3D Scaffolds to Model the Hematopoietic Stem Cell Niche: Applications and Perspectives.

Hematopoietic stem cells (HSC) are responsible for the production of blood and immune cells during life. HSC fate decisions are dependent on signals from specialized microenvironments in the bone marrow, termed niches. The HSC niche is a tridimensional environment that comprises cellular, chemical, and physical elements. Introductorily, we will revise the current knowledge of some relevant elements of the niche. Despite the importance of the niche in HSC function, most experimental approaches to study human HSCs use bidimensional models. Probably, this contributes to the failure in translating many in vitro findings into a clinical setting. Recreating the complexity of the bone marrow microenvironment in vitro would provide a powerful tool to achieve in vitro production of HSCs for transplantation, develop more effective therapies for hematologic malignancies and provide deeper insight into the HSC niche. We previously demonstrated that an optimized decellularization method can preserve with striking detail the ECM architecture of the bone marrow niche and support HSC culture. We will discuss the potential of this decellularized scaffold as HSC niche model. Besides decellularized scaffolds, several other methods have been reported to mimic some characteristics of the HSC niche. In this review, we will examine these models and their applications, advantages, and limitations.

Impaired expression of CXCL5 and matrix metalloproteinases in the lungs of mice with high susceptibility to Streptococcus pneumoniae infection.

INTRODUCTION: Streptococcus pneumoniae colonizes the nasopharynx of healthy individuals establishing a commensal relationship with the host. In some conditions, bacteria invade the lower respiratory tract and innate immune responses are crucial to avoid diseases such as pneumonia, sepsis, or meningitis. METHODS: Here, we compared the susceptibility to pneumococcal respiratory infection of two outbred mouse lines, AIRmin and AIRmax, selected for low or high acute inflammatory responses, respectively. RESULTS: AIRmin mice showed increased susceptibility to infection with different pneumococcal serotypes, when compared to AIRmax. Significant higher numbers of alveolar macrophages expressing the CD206 mannose receptor were observed in AIRmin mice when compared to AIRmax mice. Despite this difference, secretion of several cytokines and chemokines in the respiratory tract of AIRmin and AIRmax mice, after infection, was similar. The only exception was CXCL5, which was highly induced after pneumococcal infection in AIRmax mice but not in AIRmin mice. Reduced expression of the matrix metalloproteinases (MMP) 2, 3, 8, and 9, as well as reduced activities of MMPs were also observed in the lungs of AIRmin mice, after infection. Such impaired responses may have contributed to the low influx of neutrophils observed in the airways of these mice. Finally, high percentages of macrophages and neutrophils in apoptosis or necrosis, at the site of infection, were also observed in AIRmin mice, suggesting that leukocyte functionality is also compromised. CONCLUSIONS: Our results indicate that CXCL5 and MMPs contribute to the resistance to pneumococcal infection in mice.