Bone Marrow Stromal Cells Promotes Morphological Senescence of Prostate Cancer Cells and Inhibits Metastasis Associated 1 Gene Level

This study assessed the mechanism of Bone Marrow Stromal Cells (BMSCs) in prostate cancer (PC) and its effect on MTA-1 gene and PC cell senescence. PC-3 cells were assigned into QL group (prostate cancer group: normal culture) and GS group (BMSCs group: treated with BMSCs) followed by analysis of MTA-1 level, cell senescence, apoptosis and invasion. MTA-1 level in QL group (0.83±0.07) was significantly higher than GS group (0.14±0.02) (P < 0.05), indicating that BMSCs had an inhibitory effect on MTA-1 expression. Similar change of MTA-l mRNA was also found with higher level in QL group than GS group (P < 0.05). Cell senescence was found in QS group but not QL group, indicating that BMSCs promote cell senescence. Compared with GS group, QL group has a higher cell number in G0/G1 (67.13±6.45%) and S (19.59±3.35%) than GS group (G0/G1:50.51±2.19% and S: 11.42±1.61%) but lower G2/M (QL: 15.97±3.59% versus GS: 32.25±3.24%). QL group had significantly lower cell apoptosis rate at 35 h (5.21±1.2%) and 45 h (3.97±0.95%) than GS group at 35 h (17.85±1.23%), 45 h (10.21±1.26%) with elevated number of invasions. In conclusion, BMSCs promote PC-3 cell senescence and apoptosis by inhibiting the expression of MTA-1 and reduce cell invasion ability.

Heparin Enriched-WPI Coating on Ti6Al4V Increases Hydrophilicity and Improves Proliferation and Differentiation of Human Bone Marrow Stromal Cells

Titanium alloy (Ti6Al4V) is one of the most prominent biomaterials for bone contact because of its ability to bear mechanical loading and resist corrosion. The success of Ti6Al4V implants depends on bone formation on the implant surface. Hence, implant coatings which promote adhesion, proliferation and differentiation of bone-forming cells are desirable. One coating strategy is by adsorption of biomacromolecules. In this study, Ti6Al4V substrates produced by additive manufacturing (AM) were coated with whey protein isolate (WPI) fibrils, obtained at pH 2, and heparin or tinzaparin (a low molecular weight heparin LMWH) in order to improve the proliferation and differentiation of bone-forming cells. WPI fibrils proved to be an excellent support for the growth of human bone marrow stromal cells (hBMSC). Indeed, WPI fibrils were resistant to sterilization and were stable during storage. This WPI-heparin-enriched coating, especially the LMWH, enhanced the differentiation of hBMSC by increasing tissue non-specific alkaline phosphatase (TNAP) activity. Finally, the coating increased the hydrophilicity of the material. The results confirmed that WPI fibrils are an excellent biomaterial which can be used for biomedical coatings, as they are easily modifiable and resistant to heat treatments. Indeed, the already known positive effect on osteogenic integration of WPI-only coated substrates has been further enhanced by a simple adsorption procedure.

Recent Advances in Translational Adipose-Derived Stem Cell Biology

Multipotent mesenchymal stem cells/marrow stromal cells (MSCs), originally discovered in the bone marrow by Alexander Friedenstein as early as 1968 [...]

Effects of Bone Marrow Stromal Cells (BMSCs) on Behavior, Infarct Size and HIF-1α Expression in Stroke Rats

This study aims to assess BMSCs’ effect on the behavior, infarct size and HIF-1α expression in stroke rats. Rats were separated into sham group, CVA group and BMSCs group with 10 rats in each group followed by analysis of neuroethology scores, brain tissue pathology and infarct size, and HIF-1α level in brain tissues. No difference of neurological scores was found between CVA group and BMSCs group after 3 hours (P > 0.05). After BMSCs transplantation, the nerve score was significantly reduced (P < 0.05) and cognitive function was significantly improved compared to CVA group. Compared with sham rats, CAV rats had a larger area of infarction and the infarcted tissue cells showed degeneration or necrosis with reduced cell number and obvious edema, which were all improved in BMSCs group. CVA group showed a larger area of infarct tissue (P < 0.05), which was reduced in BMSCs group (P < 0.05). Compared with sham group, CVA group showed significantly upregulated HIF-1α level (P < 0.05) which was reduced in BMSCs group (P < 0.05). BMSCs has a certain repair effect on the ethology of stroke rats possibly via inhibition of HIF-1α level in cerebral infarction and brain tissue.

Bone-Forming Peptide-4 Induces Osteogenic Differentiation and VEGF Expression on Multipotent Bone Marrow Stromal Cells

Bone morphogenetic proteins (BMPs) have been widely used as treatment for bone repair. However, clinical trials on fracture repair have challenged the effectiveness of BMPs and suggested that delivery of multipotent bone marrow stromal cells (BMSCs) might be beneficial. During bone remodeling and bone fracture repair, multipotent BMSCs differentiate into osteoblasts or chondrocytes to stimulate bone formation and regeneration. Stem cell-based therapies provide a promising approach for bone formation. Extensive research has attempted to develop adjuvants as specific stimulators of bone formation for therapeutic use in patients with bone resorption. We previously reported for the first time bone-forming peptides (BFPs) that induce osteogenesis and bone formation. BFPs are also a promising osteogenic factor for prompting bone regeneration and formation. Thus, the aim of the present study was to investigate the underlying mechanism of a new BFP-4 (FFKATEVHFRSIRST) in osteogenic differentiation and bone formation. This study reports that BFP-4 induces stronger osteogenic differentiation of BMSCs than BMP-7. BFP-4 also induces ALP activity, calcium concentration, and osteogenic factors (Runx2 and osteocalcin) in a dose dependent manner in BMSCs. Therefore, these results indicate that BFP-4 can induce osteogenic differentiation and bone formation. Thus, treatment of multipotent BMSCs with BFP-4 enhanced osteoblastic differentiation and displayed greater bone-forming ability than BMP-7 treatment. These results suggest that BFP-4-stimulated cell therapy may be an efficient and cost-effective complement to BMP-7-based clinical therapy for bone regeneration and formation.

Untargeted metabolomics in primary murine bone marrow stromal cells reveals distinct profile throughout osteoblast differentiation

Introduction Skeletal homeostasis is an exquisitely regulated process most directly influenced by bone resorbing osteoclasts, bone forming osteoblasts, and the mechano-sensing osteocytes. These cells work together to constantly remodel bone as a mechanism to prevent from skeletal fragility. As such, when an individual experiences a disconnect in these tightly coupled processes, fracture incidence increases, such as during ageing, gonadal hormone deficiency, weightlessness, and diabetes. While therapeutic options have significantly aided in the treatment of low bone mineral density (BMD) or osteoporosis, limited options remain for anabolic or bone forming agents. Therefore, it is of interest to continue to understand how osteoblasts regulate their metabolism to support the energy expensive process of bone formation. Objective The current project sought to rigorously characterize the distinct metabolic processes and intracellular metabolite profiles in stromal cells throughout osteoblast differentiation using untargeted metabolomics. Methods Primary, murine bone marrow stromal cells (BMSCs) were characterized throughout osteoblast differentiation using standard staining protocols, Seahorse XFe metabolic flux analyses, and untargeted metabolomics. Results We demonstrate here that the metabolic footprint of stromal cells undergoing osteoblast differentiation are distinct, and while oxidative phosphorylation drives adenosine triphosphate (ATP) generation early in the differentiation process, mature osteoblasts depend on glycolysis. Importantly, the intracellular metabolite profile supports these findings while also suggesting additional pathways critical for proper osteoblast function. Conclusion These data are the first of their kind to characterize these metabolites in conjunction with the bioenergetic profile in primary, murine stromal cells throughout osteoblast differentiation and provide provocative targets for future investigation.

Molecular Indicators of Biomaterials Osteoinductivity - Cell Migration, BMP Production and Signalling Turns a Key

In this work we dissect the osteoinductive properties of selected bioactive materials obtained in a 3D form, and based on PLGA matrix and 2 types of gel-derived bioactive glasses (SBGs) of SiO2-CaO system, each with and without P2O5. The study is designed to avoid any osteogenic stimuli beyond the putative osteogenic bioactive glass compound of the studied materials. Previously we found that, when used as growth surfaces (i.e. material sheets), some of these materials were capable to support osteogenesis of bone marrow stromal cells (BMSC) without the need for any additional osteogenic cell treatment. In this work we explore further the role of BMP production and signaling upon BMSC culture on selected, SBG/PLGA 3D scaffolds as well as BMSC migration toward the condition media obtained from such cell-loaded materials. Our results show that BMP signaling of osteoprogenitor cells as well as their migration rate may present important indicators of materials osteoinductivity.

Myeloma–Bone Interaction: A Vicious Cycle via TAK1–PIM2 Signaling

Multiple myeloma (MM) has a propensity to develop preferentially in bone and form bone-destructive lesions. MM cells enhance osteoclastogenesis and bone resorption through activation of the RANKL–NF-κB signaling pathway while suppressing bone formation by inhibiting osteoblastogenesis from bone marrow stromal cells (BMSCs) by factors elaborated in the bone marrow and bone in MM, including the soluble Wnt inhibitors DKK-1 and sclerostin, activin A, and TGF-β, resulting in systemic bone destruction with loss of bone. Osteocytes have been drawn attention as multifunctional regulators in bone metabolism. MM cells induce apoptosis in osteocytes to trigger the production of factors, including RANKL, sclerostin, and DKK-1, to further exacerbate bone destruction. Bone lesions developed in MM, in turn, provide microenvironments suited for MM cell growth/survival, including niches to foster MM cells and their precursors. Thus, MM cells alter the microenvironments through bone destruction in the bone where they reside, which in turn potentiates tumor growth and survival, thereby generating a vicious loop between tumor progression and bone destruction. The serine/threonine kinases PIM2 and TAK1, an upstream mediator of PIM2, are overexpressed in bone marrow stromal cells and osteoclasts as well in MM cells in bone lesions. Upregulation of the TAK1–PIM2 pathway plays a critical role in tumor expansion and bone destruction, posing the TAK1–PIM2 pathway as a pivotal therapeutic target in MM.