Delivery of Differentiation Factors by Mesoporous Silica Particles Assists Advanced Differentiation of Transplanted Murine Embryonic Stem Cells

Garcia‐Bennett, Alfonso E.; Kozhevnikova, M. N.; König, Niclas; Zhou, Chunfang; Leão, Richardson N.; Knöpfel, Thomas; Pankratova, Stanislava; Trolle, Carl; Berezin, Vladimir; Bock, Elisabeth; Aldskogius, Håkan; Kozlova, Elena N.

doi:10.5966/sctm.2013-0072

Cited by 33 publications

(22 citation statements)

References 24 publications

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“…Gliafin (153-ETMYDKILKNLSRSR-167; UniProtKB entry no. Q07731) is a small peptide that displays GDNFlike activity and was recently demonstrated to induce efficient differentiation and functional integration of transplanted stem cell derivatives [81]. It has not been tested yet as an alternative to GDNF in local delivery experimental paradigms of inflammatory or neuropathic pain, but it deserves further attention as a possible GDNF therapeutic substitute.…”

Section: Gfl Mimetics and Small Molecules Targeting The Gfls' Receptorsmentioning

confidence: 99%

“…Based on the previously discussed evidence of animal studies, and considering that GDNF has been demonstrated to undergo both retrograde and anterograde transport in neurons [10,31] it seems reasonable that, broadly-speaking, a GDNF-related therapy may be effective at both peripheral and central levels. In addition, as minimally invasive topical or systemic routes of administration other than the direct delivery into the central or the peripheral neurons have proved to be efficacious in animal models [4,64,[81][82][83], it seems desirable that these routes are explored in clinical settings too.…”

Section: Expert Opinionmentioning

confidence: 99%

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Targeting the glial-derived neurotrophic factor and related molecules for controlling normal and pathologic pain

Merighi

2015

Expert Opinion on Therapeutic Targets

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Introduction: GDNF and its family of ligands (GFLs) have several functions in the nervous system. As a survival factor for dopaminergic neurons, GDNF was used in clinical trials for Parkinson's disease. However, GFLs their receptors are potential targets for new pain-controlling drugs. Such a potential should not be underestimated because molecules with analgesic activities in rodents mostly failed to be effective in translational studies. Areas covered:The circuitry, molecular and cellular mechanisms by which GFLs control nociception, their intervention in inflammatory and neuropathic pain, the problems related to effective GDNF delivery to the brain, the possibility to target the GFL receptor complex rather than its ligands, also by the use of non-peptidyl agonists, are discussed. Expert opinion:In nociceptive pathways, an ideal drug should either: i. Target the release of endogenous GFLs from large dense-cored vesicles (LGVs) by acting e.g. onto the phosphatidylinositol-3-phosphate [PtdIns(3)P] pool, which is sensitive to Ca 2+ modulation; ii. Target the GFL receptor complex. Besides to XIB403, a thiol molecule that enhances GFRα family receptor signaling, existing drugs such as retinoic acid and amitriptyline should be considered for effective targeting of GDNF, at least in neuropathic pain. The approach of pain modeling in experimental animals is discussed.

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Section: Gfl Mimetics and Small Molecules Targeting The Gfls' Receptorsmentioning

confidence: 99%

Section: Expert Opinionmentioning

confidence: 99%

Targeting the glial-derived neurotrophic factor and related molecules for controlling normal and pathologic pain

Merighi

2015

Expert Opinion on Therapeutic Targets

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“…Moreover, nanoporous MSPs hold the potential to be not only a very efficient but also a cost effective drug delivery system. We previously showed that MSPs loaded with growth factor mimetics promote survival and differentiation of co-implanted neural stem cells, 7 indicating that the MSP delivery system can serve as a valuable tool for controlling differentiation of transplanted stem cells. Toxicological data from in vitro and in vivo studies suggest that unloaded MSPs have no observable harmful effects and are well tolerated.…”

Section: Introductionmentioning

confidence: 99%

The Effect of Mesoporous Silica Particles on Stem Cell Differentiation

Kozlova¹

2017

JSRT

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Abbreviations: bNCSC, boundary cap neural crest stem cell; DIFF, differentiation medium; eGFP, enhanced green fluorescent protein; GFAP, glial fibrillary acidic protein; Iba-1, ionized calcium binding adaptor molecule 1; MSP, mesoporous silica particle; PBS, phosphate buffered saline; TRITC, tetramethylrhodamine-5-(and 6)-isothiocyanate; Vol, volume; Wt, weight IntroductionMesoporous silica particles (MSPs) are characterized by ordered porosity, sharp pore size distributions, high internal surface areas, and large pore volumes. 1,2 Control over these structural parameters makes them an ideal candidate for drug encapsulation, perfectly suited to uptake and carry large amounts of drugs that then get released with constant concentration. [3][4][5] The release of the actives can be diffusion controlled or may be triggered by a change in media temperature or pH.6 Creation of simultaneous release profiles is possible by using different pore structures (e. g., 2D hexagonal and 3D cubic) that enable a continuous discharge of a fine tuned mixture of active drugs over a given period of time.MSPs have already shown potential for life science applications over traditional polymer based delivery systems. They offer increased bioavailability, biocompatibility, controlled and targeted release, reduced drug-drug interactions, the potential to deliver both lipophilic and hydrophilic drugs simultaneously, and the ability to customize release profiles for a combination of drugs. Moreover, nanoporous MSPs hold the potential to be not only a very efficient but also a cost effective drug delivery system. We previously showed that MSPs loaded with growth factor mimetics promote survival and differentiation of co-implanted neural stem cells, 7 indicating that the MSP delivery system can serve as a valuable tool for controlling differentiation of transplanted stem cells. Toxicological data from in vitro and in vivo studies suggest that unloaded MSPs have no observable harmful effects and are well tolerated. [8][9][10] However the possible influence of MSPs, used in our studies, on stem cell differentiation and on the non-neuronal response in the central nervous system has not been examined previously. Here we tested the effect of unloaded MSPs on in vitro differentiation of boundary cap neural crest stem cells (bNCSCs), a source of stem cells with remarkable therapeutic potential, and also analyzed the fate of MSPs at different time points after implantation into the spinal cord and on its surface. bNCSCs are neural crest derivatives that populate the entry/ exit points of spinal roots during embryonic development, 11,12 participate in cell migration and axon growth control at the spinal root-spinal cord interface, [13][14][15] AbstractStem cell transplantation is an attractive strategy to counteract the progression of neurodegenerative disorders and to replace lost neuronal cells. Despite successful generation of neuronal cell types in vitro, stem cell technology typically fails when applied in vivo. One of the reasons is lack of cont...

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“…53,66,134 MSNs undergo endocytosis in cells, including MSCs, with no adverse effect on differentiation, viability, and proliferation. 33 The large pore volume and surface area allows for nucleic acid, peptides, and polymers to be adsorbed, trapped, or bound.…”

Section: Silica-based Particlesmentioning

confidence: 99%

Monitoring/Imaging and Regenerative Agents for Enhancing Tissue Engineering Characterization and Therapies

et al. 2015

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The past three decades have seen numerous advances in tissue engineering and regenerative medicine (TERM) therapies. However, despite the successes there is still much to be done before TERM therapies become commonplace in clinic. One of the main obstacles is the lack of knowledge regarding complex tissue engineering processes. Imaging strategies, in conjunction with exogenous contrast agents, can aid in this endeavor by assessing in vivo therapeutic progress. The ability to uncover real-time treatment progress will help shed light on the complex tissue engineering processes and lead to development of improved, adaptive treatments. More importantly, the utilized exogenous contrast agents can double as therapeutic agents. Proper use of these Monitoring/Imaging and Regenerative Agents (MIRAs) can help increase TERM therapy successes and allow for clinical translation. While other fields have exploited similar particles for combining diagnostics and therapy, MIRA research is still in its beginning stages with much of the current research being focused on imaging or therapeutic applications, separately. Advancing MIRA research will have numerous impacts on achieving clinical translations of TERM therapies. Therefore, it is our goal to highlight current MIRA progress and suggest future research that can lead to effective TERM treatments.

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Delivery of Differentiation Factors by Mesoporous Silica Particles Assists Advanced Differentiation of Transplanted Murine Embryonic Stem Cells

Cited by 33 publications

References 24 publications

Targeting the glial-derived neurotrophic factor and related molecules for controlling normal and pathologic pain

Targeting the glial-derived neurotrophic factor and related molecules for controlling normal and pathologic pain

The Effect of Mesoporous Silica Particles on Stem Cell Differentiation

Monitoring/Imaging and Regenerative Agents for Enhancing Tissue Engineering Characterization and Therapies

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