Mesenchymal stem cells (MSCs) exhibit tropism for sites of tissue injury and tumors. However, the influence of the microenvironment on MSC phenotype and localization remains incompletely characterized. In this study, we begin to define a macrophage-induced MSC phenotype. These MSCs secrete interleukin-6 (IL-6), CCL5, and interferon gamma-induced protein-10 (CXCL10) and exhibit increased mobility in response to multiple soluble factors produced by macrophages including IL-8, CCL2, and CCL5. The pro-migratory phenotype is dependent on activation of a c-Jun N-terminal kinase (JNK) pathway. This work begins to identify the influence of macrophages on MSC biology. These interactions are likely to play an important role in the tissue inflammatory response and may provide insight into the migratory potential of MSCs in inflammation and tissue injury.
The intervertebral disc (IVD) exhibits
complex structure and biomechanical
function, which supports the weight of the body and permits motion.
Surgical treatments for IVD degeneration (e.g., lumbar fusion, disc
replacement) often disrupt the mechanical environment of the spine
which lead to adjacent segment disease. Alternatively, disc tissue
engineering strategies, where cell-seeded hydrogels or fibrous biomaterials
are cultured in vitro to promote matrix deposition,
do not recapitulate the complex IVD mechanical properties. In this
study, we use 3D printing of flexible polylactic acid (FPLA) to fabricate
a viscoelastic scaffold with tunable biomimetic mechanics for whole
spine motion segment applications. We optimized the mechanical properties
of the scaffolds for equilibrium and dynamic moduli in compression
and tension by varying fiber spacing or porosity, generating scaffolds
with de novo mechanical properties within the physiological
range of spine motion segments. The biodegradation analysis of the
3D printed scaffolds showed that FPLA exhibits lower degradation rate
and thus has longer mechanical stability than standard PLA. FPLA scaffolds
were biocompatible, supporting viability of nucleus pulposus (NP)
cells in 2D and in FPLA+hydrogel composites. Composite scaffolds cultured
with NP cells maintained baseline physiological mechanical properties
and promoted matrix deposition up to 8 weeks in culture. Mesenchymal
stromal cells (MSCs) cultured on FPLA adhered to the scaffold and
exhibited fibrocartilaginous differentiation. These results demonstrate
for the first time that 3D printed FPLA scaffolds have de
novo viscoelastic mechanical properties that match the native
IVD motion segment in both tension and compression and have the potential
to be used as a mechanically stable and biocompatible biomaterial
for engineered disc replacement.
Increasing evidence shows that the interaction between neoplastic cells and the surrounding stroma is a critical factor in solid tumor growth. The tumor stroma is made up of diverse cellular populations including macrophages, lymphocytes, vascular cells, and carcinoma-associated fibroblasts. The complex interactions between the stroma and neoplastic cells are largely unexplored. Initial therapies aimed at disrupting angiogenesis within the tumor microenvironment have met with success in a number of tumor types. An improved understanding of stromal signaling pathways is likely to identify additional novel therapeutic targets.
The prevalence of obesity continues to increase at an alarming rate, and, thus far, advances in medical management have been relatively ineffective in slowing this trend. Lifestyle modifications such as diet and exercise are effective initially, but most patients regain the weight in the long term. Bariatric surgery is the most effective strategy for achieving long-term weight loss; however, as with all surgical procedures, it has potential complications.
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