Secret Life of Tiny Blood Vessels: Lactate, Scaffold and Beyond

Current progress and challenges in the development of brain tissue models: How to grow up the changeable brain in vitro?

“…7. In addition to all above mentioned characteristics, the models aimed to reproduce key events in neurogenesis and neurogenesis-coupled brain plasticity should consider the following additional tasks: 7.1. establishment of multicellular ensembles made of NSCs/NPCs and their progeny as well as fully-differentiated cells (astrocytes, BMECs, CPECs, EpCs), tight integration of functionally and phenotypically distinct compartments (neurogenic niche, NVU/brain parenchyma, and associated brain tissue barriers) on a chip mimicking the regulation of neurogenesis in (patho)physiological conditions 31 , 135 , 281 – 283 ; 7.2. reproduction of ECM composition, oxygen and nutrients supply for better cell viability and functionality, reproduction of metabolic plasticity and local humoral microenvironment supporting cell-to-cell communications, establishment of conditions supportive for neurogenesis and angiogenesis 204 , 284 – 286 ; 7.3. reconstitution of the chip microarchitecture, fluids exchange and establishment of chemical gradients that are supportive for NSCs/NPCs maintenance due to dynamic changes in the concentrations of local and “systemic” regulatory molecules (neurotransmitters, gliotransmitters, growth factors, cytokines, alarmins, metabolites) produced by the cells themselves, infused into the microfluidic device artificially, or embedded into the ECM and scaffolds 13 , 287 ; 7.4. achieving the controllable and reproducible recruitment, proliferation, differentiation, apoptosis of NSCs/NPCs, migration of neuroblasts, maturation of newly-formed neurons and their functional integration within the NVU/brain parenchyma compartment 242 , 244 , 247 , 264 , 288 , 289 ; 7.5. establishment of the molecular machinery responsible for dynamic/phasic changes in the tissue (for instance, circadian/diurnal rhythms and/or mitochondrial dynamics) that are important for determining the stem cells fate or barrier functions 136 , 290 ; 7.6. achievement of prolonged viability of the neurogenic niche in vitro model enabling long-lasting recording of “developmental” and plastic changes in the brain tissue. …”

“…7.3. reconstitution of the chip microarchitecture, fluids exchange and establishment of chemical gradients that are supportive for NSCs/NPCs maintenance due to dynamic changes in the concentrations of local and “systemic” regulatory molecules (neurotransmitters, gliotransmitters, growth factors, cytokines, alarmins, metabolites) produced by the cells themselves, infused into the microfluidic device artificially, or embedded into the ECM and scaffolds 13 , 287 ;…”

Plasticity of Adipose Tissue-Derived Stem Cells and Regulation of Angiogenesis

“…It is well known that hypoxia is associated always with lactate accumulation; therefore, local production of lactate within SVF could regulate differentiation of ASCs into endothelial cells. Indeed, lactate has been shown to serve as a positive regulator of angiogenesis, including model systems with specially designed matrices (lactate-releasing or demonstrating gradients in lactate concentrations) ( Hunt et al, 2007 ; Porporato et al, 2012 ; Malinovskaya et al, 2016 ; Salmin et al, 2017 ), and lactate-enriched microenvironment within clonogenic niches might be able to promote vasculogenesis in the loci of extensive adipogenesis. The proangiogenic activity of lactate often requires IL-8-driven proliferation of endothelial cells ( Polet and Feron, 2013 ), and adipose cells appear to be good producers of IL-8 into the systemic circulation ( Bruun et al, 2004 ).…”