Purpose Articular chondroprogenitors, a suitable contender for cell-based therapy in cartilage repair, routinely employ fetal bovine serum (FBS) for expansion and differentiation. The possibility of transplant rejections or zoonoses transmissions raise a need for xeno-free alternatives. Use of human platelet lysate (hPL), a nutrient supplement abundant in growth factors, has not been reported for human chondroprogenitor expansion thus far. Our aim was to compare the biological profile of chondroprogenitors grown in hPL versus FBS. Methods Chondroprogenitors were isolated from 3 osteoarthritic knee joints. Following differential fibronectin adhesion assay, passage 0 cells grown in (a) 10% FBS and (b) 10% hPL were considered for assessment of growth kinetics, surface marker expression, gene expression, and trilineage differentiation. Latent transforming growth factor–β1 (TGFβ1) levels were also measured for each culture medium used. Results Cellular proliferation was significantly higher in cells grown with hPL ( P < 0.01). Surface marker expression was comparable except in CD-146 where hPL group had significantly higher values ( P = 0.03). Comparison of mRNA expression revealed notably low values of collagen I, collagen X, aggrecan, and collagen II ( P < 0.05). Trilineage differentiation was seen in both groups with higher alizarin red uptake noted in hPL. There were also significantly higher levels of latent TGFβ1 in the medium containing hPL as compared to FBS. Conclusions This is the first in vitro xeno-free study to affirm that hPL can serve as an optimal growth supplement for expansion of articular chondroprogenitors, although an in-depth assessment of resident growth factors and evaluation of different dilutions of hPL is required to assess suitability for use in translational research.
This study presents electrical modelling of the arterial system to understand the effect of adrenaline on the aortae and small arteries in terms of their resistance and compliance. There is no categorical documentation in the current literature on the precise locations of arterial resistance (R) and compliance (C) in vasculature. Knowledge of their exact locations in the arterial tree enables re-assessment of the differential action of vasoactive drugs on resistance versus compliance vessels once we resolve beat-tobeat changes in R and C in response to these drugs. Isolated goat aortae and small arteries were perfused with a pulsatile pump and lumen pressures were recorded before and after addition of adrenaline. Equivalent electrical models were simulated, and biological data was compared against the electrical equivalents to derive interpretations. In the aortae, systolic pressure increased, diastolic pressure decreased, pulse pressure increased (P = .018); but the mean pressure remained the same (P = .357).Whereas in small artery, vasoconstriction caused an increase in systolic, diastolic, and mean pressures (P = .028). Simulations allow us to infer that vasoconstriction in the aorta leads to a reduction in compliance, but an increase in resistance if any, is not sufficient to alter the mean aortic pressure. Whereas vasoconstriction in small arteries increases resistance, but a decrease in compliance, if any, does not affect any of the pressure parameters measured. The presented study is first of its kind to give experimental evidence that large arteries and aorta are the only compliance vessels and small arteries are the only resistance vessels.
Vasoconstriction in small arteries and arterioles is known to increase resistance to flow, while vasoconstriction in large arteries and aorta is known to decrease their compliance. Besides this general understanding, there is no systematic documentation on what happens to small artery compliance and large artery resistance during vasoconstriction and the corresponding alterations in vascular pressure. The aim of the study is to assess the effect of adrenaline on goat aortae and small arteries in terms of resistance and compliance.Isolated goat aortae and small arteries were perfused with a pulsatile pump and lumen pressure was recorded before and after addition of adrenaline. In the aortae, systolic pressure increased, diastolic pressure decreased, pulse pressure increased (p = 0.018, WSR); but the mean pressure remained the same (p = 0.357, WSR). Small artery vasoconstriction caused an increase in systolic, diastolic and mean pressures (p = 0.028, WSR). Using length, radius, and thickness data from the tissues and the tubes of the experimental set-up, electrical models were simulated to understand the biological data. The simulations allow us to infer that vasoconstriction in aorta leads to a reduction in compliance, but an increase in resistance if any, is not sufficient to change the mean aortic pressure. On the other hand, vasoconstriction in small arteries increases resistance, but a decrease in compliance if any, does not affect any of the four pressure parameters measured. Vasoconstriction in aorta decreases compliance and therefore increases pulse pressure but does not change resistance significantly enough to alter mean pressure.Key Points SummaryThe main aim of the study is to understand where exactly resistance (R) and compliance (C) components of the vasculature occur. There is no definitive evidence for the effect of large artery vasoconstriction on resistance and hence the mean arterial pressure.The manuscript presents biological experiments studying the pressure response of goat aorta and small arteries to adrenaline (invitro) and the interpretations using equivalent electrical models.The study shows that in aorta and large arteries, vasoconstriction does not lead to a reduction in lumen diameter sufficient to cause a rise in resistance and mean pressure as compared to small arteries.Knowledge of exact location of R and C in the arterial tree enables re-assessment of the differential action of vasoactive drugs on resistance versus compliance vessels once we resolve beat-to-beat R and C changes in response to a drug. This way antihypertensive therapy can be tailored to address the specific cause of the type of hypertension.
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