Toward Customized Extracellular Niche Engineering: Progress in Cell‐Entrapment Technologies

Thomas, Dilip; O’Brien, Timothy; Pandit, Abhay

doi:10.1002/adma.201703948

Cited by 48 publications

(42 citation statements)

References 219 publications

(208 reference statements)

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“…Tissue damage leads to the disturbing of niches, which can be the reason why tissue or organ cannot recover completely. Many approaches are aimed to creating a biomaterial similar to the natural microenvironment (Donnelly et al, 2018;Hagbard et al, 2018;Thomas et al, 2018;Shrestha and Yoo, 2019). The difficulty lies in the selection of niche components that could be crucial for reconstruction of naïve microenvironment.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal Stromal Cell-Produced Components of Extracellular Matrix Potentiate Multipotent Stem Cell Response to Differentiation Stimuli

Novoseletskaya

Grigorieva

Nimiritsky

et al. 2020

Front. Cell Dev. Biol.

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Extracellular matrix (ECM) provides both structural support and dynamic microenvironment for cells regulating their behavior and fate. As a critical component of stem cell niche ECM maintains stem cells and activates their proliferation and differentiation under specific stimuli. Mesenchymal stem/stromal cells (MSCs) regulate tissue-specific stem cell functions locating in their immediate microenvironment and producing various bioactive factors, including ECM components. We evaluated the ability of MSC-produced ECM to restore stem and progenitor cell microenvironment in vitro and analyzed the possible mechanisms of its effects. Human MSC cell sheets were decellularized by different agents (detergents, enzymes, and apoptosis inductors) to select the optimized combination (CHAPS and DNAse I) based on the conservation of decellularized ECM (dECM) structure and effectiveness of DNA removal. Prepared dECM was non-immunogenic, supported MSC proliferation and formation of larger colonies in colony-forming unit-assay. Decellularized ECM effectively promoted MSC trilineage differentiation (adipogenic, osteogenic, and chondrogenic) compared to plastic or plastic covered by selected ECM components (collagen, fibronectin, laminin). Interestingly, dECM produced by human fibroblasts could not enhance MSC differentiation like MSC-produced dECM, indicating cell-specific functionality of dECM. We demonstrated the significant integrin contribution in dECM-cell interaction by blocking the stimulatory effects of dECM with RGD peptide and suggested the involvement of key intracellular signaling pathways activation (pERK/ERK and pFAK/FAK axes, pYAP/YAP and beta-catenin) in the observed processes based on the results of inhibitory analysis. Taken together, we suppose that MSC-produced dECM may mimic stem cell niche components in vitro and maintain multipotent progenitor cells to insure their effective response to external differentiating stimuli upon activation. The obtained data provide more insights into the possible role of MSC-produced ECM in stem and progenitor cell regulation within their niches. Our results are also useful for the developing of dECM-based cell-free products for regenerative medicine.

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Section: Discussionmentioning

confidence: 99%

Mesenchymal Stromal Cell-Produced Components of Extracellular Matrix Potentiate Multipotent Stem Cell Response to Differentiation Stimuli

Novoseletskaya

Grigorieva

Nimiritsky

et al. 2020

Front. Cell Dev. Biol.

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“…In the literature, a paracrine-centric mechanism via release of cytokines, chemokines, and growth factors by MSCs and its role in high cell survival (1), recruitment of endothelial progenitors (2), and angiogenesis (3,4) has been demonstrated (5). Several tissue-engineering technologies have exploited the paracrine properties of MSCs via cell-immobilization strategies, with the aim of using cells as local drug-delivery depots to secrete beneficial factors to induce reparative angiogenesis (6). However, little is currently known about the stem-cell phenotype and behavior as a result of in vitro preconditioning in artificially engineered extracellular matrices (ECMs).…”

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confidence: 99%

Temporal changes guided by mesenchymal stem cells on a 3D microgel platform enhance angiogenesis in vivo at a low-cell dose

Thomas

Marsico

Isa

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Therapeutic factors secreted by mesenchymal stem cells (MSCs) promote angiogenesis in vivo. However, delivery of MSCs in the absence of a cytoprotective environment offers limited efficacy due to low cell retention, poor graft survival, and the nonmaintenance of a physiologically relevant dose of growth factors at the injury site. The delivery of stem cells on an extracellular matrix (ECM)-based platform alters cell behavior, including migration, proliferation, and paracrine activity, which are essential for angiogenesis. We demonstrate the biophysical and biochemical effects of preconditioning human MSCs (hMSCs) for 96 h on a three-dimensional (3D) ECM-based microgel platform. By altering the macromolecular concentration surrounding cells in the microgels, the proangiogenic phenotype of hMSCs can be tuned in a controlled manner through cell-driven changes in extracellular stiffness and “outside-in” integrin signaling. The softest microgels were tested at a low cell dose (5 × 104 cells) in a preclinical hindlimb ischemia model showing accelerated formation of new blood vessels with a reduced inflammatory response impeding progression of tissue damage. Molecular analysis revealed that several key mediators of angiogenesis were up-regulated in the low-cell-dose microgel group, providing a mechanistic insight of pathways modulated in vivo. Our research adds to current knowledge in cell-encapsulation strategies by highlighting the importance of preconditioning or priming the capacity of biomaterials through cell–material interactions. Obtaining therapeutic efficacy at a low cell dose in the microgel platform is a promising clinical route that would aid faster tissue repair and reperfusion in “no-option” patients suffering from peripheral arterial diseases, such as critical limb ischemia (CLI).

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“…For further reading on these specific design requirements, we refer to excellent recent reviews. [216][217][218][219][220] However, it is clear that these design requirements are now a next logical step for advancing bioinks toward functional and bioactive bioinks that can, at least partially, orchestrate cellular behavior postprocessing.…”

Section: Next Generation Bioinksmentioning

confidence: 99%

From Shape to Function: The Next Step in Bioprinting

et al. 2020

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In 2013, the “biofabrication window” was introduced to reflect the processing challenge for the fields of biofabrication and bioprinting. At that time, the lack of printable materials that could serve as cell‐laden bioinks, as well as the limitations of printing and assembly methods, presented a major constraint. However, recent developments have now resulted in the availability of a plethora of bioinks, new printing approaches, and the technological advancement of established techniques. Nevertheless, it remains largely unknown which materials and technical parameters are essential for the fabrication of intrinsically hierarchical cell–material constructs that truly mimic biologically functional tissue. In order to achieve this, it is urged that the field now shift its focus from materials and technologies toward the biological development of the resulting constructs. Therefore, herein, the recent material and technological advances since the introduction of the biofabrication window are briefly summarized, i.e., approaches how to generate shape, to then focus the discussion on how to acquire the biological function within this context. In particular, a vision of how biological function can evolve from the possibility to determine shape is outlined.

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Toward Customized Extracellular Niche Engineering: Progress in Cell‐Entrapment Technologies

Cited by 48 publications

References 219 publications

Mesenchymal Stromal Cell-Produced Components of Extracellular Matrix Potentiate Multipotent Stem Cell Response to Differentiation Stimuli

Mesenchymal Stromal Cell-Produced Components of Extracellular Matrix Potentiate Multipotent Stem Cell Response to Differentiation Stimuli

Temporal changes guided by mesenchymal stem cells on a 3D microgel platform enhance angiogenesis in vivo at a low-cell dose

From Shape to Function: The Next Step in Bioprinting

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