Stem cell behaviors are regulated by multiple microenvironmental cues. As an external signal, mechanical stiffness of the extracellular matrix is capable of governing stem cell fate determination, but how this biophysical cue is translated into intracellular signaling remains elusive. Here, we elucidate mechanisms by which stem cells respond to microenvironmental stiffness through the dynamics of the cytoskeletal network, leading to changes in gene expression via biophysical transduction signaling pathways in two-dimensional culture. Furthermore, a putative rapid shift from original mechanosensing to de novo cell-derived matrix sensing in more physiologically relevant three-dimensional culture is pointed out. A comprehensive understanding of stem cell responses to this stimulus is essential for designing biomaterials that mimic the physiological environment and advancing stem cell-based clinical applications for tissue engineering.

No abstract

No abstract

Stem cells are an attractive cellular source for regenerative medicine and tissue engineering applications due to their multipotency. Although the elasticity of the extracellular matrix (ECM) has been shown to have crucial impacts in directing stem cell differentiation, it is not the only contributing factor. Many researchers have recently attempted to design microenvironments that mimic the stem cell niche with combinations of ECM elasticity and other cues, such as ECM physical properties, soluble biochemical factors and cell-cell interactions, thereby driving cells towards their preferred lineages. Here, we briefly discuss the effect of matrix elasticity on stem cell lineage specification and then summarize recent advances in the study of the combined effects of ECM elasticity and other cues on the differentiation of stem cells, focusing on two aspects: biophysical and biochemical factors. In the future, biomedical scientists will continue investigating the union strength of matrix elasticity and microenvironmental cues for manipulating stem cell fates.

To investigate the HER2 status and clinicopathological features in invasive breast cancer with HER2 ≥4.0 and <6.0, which has always been controversial. Methods: Forty breast cancer cases with HER2 ≥4.0 and <6.0 by fluorescence in situ hybridization (FISH) were collected and classified into two groups based on the HRE2/CEP17 ratio (Group A: ≥2.0, n=22; Group B: <2.0, n=18). Clinicopathological characteristics, HER2 status, risk classification, and molecular typing were further analyzed and compared by 21-Gene expression assay and MammaPrint plus BluePrint test. Results:The majority of cases in both groups were invasive carcinoma (NOS), with histological grade II, HR+, Ki-67 ≥20%, HER2 2+, and a high risk of recurrence, although younger patients and lymph node metastases were more common in Group A. Surprisingly, all HR+ breast cancers in both groups were classified as luminal-type, HR− cases were all basal-type or unknown, and the index of HER2 in all cases was <0.000 using the BluePrint test, which indicated that HER2 status should be negative. Furthermore, the level of HER2 mRNA expression in all cases of both groups was <10.7, which was defined as HER2 negative by the 21-Gene expression assay. In addition, 10 patients of Group A received anti-HER2 neoadjuvant therapy; only one patient with HR-achieved Grade 5 based on the Miller-Payne system, whereas none of the patients achieved pathological complete response (pCR) based on the Residual Cancer Burden system. Conclusion: Group A breast cancer, which has always been unquestionably diagnosed as HER2 amplification, was more likely to be HER2 negative and derived less benefit from anti-HER2 neoadjuvant chemotherapy. Group A breast cancer should be distinguished from classical HER2-positive breast cancers when assessing HER2 FISH, and a larger cohort of Group A patients should be included in further studies.