Engineered Tools to Study Intercellular Communication

Yang, Benjamin; Westerhof, Trisha M.; Sabin, Kaitlyn; Merajver, Sofía D.; Aguilar, Carlos A.

doi:10.1002/advs.202002825

Cited by 53 publications

(44 citation statements)

References 191 publications

(217 reference statements)

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“…Thus, Schwann cells and glia may shift in phenotype through aging 56 or after persistent denervation from secretion of neurotrophic factors that positively signal to motor neurons and MuSCs 57 to a phenotype that inhibits fusion of MuSCs through secretion of TGF- and S100. While we cannot exclude that additional factors 58 and other cell types may also contribute to this process, our results suggest reductions in MuSC number and attenuation of MuSC ability to fuse in aged muscle may contribute to lack of reinnervation and degenerative changes that occur at the muscle endplate 59,60 . Degeneration of the NMJ has been shown to be a gradual process 61 , resulting from imbalances between denervation and new innervation.…”

Section: Discussionmentioning

confidence: 92%

Murine muscle stem cell response to perturbations of the neuromuscular junction are attenuated with aging

Larouche

Mohiuddin

Choi

et al. 2021

eLife

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During aging and neuromuscular diseases, there is a progressive loss of skeletal muscle volume and function impacting mobility and quality of life. Muscle loss is often associated with denervation and a loss of resident muscle stem cells (satellite cells or MuSCs), however, the relationship between MuSCs and innervation has not been established. Herein, we administered severe neuromuscular trauma to a transgenic murine model that permits MuSC lineage tracing. We show that a subset of MuSCs specifically engraft in a position proximal to the neuromuscular junction (NMJ), the synapse between myofibers and motor neurons, in healthy young adult muscles. In aging and in a mouse model of neuromuscular degeneration (Cu/Zn superoxide dismutase knockout – Sod1-/-), this localized engraftment behavior was reduced. Genetic rescue of motor neurons in Sod1-/- mice reestablished integrity of the NMJ in a manner akin to young muscle and partially restored MuSC ability to engraft into positions proximal to the NMJ. Using single cell RNA-sequencing of MuSCs isolated from aged muscle, we demonstrate that a subset of MuSCs are molecularly distinguishable from MuSCs responding to myofiber injury and share similarity to synaptic myonuclei. Collectively, these data reveal unique features of MuSCs that respond to synaptic perturbations caused by aging and other stressors.

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Section: Discussionmentioning

confidence: 92%

Murine muscle stem cell response to perturbations of the neuromuscular junction are attenuated with aging

Larouche

Mohiuddin

Choi

et al. 2021

eLife

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“…These results enlighten the efficiency of these platforms as potential cellular containers, allowing continuous diffusion of essential molecules for cell proliferation, making possible the intercommunication with the native tissue, creating an adequate semi-closed environment to coordinate physiological functions such as proper differentiation. [29] The presence of catechol-like molecules in the gelatin side chains opens the possibility to explore its adhesive properties onto several surfaces (organic and inorganic). [30,31] To perceive the potential of these macrocapsules in adherence to tissues or to construct 3D structures, we conducted easy-made studies (Figure 2C).…”

Section: Characterization Of the Morphology And Adhesion Profile Of The Liquefied Capsulesmentioning

confidence: 99%

Design of Protein‐Based Liquefied Cell‐Laden Capsules with Bioinspired Adhesion for Tissue Engineering

Gomes

Costa

Oliveira

et al. 2021

Adv Healthcare Materials

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Platforms with liquid cores are extensively explored as cell delivery vehicles for cell-based therapies and tissue engineering. However, the recurrence of synthetic materials can impair its translation into the clinic. Inspired by the adhesive proteins secreted by mussels, liquefied capsule is developed using gelatin modified with hydroxypyridinones (Gel-HOPO), a catechol analogue with oxidant-resistant properties. The protein-based liquefied macrocapsule permitted the compartmentalization of living cells by an approachable and non-time-consuming methodology resorting to i) superhydrophobic surfaces as a processing platform of hydrogel beads, ii) gelation of gelatin at temperatures < 25°C, iii) iron coordination of the hydroxypyridinone (HOPO) moieties at physiological pH, and iv) core liquefaction at 37°C. With the design of a proteolytically degradable shell, the possibility of encapsulating human adipose-derived mesenchymal stem cells (hASC) with and without the presence of polycaprolactone microparticles ( PCL) is evaluated. Showing prevalence toward adhesion to the inner shell wall, hASC formed a monolayer evidencing the biocompatibility and adequate mechanical properties of these platforms for proliferation, diminishing the need for PCL as a supporting substrate. This new protein-based liquefied platform can provide biofactories devices of both fundamental and practical importance for tissue engineering and regenerative medicine or in other biotechnology fields.

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“…Notably, improved drug sensitivity can be obtained using microfluidic 3D systems compared to static culture systems. With the utilization of further engineering approaches to control the initial cellular composition, shape, and size of cell aggregates; cell-cell and cell-ECM[ 54 ] interactions; and biochemical gradients similar to in vivo microenvironment, the incoming generation of organoids-on-a-chip has considerable potential for large-scale applications in high-throughput drug testing and screening.…”

Section: Advances and Limitations In Modeling Hepatitis B Infectionmentioning

confidence: 99%

Hepatitis B virus infection modeling using multi-cellular organoids derived from human induced pluripotent stem cells

Cao¹,

Ge²,

Wang³

et al. 2021

WJG

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Chronic infection with hepatitis B virus (HBV) remains a global health concern despite the availability of vaccines. To date, the development of effective treatments has been severely hampered by the lack of reliable, reproducible, and scalable in vitro modeling systems that precisely recapitulate the virus life cycle and represent virus-host interactions. With the progressive understanding of liver organogenesis mechanisms, the development of human induced pluripotent stem cell (iPSC)-derived hepatic sources and stromal cellular compositions provides novel strategies for personalized modeling and treatment of liver disease. Further, advancements in three-dimensional culture of self-organized liver-like organoids considerably promote in vitro modeling of intact human liver tissue, in terms of both hepatic function and other physiological characteristics. Combined with our experiences in the investigation of HBV infections using liver organoids, we have summarized the advances in modeling reported thus far and discussed the limitations and ongoing challenges in the application of liver organoids, particularly those with multi-cellular components derived from human iPSCs. This review provides general guidelines for establishing clinical-grade iPSC-derived multi-cellular organoids in modeling personalized hepatitis virus infection and other liver diseases, as well as drug testing and transplantation therapy.

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Engineered Tools to Study Intercellular Communication

Cited by 53 publications

References 191 publications

Murine muscle stem cell response to perturbations of the neuromuscular junction are attenuated with aging

Murine muscle stem cell response to perturbations of the neuromuscular junction are attenuated with aging

Design of Protein‐Based Liquefied Cell‐Laden Capsules with Bioinspired Adhesion for Tissue Engineering

Hepatitis B virus infection modeling using multi-cellular organoids derived from human induced pluripotent stem cells

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