Encapsulated oligodendrocyte precursor cell fate is dependent on PDGF‐AA release kinetics in a 3D microparticle‐hydrogel drug delivery system

Demyelinating injuries and diseases, like multiple sclerosis, affect millions of people worldwide.Oligodendrocyte precursor cells (OPCs) have the potential to repair demyelinated tissue because they can both self-renew and differentiate into oligodendrocytes (OLs), the myelin producing cells of the central nervous system (CNS). Cell-matrix interactions impact OPC differentiation into OLs, but the process is not fully understood. Biomaterial hydrogel systems help to elucidate cellmatrix interactions because they can mimic specific properties of native CNS tissue in an in vitro setting. We investigated whether OPC maturation into OLs is influenced by interacting with a urokinase plasminogen activator (uPA) degradable extracellular matrix (ECM). uPA is a proteolytic enzyme that is transiently upregulated in the developing rat brain, with peak uPA expression correlating with an increase in myelin production in vivo. OPC-like cells isolated through the Mosaic Analysis with Double Marker technique (MADM OPCs) produced low molecular weight uPA in culture. MADM OPCs were encapsulated into two otherwise similar elastin-like protein (ELP) hydrogel systems: one that was uPA degradable and one that was nondegradable. Encapsulated MADM OPCs had similar viability, proliferation, and metabolic activity in uPA degradable and non-degradable ELP hydrogels. Expression of OPC maturation-associated genes, however, indicated that uPA degradable ELP hydrogels promoted MADM OPC maturation although not sufficiently for these cells to differentiate into OLs.

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“…Custom primers were used for gene amplification (Table 2, Bio-Rad). 37,38 2.14. Statistical Analysis.…”

Section: Experimental Methodsmentioning

confidence: 99%

Guiding Oligodendrocyte Precursor Cell Maturation With Urokinase Plasminogen Activator-Degradable Elastin-like Protein Hydrogels

et al. 2020

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“…Given the abundance of intracellular cancer-related miRNAs in different cancer types, these structures pose enormous potential in accurate and sensitive differentiation of cancer cells. In order to study the delivery of soluble molecules to target cells in their native environment, in vitro systems that utilize hydrogels with tunable chemical, physical, and mechanical properties that match native tissues can be used to determine cellular response [87]. In order to probe the nuanced relationship between the delivery of platelet derived growth factor-AA (PDGF-AA) and oligodendrocyte precursor cell (OPC) fate, a PEG-based hydrogel with encapsulated PLGA microparticles containing (PDGF-AA) was used to simulate seven different release schemes and study the effect of each on OPCs cultured in the hybrid hydrogel [87].…”

Section: Biomedical Applications Of Hybrid Hydrogelsmentioning

confidence: 99%

“…In order to study the delivery of soluble molecules to target cells in their native environment, in vitro systems that utilize hydrogels with tunable chemical, physical, and mechanical properties that match native tissues can be used to determine cellular response [87]. In order to probe the nuanced relationship between the delivery of platelet derived growth factor-AA (PDGF-AA) and oligodendrocyte precursor cell (OPC) fate, a PEG-based hydrogel with encapsulated PLGA microparticles containing (PDGF-AA) was used to simulate seven different release schemes and study the effect of each on OPCs cultured in the hybrid hydrogel [87]. The results of these experiments support the hypothesis that burst release followed by withdrawal of PDGF-AA results in survival, proliferation, and differentiation of OCPs in the hybrid hydrogel and that OPC fate is dependent on release kinetics, rather than the amount of PDGF-AA delivered [87].…”

Section: Biomedical Applications Of Hybrid Hydrogelsmentioning

confidence: 99%

“…In order to probe the nuanced relationship between the delivery of platelet derived growth factor-AA (PDGF-AA) and oligodendrocyte precursor cell (OPC) fate, a PEG-based hydrogel with encapsulated PLGA microparticles containing (PDGF-AA) was used to simulate seven different release schemes and study the effect of each on OPCs cultured in the hybrid hydrogel [87]. The results of these experiments support the hypothesis that burst release followed by withdrawal of PDGF-AA results in survival, proliferation, and differentiation of OCPs in the hybrid hydrogel and that OPC fate is dependent on release kinetics, rather than the amount of PDGF-AA delivered [87]. Table 3 summarizes studies involving a range of potential medical applications of hybrid hydrogels; these materials could also be used to as in vitro models of physiological microenvironments for applications such as drug screening [84,85].…”

Section: Biomedical Applications Of Hybrid Hydrogelsmentioning

confidence: 99%

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Hybrid hydrogels for biomedical applications

Palmese

Thapa

Sullivan

et al. 2019

Current Opinion in Chemical Engineering

147

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The use of hydrogels in biomedical applications dates back multiple decades, and the engineering potential of these materials continues to grow with discoveries in chemistry and biology. The approaches have led to increasing complex hydrogels that incorporate both synthetic and natural polymers and functional domains for tunable release kinetics, mediated cell response, and ultimately use in clinical and research applications in biomedical practice. This review focuses on recent advances in hybrid hydrogels that incorporate nano/microstructures, their synthesis, and applications in biomedical research. Examples discussed include the implementation of click reactions, photopatterning, and 3D printing for the facile production of these hybrid hydrogels, the use of biological molecules and motifs to promote a desired cellular outcome, and the tailoring of kinetic and transport behavior through hybrid-hydrogel engineering to achieve desired biomedical outcomes. Recent progress in the field has established promising approaches for the development of biologically relevant hybrid hydrogel materials with potential applications in drug discovery, drug/gene delivery, and regenerative medicine.

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“…Moreover, the kinetics of drug release from hydrogel microcarriers can be tailored by adjusting properties of the carrier, such as monomers utilized, crosslinking density, use of a coating (to create a core-shell structure), as well as several other parameters. An example of this is the recently developed hydrogel microparticle drug delivery system comprised of poly(lactic-co-glycolic) acid (synthesized via a water-in-oil emulsion) for the release of platelet derived growth factor-AA (Pinezich et al 2018). This specific growth factor has been studied as a signaling molecule to initiate a response in oligodendrocyte precursor cells, which can lead to proliferation or differentiation of central nervous system tissue after injury or disease.…”

Section: Microscale Hydrogels For Drug Deliverymentioning

confidence: 99%

Engineered microscale hydrogels for drug delivery, cell therapy, and sequencing

Wechsler

Stephenson

Murphy

et al. 2019

Biomed Microdevices

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Engineered microscale hydrogels have emerged as promising therapeutic approaches for the treatment of various diseases. These microgels find wide application in the biomedical field because of the ease of injectability, controlled release of therapeutics, flexible means of synthesis, associated tunability, and can be engineered as stimuli-responsive. While bulk hydrogels of several length-scale dimensions have been used for over two decades in drug delivery applications, their use as microscale carriers of drug and cell-based therapies is relatively new. Herein, we critically summarize the fundamentals of hydrogels based on their equilibrium and dynamics of their molecular structure, as well as solute diffusion as it relates to drug delivery. In addition, examples of common microgel synthesis techniques are provided. The ability to tune microscale hydrogels to obtain controlled release of therapeutics is discussed, along with microgel considerations for cell encapsulation as it relates to the development of cell-based therapies. We conclude with an outlook on the use of microgels for cell sequencing, and the convergence of the use of microscale hydrogels for drug delivery, cell therapy, and cell sequencing based systems.

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Encapsulated oligodendrocyte precursor cell fate is dependent on PDGF‐AA release kinetics in a 3D microparticle‐hydrogel drug delivery system

Cited by 10 publications

References 51 publications

Guiding Oligodendrocyte Precursor Cell Maturation With Urokinase Plasminogen Activator-Degradable Elastin-like Protein Hydrogels

Guiding Oligodendrocyte Precursor Cell Maturation With Urokinase Plasminogen Activator-Degradable Elastin-like Protein Hydrogels

Hybrid hydrogels for biomedical applications

Engineered microscale hydrogels for drug delivery, cell therapy, and sequencing

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