Harnessing the Properties of Biomaterial to Enhance the Immunomodulation of Mesenchymal Stem Cells

Yin, Chang; Shu, Zhanhao; Qian, Kan; Wang, Jiaxiong; Zhu, Huiyong

doi:10.1089/ten.teb.2019.0131

Cited by 49 publications

(51 citation statements)

References 58 publications

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“…We have seen that 3D hydrogel constructs are more effective in promoting mRNA expression and protein production of soluble immune-related factors than standard 2D conditions 44 . In MSCs cultured in 3D scaffolds, enhanced expression of anti-inflammatory cytokines (Prostaglandin E2-PGE-2, Tumor necrosis factor-inducible gene 6-TSG-6) and reduced expression of pro-inflammatory cytokines (IL-6, Monocyte Chemoattractant Protein 1-MCP-1) was observed 50 . Moreover, WJ-MSCs encapsulated in 3D scaffolds might also reduce the immune response to subcutaneous implantation 44 .…”

Section: Discussionmentioning

confidence: 98%

Biomimetic microenvironmental preconditioning enhance neuroprotective properties of human mesenchymal stem cells derived from Wharton's Jelly (WJ-MSCs)

Lech

Sarnowska

Kuczynska

et al. 2020

Sci Rep

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Tuning stem cells microenvironment in vitro may influence their regenerative properties. In this study Wharton's Jelly-derived mesenchymal stem cells (WJ-MSCs) were encapsulated in 3D hydrogels derived from human fibrin (FB) or platelet lysate (PL) and the oxygen level was adjusted to physiological normoxia (5% O2). The influence of the type of the scaffold and physiological normoxia conditions was tested on the WJ-MSCs' survivability, proliferation, migratory potential, the level of expression of selected trophic factors, cytokines, and neural markers. Encapsulated WJ-MSCs revealed high survivability, stable proliferation rate, and ability to migrate out of the hydrogel and the up-regulated expression of all tested factors, as well as the increased expression of neural differentiation markers. Physiological normoxia stimulated proliferation of encapsulated WJ-MSCs and significantly enhanced their neuronal, but not glial, differentiation. Ex vivo studies with indirect co-culture of organotypic hippocampal slices and cell-hydrogel bio-constructs revealed strong neuroprotective effect of WJ-MSCs against neuronal death in the CA1 region of the rat hippocampus. This effect was potentiated further by FB scaffolds under 5% O2 conditions. Our results indicating significant effect of oxygen and 3D cytoarchitecture suggest the urgent need for further optimization of the microenvironmental conditions to improve therapeutical competence of the WJ-MSCs population.

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Section: Discussionmentioning

confidence: 98%

Biomimetic microenvironmental preconditioning enhance neuroprotective properties of human mesenchymal stem cells derived from Wharton's Jelly (WJ-MSCs)

Lech

Sarnowska

Kuczynska

et al. 2020

Sci Rep

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“…Bone healing is dependent on both biological and mechanical cues and the local environment to which it is subjected. When composite grafting techniques are used i.e., a material together with MSCs or cell aspirate, the physical, chemical and material properties of the carrier/scaffold/coating/device used will determine, in part, the phenotype of the cells (Nava et al, 2012 ; Luangphakdy et al, 2013 ; Hanson et al, 2014 ; Chen et al, 2019 ). Although a detailed discussion of the physical, chemical and material determinants affecting MSC phenotype is beyond the scope of this review, some general points can be made.…”

Section: Methods To Enhance the Function Of Harvested Cells ( mentioning

confidence: 99%

“…These materials are composed of different hydrogels and polymers, mineralized proteins, ceramics, porous metals etc. In clinical scenarios relevant to healing of bone defects, cell fate is determined in part by numerous properties of the materials used including the composition, morphology, viscosity, stiffness, porosity, topography, surface wettability, surface energy, surface charge, molecular attachments, protein absorption and numerous other factors (Wilson et al, 2005 ; Luangphakdy et al, 2013 ; Hanson et al, 2014 ; Bilem et al, 2016 ; Chen et al, 2019 ). For example, in in vitro studies, the topographical differences between 2D and 3D culture conditions have been shown to alter the crosstalk between MSCs and macrophages, and their immune profile (Valles et al, 2015 ).…”

Section: Methods To Enhance the Function Of Harvested Cells ( mentioning

confidence: 99%

Modifying MSC Phenotype to Facilitate Bone Healing: Biological Approaches

Goodman

Lin

2020

Front. Bioeng. Biotechnol.

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Healing of fractures and bone defects normally follows an orderly series of events including formation of a hematoma and an initial stage of inflammation, development of soft callus, formation of hard callus, and finally the stage of bone remodeling. In cases of severe musculoskeletal injury due to trauma, infection, irradiation and other adverse stimuli, deficient healing may lead to delayed or non-union; this results in a residual bone defect with instability, pain and loss of function. Modern methods of mechanical stabilization and autologous bone grafting are often successful in achieving fracture union and healing of bone defects; however, in some cases, this treatment is unsuccessful because of inadequate biological factors. Specifically, the systemic and local microenvironment may not be conducive to bone healing because of a loss of the progenitor cell population for bone and vascular lineage cells. Autologous bone grafting can provide the necessary scaffold, progenitor and differentiated lineage cells, and biological cues for bone reconstruction, however, autologous bone graft may be limited in quantity or quality. These unfavorable circumstances are magnified in systemic conditions with chronic inflammation, including obesity, diabetes, chronic renal disease, aging and others. Recently, strategies have been devised to both mitigate the necessity for, and complications from, open procedures for harvesting of autologous bone by using minimally invasive aspiration techniques and concentration of iliac crest bone cells, followed by local injection into the defect site. More elaborate strategies (not yet approved by the U.S. Food and Drug Administration-FDA) include isolation and expansion of subpopulations of the harvested cells, preconditioning of these cells or inserting specific genes to modulate or facilitate bone healing. We review the literature pertinent to the subject of modifying autologous harvested cells including MSCs to facilitate bone healing. Although many of these techniques and technologies are still in the preclinical stage and not yet approved for use in humans by the FDA, novel approaches to accelerate bone healing by modifying cells has great potential to mitigate the physical, economic and social burden of non-healing fractures and bone defects.

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“…Up to date, numerous strategies, from the modification of culture conditions, the use of bioactive factors (e.g. cytokines, growth factors, small molecules) and harnessing the properties of biomaterials to genetic modification, have been explored to optimize the property and function of MSCs so as to improve their overall therapeutic and regenerative potentials (150,151). Similarly, different approaches have also been explored to optimize the property and function of GMSCs (Table 9).…”

Section: Optimizing the Property And Function Of Gmscsmentioning

confidence: 99%

Gingiva-Derived Mesenchymal Stem Cells: Potential Application in Tissue Engineering and Regenerative Medicine - A Comprehensive Review

Kim

Lee

et al. 2021

Front. Immunol.

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A unique subpopulation of mesenchymal stem cells (MSCs) has been isolated and characterized from human gingival tissues (GMSCs). Similar to MSCs derived from other sources of tissues, e.g. bone marrow, adipose or umbilical cord, GMSCs also possess multipotent differentiation capacities and potent immunomodulatory effects on both innate and adaptive immune cells through the secretion of various types of bioactive factors with immunosuppressive and anti-inflammatory functions. Uniquely, GMSCs are highly proliferative and have the propensity to differentiate into neural cell lineages due to the neural crest-origin. These properties have endowed GMSCs with potent regenerative and therapeutic potentials in various preclinical models of human disorders, particularly, some inflammatory and autoimmune diseases, skin diseases, oral and maxillofacial disorders, and peripheral nerve injuries. All types of cells release extracellular vesicles (EVs), including exosomes, that play critical roles in cell-cell communication through their cargos containing a variety of bioactive molecules, such as proteins, nucleic acids, and lipids. Like EVs released by other sources of MSCs, GMSC-derived EVs have been shown to possess similar biological functions and therapeutic effects on several preclinical diseases models as GMSCs, thus representing a promising cell-free platform for regenerative therapy. Taken together, due to the easily accessibility and less morbidity of harvesting gingival tissues as well as the potent immunomodulatory and anti-inflammatory functions, GMSCs represent a unique source of MSCs of a neural crest-origin for potential application in tissue engineering and regenerative therapy.

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Harnessing the Properties of Biomaterial to Enhance the Immunomodulation of Mesenchymal Stem Cells

Cited by 49 publications

References 58 publications

Biomimetic microenvironmental preconditioning enhance neuroprotective properties of human mesenchymal stem cells derived from Wharton's Jelly (WJ-MSCs)

Biomimetic microenvironmental preconditioning enhance neuroprotective properties of human mesenchymal stem cells derived from Wharton's Jelly (WJ-MSCs)

Modifying MSC Phenotype to Facilitate Bone Healing: Biological Approaches

Gingiva-Derived Mesenchymal Stem Cells: Potential Application in Tissue Engineering and Regenerative Medicine - A Comprehensive Review

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