Synergistic growth factor microenvironments

Growth factors (GF) are remarkably powerful signalling molecules that orchestrate developmental biology. GFs are currently used in medjcal applications with limited success but it is clear that if their potential can be harnessed for biomedicine then they could underpin the discipline of regenerative medicine. However, while we understand that biology uses cell-secreted growth factors tethered to the ECM, biologists typically employ GFs in soluble format at high concentrations. When used in vivo, this causes off-target, unwanted effects, which severely limits their use. There is a vast amount of literature dealing with material systems that control the delivery of GFs. However, it was soon observed that GFs could be more effectively presented bound to surfaces from a solid-phase state rather than in soluble form, recapitulating the way the extracellular matrix (ECM) binds GFs. In parallel, evidence was found that within the ECM, GFs can actually work in cooperation with integrins and that this produced ehnaced GF signalling due to the crosstalk between both receptors. Recently this knowledge was used to engineer microenvironments that target simultaneous integrin and GF receptor engagement seeking to maximise GF effects in vitro (e.g. in terms of stem cell differentiation) but also tissue repair in vivo (e.g. bone regeneration and wound healing). This feature article introduces the concept of synergistic GF/integrin signalling and then introduces GF delivery systems that were key in the development of more advanced synergistic growth factor microenvironments

Growth factor in f(T) gravity

We derive the evolution equation of growth factor for the matter over-dense perturbation in $f(T)$ gravity. For instance, we investigate its behavior in power law model at small redshift and compare it to the prediction of $\Lambda$CDM and dark energy with the same equation of state in the framework of Einstein general relativity. We find that the perturbation in $f(T)$ gravity grows slower than that in Einstein general relativity if \p f/\p T>0 due to the effectively weakened gravity.Comment: 15 pages,1 figure; v2,typos corrected; v3, discussions added, accepted by JCA

Effect on the canine Eck fistula liver of intraportal TGF‐β alone or with hepatic growth factors

Transforming growth factor‐β canceled the hepatocyte proliferation caused by transforming growth factor‐α when the two substances were mixed and administered through a disconnected central portal vein branch after creation of an Eck fistula. In contrast, transforming growth factor‐β had no antidotal action on the stimulatory effects of insulin or full test doses of insulinlike factor‐2, hepatocyte growth factor, epidermal growth factor or triiodothymanine. A minor antidotal effect on hepatic stimulatory substance activity could be detected, but only with hepatic stimulatory substance was given in doses smaller than those known to cause maximum stimulatory response. These results suggest a highly specific pharmacological and physiological interaction between transforming growth factor‐α and transforming growth factor‐α in the modulation of liver growth control. (HEPATOLOGY 1992;16:1267–1270.) Copyright © 1992 American Association for the Study of Liver Disease

An acidic fibroblast growth factor protein generated by alternate splicing acts like an antagonist.

Polymerase chain reaction amplification of cDNA for acidic fibroblast growth factor in several lines of cultured human cells revealed two forms of mRNA. The novel smaller mRNA lacks the entire second coding exon of the acidic fibroblast growth factor gene, whereas the previously identified mRNA consists of three coding exons. The truncated variant of acidic fibroblast growth factor (aFGF') is only 60 amino acids long with an apparent molecular mass of 6.7 kD on sodium dodecyl sulfate gels in contrast to 18 kD for the full-length acidic fibroblast growth factor. aFGF' elicits only minimal fibroblast proliferation and antagonizes the effects of acidic fibroblast growth factor when added exogenously to or when coexpressed with aFGF in BALB/c/3T3 fibroblasts. Thus, the truncated variant of acidic fibroblast growth factor may provide fibroblasts with a unique mechanism for endogenous regulation of their responses to acidic fibroblast growth factor