR without placental insufficiency.

Insulin-like Growth Factor-Binding Protein-1 in Cervical Secretion as a Predictor of Preterm Delivery / 대한산부인과학회잡지

OBJECTIVE: The phosphorylated isoforms of insulin-like growth factor-binding protein-1 (IGFBP-1) were produced by the decidua. The aim of this study was to evaluate whether the presence of phosphorylated IGFBP-1 (phIGFBP-1) in cervical secretions of pregnant women with preterm uterine contractions can predict an increased risk of preterm delivery and infectious complications. METHOD: The prospective study of 32 pregnant women who admitted under the diagnosis of preterm labor with intact membrane at gestational age of 24+0 to 36+0 weeks. Phsphorylated IGFBP-1 was qualitatively assayed using immunochromatography in cervical swab samples at the time of admission. The interval between the test and delivery, gestational age, duration of tocolysis, birth weight, CRP, ESR and the presence of neonatal infection were compared between positive and negative groups. RESULTS: There was no differnce in age, obstetric histories and gestational age and Bishop score at the time of admission between two groups. Eight pregnacies out of 13 positive group and two pregnacies out of 19 negative group resulted in preterm birth. The sensitivity and specificity of the phIGFBP-1 test to predict preterm birth were 80.0% and 77.3%, respectively. The mean getational age and interval between the test and delivery were 38.36 weeks and 45.0 days and 35.78 weeks and 35.46 days in negative and positive group respectively. The birth weight of the babies was significantly higher in negative group. The duration of tocolysis was longer in positive group with marginal statistical significance. The CRP, ESR and WBC count were not different. One postpartum sepsis, one neonatal death and one necrotizing enterocolitis were complicated in positive group. CONCLUSION: The presence of phIGFBP-1 is an usful marker to predict preterm birth in case of regular uterine contraction with intact fetal membranes.

Insulin-like Growth Factor-Binding Protein-1 in Cervical Secretion as a Predictor of Preterm Delivery / 대한산부인과학회잡지

OBJECTIVE: The phosphorylated isoforms of insulin-like growth factor-binding protein-1 (IGFBP-1) were produced by the decidua. The aim of this study was to evaluate whether the presence of phosphorylated IGFBP-1 (phIGFBP-1) in cervical secretions of pregnant women with preterm uterine contractions can predict an increased risk of preterm delivery and infectious complications. METHOD: The prospective study of 32 pregnant women who admitted under the diagnosis of preterm labor with intact membrane at gestational age of 24+0 to 36+0 weeks. Phsphorylated IGFBP-1 was qualitatively assayed using immunochromatography in cervical swab samples at the time of admission. The interval between the test and delivery, gestational age, duration of tocolysis, birth weight, CRP, ESR and the presence of neonatal infection were compared between positive and negative groups. RESULTS: There was no differnce in age, obstetric histories and gestational age and Bishop score at the time of admission between two groups. Eight pregnacies out of 13 positive group and two pregnacies out of 19 negative group resulted in preterm birth. The sensitivity and specificity of the phIGFBP-1 test to predict preterm birth were 80.0% and 77.3%, respectively. The mean getational age and interval between the test and delivery were 38.36 weeks and 45.0 days and 35.78 weeks and 35.46 days in negative and positive group respectively. The birth weight of the babies was significantly higher in negative group. The duration of tocolysis was longer in positive group with marginal statistical significance. The CRP, ESR and WBC count were not different. One postpartum sepsis, one neonatal death and one necrotizing enterocolitis were complicated in positive group. CONCLUSION: The presence of phIGFBP-1 is an usful marker to predict preterm birth in case of regular uterine contraction with intact fetal membranes.

Serum IGF-I, Free IGF-I, IGFBP-1, IGFBP-3 Levels in Children with Intrauterine Growth Retardation / 대한소아내분비학회지

PURPOSE:Most but not all intrauterine growth retardation(IUGR) children has catch-up growth postnatally. However, nothing is known about the predictive parameters on the catch-up growth. The aim of this study was to describe serum IGF-I, free IGF-I, IGFBP-1, and IGFBP-3 levels in IUGR children and to correlate these hormone values with auxologic parameters to investigate their value on the postnatal growth pattern. METHODS:Among children with IUGR born at Ewha Womans University from Jan. 1995 to Aug. 1998, 16 children with IUGR at 3 years of age and 12 age-matched normal controls were studied for auxologic and biologic parameters. We measured height, weight, and serum levels of insulin-like growth factor(IGF)-I, free IGF-I, IGF binding protein(BP)-1, IGFBP-3 using immunoradiometric kits. RESULTS: 1)Among 16 children with IUGR at 3 years of age, 13 children had catch-up growth(81.3%), but 3 children remained short stature(18.7%). The height standard deviation score(SDS) in children with IUGR and control were -0.3+/-0.8 and 0.8+/-0.7, respectively(P0.05). 2)Serum IGF-I levels in children with IUGR at 3 years of age and normal control were 90.9+/-35.4ng/mL and 68.4+/-24.4ng/mL, respectively(p>0.05) and free IGF-I were 0.9+/-0.5ng/mL and 0.6+/-0.3ng/mL(p>0.05), IGFBP-1 were 50.5+/-30.5ng/ mL and 52.3+/-23.2ng/mL(p>0.05), IGFBP-3 were 4,116.7+/-1,062.2ng/mL and 4,058.4+/-808.5ng/mL(p>0.05), respectively. 3)In children with IUGR at 3 years of age, height SDS in IUGR children with catch-up growth and those without catch-up growth were 0.002+/-0.6 and -1.5+/-0.7, respectively(P<0.001), but there were no differences in weight SDS, body mass index, IGF-I, free IGF-I, IGFBP-1 and IGFBP-3. 4)There were no significant correlations between height gain and any growth factors. CONCLUSION: The results show that there is no difference in the levels of IGF-I, free IGF-I, IGFBP-1 and IGFBP-3 in IUGR children at 3 years of age compared to age-matched normal control, suggesting that other factors rather than IGF-I, free IGF-I, IGFBP-1, IGFBP-3 may cause short stature in IUGR.

Growth Status and Levels of Growth Factors in Children with Insulin-dependent Diabetes Mellitus

PURPOSE: It is well known that the linear growth velocity in children with insulin-dependent diabetes mellitus (type 1 DM) is closely related to metabolic control and onset age of the disease. Many studies have demonstrated growth impairment in children with type 1 DM, regardless of the degree of metabolic control, whereas other studies have found no growth retardation. Therefore, we examined the growth status and the level of growth factors in children with type 1 DM, and compared them with healthy children. METHODS: Thirty-six patients with type 1 DM (21 female, 15 male; mean age, 10.8 years : range, 5-15 years)were studied. The mean duration of type 1 DM in these patients was 2.7 years (range, 0.1-7.0 years). Their growth status in height standard deviation score (HTSDS) and levels of insulin-like growth factor (IGF)-I, free IGF-I, IGF-II and IGF-binding protein (IGFBP)-3 were compared with age and sex matched normal children (21 female, 15 male; mean age, 10.3 years; range, 5-15 years). RESULTS: As HTSDS in type 1 DM, children were 0.4 +/- 1.1, no prominent growth impairment was observed in type 1 DM children. IGF-I and IGF-II levels decreased significantly in type 1 DM, but no significant differences in free IGF-I and IGFBP-3 levels compared to normal. Height in type 1 DM children was in direct correlation with free IGF-I (r=0.35, P<0.05) and IGFBP-3 (r= 0.45, P<0.01), respectively. CONCLUSION: This study reveals that the levels of IGF-I and -II are decreased in children with type 1 DM, whereas free IGF-I levels are not. These findings may be related to the decreased IGFBP-3 levels in diabetic children, and may explain no growth impairment, except in cases of extremely poor metabolic control.

Growth Status and Levels of Growth Factors in Children with Insulin-dependent Diabetes Mellitus

PURPOSE: It is well known that the linear growth velocity in children with insulin-dependent diabetes mellitus (type 1 DM) is closely related to metabolic control and onset age of the disease. Many studies have demonstrated growth impairment in children with type 1 DM, regardless of the degree of metabolic control, whereas other studies have found no growth retardation. Therefore, we examined the growth status and the level of growth factors in children with type 1 DM, and compared them with healthy children. METHODS: Thirty-six patients with type 1 DM (21 female, 15 male; mean age, 10.8 years : range, 5-15 years)were studied. The mean duration of type 1 DM in these patients was 2.7 years (range, 0.1-7.0 years). Their growth status in height standard deviation score (HTSDS) and levels of insulin-like growth factor (IGF)-I, free IGF-I, IGF-II and IGF-binding protein (IGFBP)-3 were compared with age and sex matched normal children (21 female, 15 male; mean age, 10.3 years; range, 5-15 years). RESULTS: As HTSDS in type 1 DM, children were 0.4 +/- 1.1, no prominent growth impairment was observed in type 1 DM children. IGF-I and IGF-II levels decreased significantly in type 1 DM, but no significant differences in free IGF-I and IGFBP-3 levels compared to normal. Height in type 1 DM children was in direct correlation with free IGF-I (r=0.35, P<0.05) and IGFBP-3 (r= 0.45, P<0.01), respectively. CONCLUSION: This study reveals that the levels of IGF-I and -II are decreased in children with type 1 DM, whereas free IGF-I levels are not. These findings may be related to the decreased IGFBP-3 levels in diabetic children, and may explain no growth impairment, except in cases of extremely poor metabolic control.

A study on the relationship between diabetes chronic complications and the levels of serum IGF-1, IGFBP-1 and GH / 中国糖尿病杂志

Objective To explore the effects of insulin-like growth factor-l (IGF-l),insulin-like growth factor binding protein-1 (IGFBP-1) and growth hormone (GH) on the generation, development and treatment of diabetes chronic complications. Methods 20 healthy controls,10 type 1 diabetes mellitus patients and 62 type 2 diabetes mellitus patients were enrolled into the study. IGF-1, IGFBP-1, GH, HbAlc. serum insulin (INS) and serum C-peptide (C-P) were measured. Results ①Serum level of IGF-1 was obviously lower in the diabetes mellitus group than that in controls (type 1 P＜0. 05,type 2 P＜0. 05). ②Serum level of IGFBP-1 was significantly higher in type I diabetes mellitus than that in controls (P＜0. 05),and it was obviously lower in type 2 diabetes mellitus with obesity and hyperinsulinism than that in contris (P＜0. 05). ③Serum level of GH was higher in type 1 diabetes mellitus than that in controls (P＜0. 05 ) and was not significantly different from that in controls (P＞0. 05). ④The level of IGF-l was higher in diabetes nephropathy (DN) patients and diabetes retinopathy (DR) patients than that in controls (P＜0. 05). ⑤The level of IGF1 was negatively correlated with HbAlc (P＜0. 01, type 1r=- 0.73, type 2r=-0. 62). Conclusion Measurement of IGF-1, IGFBP-1 and GH may play an important role in diabetes chronic complications,especially in the generation,development of diabetic microvascular.