Advanced Maturation Research Articles

PREHARVEST AVG AND KAOLIN AND POSTHARVEST 1-MCP APPLICATION EFFECTS ON ADVANCED MATURITY PEACH QUALITY AND STORAGE

Treatments to conserve quality for long-distance transportation were studied with advanced maturity 'Royal Glory' peaches and 'Caldesi 2000' nectarines. Kaolin (Surround) was applied at commercial rates 3 times every 10 days until harvest; AVG (ReTain) was also applied 10 days before anticipated harvest at 0.1% active ingredient + 0.01% surfactant; and 1250 μl L -1 1-MCP (SmartFresh) was applied immediately after harvest. Fruit quality was evaluated at harvest and after 1, 2 and 4 weeks storage in perforated PE bags at 2°C, 90-95% RH plus 1 day shelf life. Kaolin application had no effect on flesh firmness and overall fruit eating quality in both cultivars at harvest and during storage. Fruit from AVG treated trees were harder and had higher acidity than and similar soluble solids content (SSC) and flesh color to fruit from control trees at harvest. These effects disappeared after the 1 st week of cold storage resulting in quality similar to control fruit from the 2 nd week of storage. Postharvest 1-MCP application resulted in fruit harder than the control fruit at harvest and throughout the storage period with firmness able to withstand long distance transportation. 1-MCP treatment had no other effects on the organoleptic quality of these advanced maturity fruit throughout the 4 weeks cold storage. No chilling injury symptoms were observed at any time or treatment to an extent of degrading fruit quality.

QUALITY OF STARFRUIT HARVESTED AT ADVANCED MATURITY STAGE

A study was carried out to compare the quality of starfruit harvested at commercial maturity or colour index 2 (fruit colour is light green with tinge of yellow) with those harvested at an advanced maturity stage or colour index 4 (about 50% of fruit surface had turned to a golden colour). Fruit of advanced maturity showed better colour, chemical compositions and sensory quality as compared to those harvested at the commercial stage. The advanced maturity fruit could be stored for up to 8 weeks at 8°C.

DEFICIT IRRIGATION AND REFLECTIVE MULCH EFFECTS ON PEACH AND NECTARINE FRUIT QUALITY AND STORAGE ABILITY

The effects of deficit irrigation and reflective mulch were studied as possible means to reduce irrigation water use and improve peach fruit quality and storage ability. 'Royal Glory' peach and 'Caldesi 2000' nectarine trees were drip irrigated close to ETc (control) or with 50% of ETc (deficit) during the last three weeks before anticipated harvest of tree-ripe fruit. Reflective Extenday ® mulch was also applied on the tree row for almost a month before anticipated harvest at control or deficit irrigated trees. Fruit quality from the upper and lower parts of the tree was evaluated at harvest and after 2, 4 and 6 weeks at 2°C plus 1 day shelf life. Fruit quality included skin color, flesh firmness, specific conductivity and dry matter (DM), juice soluble solids content (SSC), acidity and total phenols (TP) and subjective evaluation of chilling injury (CI) symptoms (flesh leatheriness and browning). With storage time and in both cultivars, fruit skin only slightly changed, fruit flesh softened, specific conductivity, SSC, acidity and DM decreased and TP content and CI (mainly leatheriness) increased. With deficit irrigation or reflective mulch, the two cultivars behaved differently. Nectarines from deficit irrigated trees had improved quality but lower storage ability than fruit from control trees. Peaches from deficit irrigated trees had similar quality to control fruit except of higher SSC (mainly the fruit from the lower part of the canopy) and slightly higher Cl. Nectarines from reflective mulched trees had better skin color, harder flesh, higher acidity and DM, similar SSC and TP and higher leatheriness incidence than fruit from control trees. Peaches from reflective mulched trees had the most advanced maturity fruit at harvest compared to the other treatments, and higher quality fruit but also lower storage ability than control fruit. In short, fruit quality of both cultivars studied was improved due to deficit irrigation or reflective mulching but their storage ability was reduced from these treatments.

594 Early Prediction of Long Term Outcome of Low Risk Premature Neonates with the Aeeg

Background and aims: Preterm infants of lower gestational age(GA) display advanced maturation of aEEG in comparison to others of higher GA at the same post conceptional age(PCA). Brain ontogeny follows specific developmental stages and any deviations from this process may influence later cognitive function.To investigate the association between aEEG evolution during the neonatal period and outcome of premature infants with different GA.Methods: 84 clinically stable preterm infants(GA 26-32 wks) without ultrasonographic evidence of neurological abnormalities at birth were assessed at the age of 3 years (Bayleys screening test, III edition) aEEG traces of all neonates were recorded within the first 72 h of life and then weekly until discharge. Four aspects of each tracing (continuity, sleep-wake cycling, bandwidth, and amplitude of the lower border)were evaluated applying pre-established criteria.Results: None of the children had gross motor disturbances, but one, and severe developmental delays. The children were divided into group A (n=23, mild developmental problems) and group B(n=61 normal for the age). Both groups had comparable initial neonatal characteristics. Group A showed higher scores in all 4 components of the aEEG as compared to group B, with significant differences around 31-32 wks PCA. Total score(T) of the 4 aspects of aEEG was significantly higher between 28-32wks (figure).Conclusions: Accelerated maturation of cerebral function seems to be associated with long-term cognitive and behavioral deficits without overt effects on motor development in preterm infants who were neurologically normal in the neonatal period.

CANT1 mutation is also responsible for Desbuquois dysplasia, type 2 and Kim variant

BackgroundDesbuquois dysplasia (DD) is a recessively inherited condition characterised by short stature, generalised skeletal dysplasia and advanced bone maturation. DD is both clinically and radiographically heterogeneous, and two subtypes have...

Pathologic basis of echogenic cystic lesions in the human placenta: Role of ultrasound-guided wire localization

Objective The sonographic appearance of the placenta is normally homogenous throughout the second trimester. A variety of abnormalities in placental texture have been described, some of which may be pathologic and associated with adverse clinical outcomes. We characterized the pathologic basis of one lesion termed echogenic cystic lesions (ECLs) that may be a prognostic marker in intrauterine growth restriction (IUGR). Study design We retrospectively correlated placental pathology in 50 pregnancies that had a total of 84 ECLs documented by ultrasound prior to delivery. Six additional women with placental ECLs prospectively underwent immediate post-delivery ultrasound-guided wire localization of 9 lesions followed by placental pathology. Obstetric outcome data were recorded. Results Severe pre-eclampsia (20%) and extreme IUGR (18%) were common outcomes. Of 93 ECLs identified, 46 (49%) gross lesions were found by placental pathology. Inter-villous thrombosis was the most significant lesion found (30/46, 65%) compared to all other lesions (35%; Z-Test, p = 0.007). Ultrasound guidance identified 8/9 (89%) lesions of which 6/8 (67%) were inter-villous thrombosis. Associated lesions (infarction, 36%; advanced villous maturation, 27%) and small placental weight (<10th centile, 38%) were present in 50%, but did not increase the risk of adverse perinatal outcome. Conclusions ECLs are most commonly due to inter-villous thrombosis. The adverse clinical outcomes may be mediated by associated lesions not readily detectable by ultrasound. Ultrasound-guided wire localization is a promising research tool for future large-scale cohort studies needed to define the clinical utility of placental ultrasound findings.

Collapse of the reproductive process of two migratory fish (Prochilodus argenteus and Prochilodus costatus) in the Três Marias Reservoir, São Francisco River, Brazil

Summary Generally, migratory fish can complete vitellogenesis even when the migration process is interrupted; however, final oocyte maturation does not occur and therefore there is no spawning. To evaluate the reproductive process of migratory fish inside the reservoir of the Tres Marias Dam (a lentic environment), 90 female and 81 male Prochilodus argenteus and 172 female and 115 male Prochilodus costatus were captured in this environment. Males and females from both species in the resting stage were pre-dominant, and the highest frequency of specimens in advanced maturation stages occurred in November, December and January. According to histological analysis, ovarian regression was frequent and vitellogenic oocytes undergoing atresia were intensely observed, moreover, no fish with ovaries and testes with characteristics of spawning and spermiation, respectively, were captured. This indicated that both species were preparing for reproduction and reaching advanced gonad maturation, but were unable to complete the process of reproduction in this environment. The data from this study indicate that the modification of portions of rivers to lentic environments can have a negative impact on the reproductive process of migratory fish in freshwater.

Aplicação de 1-metilciclopropeno e absorção de etileno em maçã da cultivar 'Royal Gala' colhida tardiamente

O objetivo deste trabalho foi avaliar a perda da eficiência do controle do etileno com o uso de 1-MCP e da sua absorção ao longo do período de oito meses de armazenamento em atmosfera controlada (AC) de maçãs da cultivar 'Royal Gala' colhidas em estádio de maturação avançado. Os frutos foram colhidos com firmeza da polpa de 89,5N; índice de iodo-amido de 6,7; acidez de 5,06meq 100mL-1; teor de sólidos solúveis de 11,8°Brix; produção de etileno de 0,721µL C2H4 kg-1 h-1; e respiração de 6,61mL CO2 kg-1 h-1. O delineamento experimental utilizado foi o inteiramente casualizado, com quatro tratamentos e seis repetições. Os frutos foram armazenados na temperatura de 0,5°C (±0,1), sendo avaliadas as seguintes condições: [1] AC com 1,2kPa O2 + 2,5kPa CO2; [2] AC com aplicação de 1µL L-1 de 1-MCP; [3] AC com aplicação de 1µL L-1 de 1-MCP e de 10µL L-1 de etileno (AE); e [4] AC com baixa concentração de etileno (&lt;0,1µL L-1) (BE). O 1-MCP não apresentou eficiência na conservacão da firmeza da polpa em maçãs colhidas em estádio de maturação avançado, mas manteve eficiência na redução da atividade da enzima ACC oxidase, produção de etileno e atividade respiratória dos frutos.

Effects of laser photherapy on bone defects grafted with mineral trioxide aggregate, bone morphogenetic proteins, and guided bone regeneration: A Raman spectroscopic study

We have used Raman analysis to assess bone healing on different models. Benefits on the isolated or combined use of mineral trioxide aggregate, bone morphogenetic proteins, guided bone regeneration and laser on bone repair have been reported, but not their combination. We studied peaks of hydroxyapatite and CH groups on defects grafted with MTA, treated or not with laser, BMPs, and GBR. Ninety rats were divided in 10 groups each, subdivided into three subgroups. Laser (λ850 nm) was applied at every other day for 2 weeks. Raman readings were taken at the surface of the defect. Statistical analysis (CHA) showed significant differences between all groups (p = 0.001) and between Group II and all other (p < 0.001), but not with Group X (p = 0.09). At day 21 differences were seen between all groups (p = 0.031) and between Groups VIII and X when compared with Groups VI (p = 0.03), V (p < 0.001), IV (p < 0.001), and IX (p = 0.04). At the end of the experimental period no significant differences were seen. On regards CH, significant differences were seen at the 15(th) day (p = 0.002) and between Group II and all other groups (p < 0.0001) but not with control. Advanced maturation on irradiated bone is because of increased secretion of calcium hydroxyapatite (CHA) that is indicative of greater calcification and resistance of the bone. We conclude that the association of the MTA with laser phototherapy (LPT) and/or not with GBR resulted in a better bone repair. The use of the MTA associated to IR LPT resulted in a more advanced and quality bone repair.

ORIGINAL ARTICLE: Effects of variety, sowing season and maturity stage on ruminal phosphorus release from whole maize stover and its morphological fractions

An in situ degradation technique was used to investigate the effects of variety, season and maturity stage on ruminal Phosphorus (P) release from whole maize stover and morphological fractions from five varieties of maize (conventional maize, CM; sweet maize, SM; waxy maize, WM; high oil maize, HOM; and fodder maize, FM). Maize plants were harvested in 2005, 17 and 31 days after tasselling and manually separated into leaf blade, leaf sheath, stem and husk. Results showed that the values of rapidly released P fractions (a), slowly released P fractions (b), rate constant of P release for fraction b (c) and effective disappearance (ED) of P were significantly influenced by variety, sowing season and maturity stage (p < 0.05). The ED of P in whole maize stover among the varieties decreased in the following order: FM (89.8%) > HOM (87.9%) > CM (87.0%) > SM (86.9%) > WM (83.9%). Advanced maturity stage increased (p < 0.001) the a and ED values of P in the leaf blade and leaf sheath, but decreased (p < 0.001) these parameters in the husk. The a fraction and ED of P were higher (p < 0.001) for maize sown in spring than those sown in summer. Significant (p < 0.05) interactions among variety, sowing season and maturity stage were noted in the a and ED values of P. Effective disappearance of morphological fraction varied significantly (p < 0.001) and followed the order: stem (90.3%) > leaf sheath (88.2%) > leaf blade (85.2%) > husk (84.9%). In conclusion, most of P in maize stover could be released in the rumen. The potential pollution resulting from P excretion in faeces may be alleviated, when maize stover is largely used as the main forage source of ruminants.

Discrimination of U-14 Soccer Players by Level and Position

Adolescence is often viewed as a critical period for selection in youth soccer. The present study compared the characteristics of regionally selected and non-selected under-14 players (U-14) as a group and by position. Players were classified as local (n=69) and regional (n=45). Weight, height, skinfolds, functional capacities, soccer skills and goal orientation were measured and skeletal age was assessed with the Fels method. Factorial ANOVA was used to test the effect of selection, position and respective interaction terms, while discriminant analysis was used to identify the variables that contributed to selection. Selected players had an advanced maturity status (F=24.97, p<0.01), were heavier (F=30.67, p<0.01) and taller (F=35.07, p<0.01); performed better in explosive power (F=21.25, p<0.01), repeated sprints (F=20.04, p<0.01) and ball control (F=3.69, p<0.05); and were more ego oriented (F=13.29, p<0.01). The 2 competitive groups did not differ in agility, aerobic endurance, dribbling, shooting, passing, and task orientation. Position-related variation was negligible. The percentage of players who were correctly classified in the original groups was slightly lower when the analysis was performed for the total sample (86%) than by position (86-90%). Future research on talent identification and selection should adopt a multidimensional approach including variables related to the physiological, perceptual, cognitive and tactical demands.

Cyclooxygenase-2 network as predictive molecular marker for clinical pregnancy in in vitro fertilization

The gene expression of human endometrium on the day of oocyte retrieval of pregnant and nonpregnant patients in a stimulated IVF cycle was compared in two independent groups with different GnRH-antagonist ovarian stimulation protocols. The present data suggest that increased gene expression of cyclooxygenase-2, together with the expression of other molecules in the cyclooxygenase-2 network, on the day of oocyte retrieval in GnRH-antagonist cycles coincides with a lower probability of achieving a clinical pregnancy in this cycle.

Composição bromatológica e digestibilidade de cana-de-açúcar colhida em duas épocas do ano

Objetivou-se com este estudo avaliar o efeito da época de corte sobre a composição bromatológica e digestibilidade in vitro de genótipos de cana-de-açúcar, comparar a composição bromatológica e digestibilidade in vitro das frações colmo e folhas, e estabelecer possíveis correlações entre composição química e digestibilidade in vitro da planta inteira de genótipos da cana-de-açúcar. Nove genótipos foram colhidos em maio e setembro de 2006. Em maio, somente a fração planta inteira foi analisada, em setembro foram separados em colmos, folhas ou planta inteira para determinação da composição bromatológica, sacarose (POL) e digestibilidade in vitro. Colmos apresentaram menor teor de fibra em detergente neutro (FDN) e lignina na MS, e maior digestibilidade in vitro da matéria seca (DIVMS) do que folhas. Em contrapartida, apresentaram menor digestibilidade in vitro da FDN (DIVFDN), maior teor de lignina na FDN e menor concentração de proteína bruta (PB). Houve redução no teor e digestibilidade da FDN com o avanço da maturidade, enquanto que DIVMS, POL e lignina aumentaram. A DIVMS se mostrou negativamente correlacionada com FDN e FDN/POL, porém não houve correlação entre DIVFDN e FDN ou FDN/POL. Conclui-se que o avanço da maturidade promoveu redução na DIVFDN e aumento na DIVMS, não existindo correlação genética entre acúmulo de açúcar e digestibilidade in vitro da fibra. Os dados deste artigo indicam não ser esperado que a seleção de genótipos com maior DIVFDN do colmo altere o teor de açúcar do mesmo.

Low leaf to fruit ratio delays fruit maturity of ‘Lapins’ sweet cherry on Gisela 5

Canopy leaf to fruit ratio (L:F) of 6-year-old ‘Lapins’ sweet cherry trees on Gisela 5 rootstock was manipulated at the end of stage II (38 DAFB) of fruit development. While control trees showed a L:F ratio of 0.7:1 without alteration, on other trees young fruit were manually removed to yield L:F ratios of 2:1 and 3:1, respectively. All leaves and young fruit on trees were counted 30 DAFB. The effect of altering the source–sink ratio of whole trees on sweet cherry fruit quality parameters (fruit increment, fruit mass, color, total soluble solids content, contents of individual sugars and organic acids) was evaluated in the study. High leaf area to fruit (LA:F) ratios influenced significantly darkest fruit color, higher fruit mass, higher total soluble solids content and higher ratio between sugars and acids, which corresponded to better ripening stage. Contents of glucose, fructose and sorbitol, but not sucrose, sum of individual sugars, and the content of malic acid differed significantly among fruit of the different treatments. Fruit of the most advanced maturity stage (treatment 3:1) had the highest quality. Each day of improved L:F ratio counts towards better sweet cherry fruit quality. The results show that low L:F ratio influenced prolonged ripening process and delayed fruit maturity of ‘Lapins’ sweet cherry.

Anatomia e cinética de degradação do feno de Manihot glaziovii

Anatomy and kinetics of degradation of Manihot glaziovii Hay. This study the structural components of cell wall with its degradability, chemical composition, secondary compounds, in situ degradability, anatomy and tissue degradability of the hay of manicoba (wild cassava) from plants in early fruiting, from savanna vegetation in Ibimirim, Pernambuco. The stem showed cells with varied degrees of lignification, highlighting the presence of gelatinous fibers, lignified pith parenchyma and thick cell walls inside the xylem. The leaves were highlighted by the presence of a girder structure, characterized by the great quantity of mesophyll, constituted by cells with thin walls, contributing to the degradability of dry matter. Idioblasts with druses of oxalate were observed around the vascular tissues, in the midrib. It works like defense mechanisms of plant against herbivores and can affect the availability of minerals for animals. Manicoba hay, in spite of its advanced maturity stage (early fruit development), presents adequate chemical composition and low concentration of cianidric acid and tannins. The mains limits to degradability are cell wall thickness and lignification, particularly in stem tissue. Additionally, several aspects reported here induce to the continuity of studies in several focuses and aim to improve the use this specie as forage.

Anesthetic Effects on the Developing Nervous System

Anesthetic Effects on the Developing Nervous System

1-Methylcyclopropene delays arazá ripening and improves postharvest fruit quality

Six different experiments were conducted to give some practical recommendation to apply 1-MCP during the postharvest handling chain of arazá fruit ( Eugenia stipitata McVaugh). Fruit were harvested in three stages of maturity (mature-green primarily, turning and mature) and treated for 1 to 12 h with 0 (control in air) or 1 μL L −1 1-Methylcyclopropene (1-MCP) at 20 °C. The mature-green fruit were subjected to different storage conditions (7, 10, 12, 13, 20 or 27 °C). The treatment of mature-green fruit with 1-MCP for 1 h, and storage at 12 °C for up to 2 weeks prolonged the shelf-life about one week by delaying or reducing the respiration and ethylene production rates, skin colour changes, the loss of organic acids, and softening, with or without a further shelf-life period of 3 days at 20 °C. At 7 °C, 1-MCP also reduced mature-green fruit weight loss and shrivelling. Extending 1-MCP treatment periods at 20 °C to 6 or 12 h caused partial and uneven ripeness. Treating fruit in their post-climacteric stage of maturity had little effect on ripening compared with the mature-green stage. 1-MCP increased the respiration rate and/or the ethylene production in certain combinations of advanced harvest maturities and/or unfavourable storage temperatures. Recommendations for maintaining postharvest quality are harvesting at the mature-green stage, treatment with 1 μL L −1 of 1-MCP for 1 h, and storage at 12 °C for up to 2 weeks.

Physical Activity and Pregnancy

Regular physical activity is associated with improved physiological, metabolic and psychological parameters, and with reduced risk of morbidity and mortality. Current recommendations aimed at improving the health and well-being of nonpregnant subjects advise that an accumulation of > or =30 minutes of moderate physical activity should occur on most, if not all, days of the week. Regardless of the specific physiological changes induced by pregnancy, which are primarily developed to meet the increased metabolic demands of mother and fetus, pregnant women benefit from regular physical activity the same way as nonpregnant subjects. Changes in submaximal oxygen uptake (VO(2)) during pregnancy depend on the type of exercise performed. During maternal rest or submaximal weight-bearing exercise (e.g. walking, stepping, treadmill exercise), absolute maternal VO(2) is significantly increased compared with the nonpregnant state. The magnitude of change is approximately proportional to maternal weight gain. When pregnant women perform submaximal weight-supported exercise on land (e.g. level cycling), the findings are contradictory. Some studies reported significantly increased absolute VO(2), while many others reported unchanged or only slightly increased absolute VO(2) compared with the nonpregnant state. The latter findings may be explained by the fact that the metabolic demand of cycle exercise is largely independent of the maternal body mass, resulting in no absolute VO(2) alteration. Few studies that directly measured changes in maternal maximal VO(2) (VO(2max)) showed no difference in the absolute VO(2max) between pregnant and nonpregnant subjects in cycling, swimming or weight-bearing exercise. Efficiency of work during exercise appears to be unchanged during pregnancy in non-weight-bearing exercise. During weight-bearing exercise, the work efficiency was shown to be improved in athletic women who continue exercising and those who stop exercising during pregnancy. When adjusted for weight gain, the increased efficiency is maintained throughout the pregnancy, with the improvement being greater in exercising women. Regular physical activity has been proven to result in marked benefits for mother and fetus. Maternal benefits include improved cardiovascular function, limited pregnancy weight gain, decreased musculoskeletal discomfort, reduced incidence of muscle cramps and lower limb oedema, mood stability, attenuation of gestational diabetes mellitus and gestational hypertension. Fetal benefits include decreased fat mass, improved stress tolerance, and advanced neurobehavioural maturation. In addition, few studies that have directly examined the effects of physical activity on labour and delivery indicate that, for women with normal pregnancies, physical activity is accompanied with shorter labour and decreased incidence of operative delivery. However, a substantial proportion of women stop exercising after they discover they are pregnant, and only few begin participating in exercise activities during pregnancy. The adoption or continuation of a sedentary lifestyle during pregnancy may contribute to the development of certain disorders such as hypertension, maternal and childhood obesity, gestational diabetes, dyspnoea, and pre-eclampsia. In view of the global epidemic of sedentary behaviour and obesity-related pathology, prenatal physical activity was shown to be useful for the prevention and treatment of these conditions. Further studies with larger sample sizes are required to confirm the association between physical activity and outcomes of labour and delivery.

Effects of the juvenile hormone analogue methoprene and dietary protein on male melon fly Bactrocera cucurbitae (Diptera: Tephritidae) mating success

The effect of access to dietary protein (P) and the topical application of a juvenile hormone analogue (methoprene (M)) on mating behaviour of male melon fly Bactrocera cucurbitae was assessed in the laboratory and in field cages. Age, dietary protein and methoprene application increased the mating success and influenced the mating behaviour. Treatment with methoprene (M+) to protein-deprived (P−) males had only a modest effect on the acceleration of sexual maturity, but application of methoprene (M+) to protein-fed (P+) males greatly accelerated sexual maturity. Protein diet (P+) increased mating success of males in comparison to protein-deprived (P−) males. Protein and methoprene have a synergistic effect on mating behaviour, since M + P+ treated males exhibit reduced mating latency and achieved higher mating in younger ages than methoprene and/or protein-deprived males. Copulation duration was correlated with nutritional status and M + P+ males copulated longer at the age of advanced sexual maturity than M − P+ males. Our results suggest that in this species with a lek mating system, females discriminate between the males based on their sexual signals, which were influenced by protein in the adult diet, methoprene application and age. The results are discussed in the light of mating competitiveness of precocious treated young males and their relevance to Sterile Insect Technique application against this pest species.

Recapitulation of endochondral bone formation using human adult mesenchymal stem cells as a paradigm for developmental engineering

Mesenchymal stem/stromal cells (MSC) are typically used to generate bone tissue by a process resembling intramembranous ossification, i.e., by direct osteoblastic differentiation. However, most bones develop by endochondral ossification, i.e., via remodeling of hypertrophic cartilaginous templates. To date, endochondral bone formation has not been reproduced using human, clinically compliant cell sources. Here, we aimed at engineering tissues from bone marrow-derived, adult human MSC with an intrinsic capacity to undergo endochondral ossification. By analogy to embryonic limb development, we hypothesized that successful execution of the endochondral program depends on the initial formation of hypertrophic cartilaginous templates. Human MSC, subcutaneously implanted into nude mice at various stages of chondrogenic differentiation, formed bone trabeculae only when they had developed in vitro hypertrophic tissue structures. Advanced maturation in vitro resulted in accelerated formation of larger bony tissues. The underlying morphogenetic process was structurally and molecularly similar to the temporal and spatial progression of limb bone development in embryos. In particular, Indian hedgehog signaling was activated at early stages and required for the in vitro formation of hypertrophic cartilage. Subsequent development of a bony collar in vivo was followed by vascularization, osteoclastic resorption of the cartilage template, and appearance of hematopoietic foci. This study reveals the capacity of human MSC to generate bone tissue via an endochondral program and provides a valid model to study mechanisms governing bone development. Most importantly, this process could generate advanced grafts for bone regeneration by invoking a "developmental engineering" paradigm.