Matrix decoded – A pancreatic extracellular matrix with organ specific cues guiding human iPSC differentiation

Berger, Constantin; Bjørlykke, Yngvild; Hahn, Lukas; Muhlemann, M.F.; Kreß, Sebastian; Walles, Heike; Luxenhofer, Robert; Ræder, Helge; Metzger, Marco; Zdzieblo, Daniela

doi:10.1016/j.biomaterials.2020.119766

Cited by 25 publications

(29 citation statements)

References 68 publications

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“…Berger et al, highlighted this in a recent study using proteomics to compare the ECM of decellularized porcine pancreas, small intestine, and lung. The study showed clear differences in the ECM signature between decellularized organs and show that organ specific ECM landscapes drive spontaneously differentiating human induced pluripotent stem cells (hiPSCs) toward different lineages in an organ-dependent manner, elegantly revealing that the ECM possesses organspecific biological cues (6).…”

Section: Introductionmentioning

confidence: 97%

Immunomodulatory Role of the Extracellular Matrix Within the Liver Disease Microenvironment

et al. 2020

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Chronic liver disease when accompanied by underlying fibrosis, is characterized by an accumulation of extracellular matrix (ECM) proteins and chronic inflammation. Although traditionally considered as a passive and largely architectural structure, the ECM is now being recognized as a source of potent damage-associated molecular pattern (DAMP)s with immune-active peptides and domains. In parallel, the ECM anchors a range of cytokines, chemokines and growth factors, all of which are capable of modulating immune responses. A growing body of evidence shows that ECM proteins themselves are capable of modulating immunity either directly via ligation with immune cell receptors including integrins and TLRs, or indirectly through release of immunoactive molecules such as cytokines which are stored within the ECM structure. Notably, ECM deposition and remodeling during injury and fibrosis can result in release or formation of ECM-DAMPs within the tissue, which can promote local inflammatory immune response and chemotactic immune cell recruitment and inflammation. It is well described that the ECM and immune response are interlinked and mutually participate in driving fibrosis, although their precise interactions in the context of chronic liver disease are poorly understood. This review aims to describe the known pro-/anti-inflammatory and fibrogenic properties of ECM proteins and DAMPs, with particular reference to the immunomodulatory properties of the ECM in the context of chronic liver disease. Finally, we discuss the importance of developing novel biotechnological platforms based on decellularized ECM-scaffolds, which provide opportunities to directly explore liver ECM-immune cell interactions in greater detail.

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Section: Introductionmentioning

confidence: 97%

Immunomodulatory Role of the Extracellular Matrix Within the Liver Disease Microenvironment

et al. 2020

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“…Thus, any leachables get in direct contact with the cultured cells. Furthermore, construction parts have other requirements than materials for scaffolding in tissue engineering where the induction of biological effects is often wanted [ 14 ]. In contrast to that, construction parts should be inert and prevent cell adhesion as this would cause uncontrolled growth and interfere with the culture process [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

3D Printing of Cell Culture Devices: Assessment and Prevention of the Cytotoxicity of Photopolymers for Stereolithography

et al. 2020

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3D printing is increasingly important for the rapid prototyping of advanced and tailor-made cell culture devices. In this context, stereolithography represents a method for the rapid generation of prototypes from photocurable polymers. However, the biocompatibility of commercially available photopolymers is largely unknown. Therefore, we evaluated the cytotoxicity of six polymers, two of them certified as biocompatible according to ISO 10993-5:2009, and we evaluated, if coating with Parylene, an inert polymer widely used in medical applications, might shield cells from the cytotoxic effects of a toxic polymer. In addition, we evaluated the processability, reliability, and consistency of the details printed. Human mesenchymal stem cells (MSCs) were used for cytotoxicity testing as they are widely used and promising for numerous applications in regenerative medicine. MSCs were incubated together with printed photopolymers, and the cytotoxicity was assessed. All photopolymers significantly reduced the viability of MSCs while the officially biocompatible resins displayed minor toxic effects. Further, coating with Parylene completely protected MSCs from toxic effects. In conclusion, none of the tested polymers can be fully recommended for rapid prototyping of cell culture devices. However, coating with Parylene can shield cells from toxic effects and thus might represent a viable option until more compatible materials are available.

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“…It has been reported that islets and endothelial cells isolated from the human pancreas were seeded in human pancreas ECM scaffolds, respectively, which functioned well and maintained the initial phenotype 19 . In addition, the regulatory effect of porcine pancreatic biological scaffolds on multi‐lineage differentiation of human‐induced pluripotent stem cells has been confirmed, emphasizing the importance of matrix specificity for cell behavior in the artificial microenvironment 20 . Studies showed that porcine pancreatic ECM‐microcapsule encapsulated with human mesenchymal stem cells was nonimmunogenic and significantly controlled the glycemic level in diabetic mice for 2 weeks 21 .…”

Section: Introductionmentioning

confidence: 90%

“…19 In addition, the regulatory effect of porcine pancreatic biological scaffolds on multi-lineage differentiation of human-induced pluripotent stem cells has been confirmed, emphasizing the importance of matrix specificity for cell behavior in the artificial microenvironment. 20 Studies showed that porcine pancreatic ECM-microcapsule encapsulated with human mesenchymal stem cells was nonimmunogenic and significantly controlled the glycemic level in diabetic mice for 2 weeks. 21 At present, ECM hydrogels have been used in tissue repair and reconstruction of heart, 22 cartilage, 23 skin, 24 liver, 25 tendons, 26 dental pulp, 27 and cornea stroma.…”

Section: Introductionmentioning

confidence: 99%

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Pancreatic extracellular matrix and platelet‐rich plasma constructing injectable hydrogel for pancreas tissue engineering

Zhang

Miao²,

Wang

et al. 2020

Artificial Organs

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The development of pancreatic extracellular matrices enriched with insulin-secreting β-cells is a promising tissue engineering approach to treat type 1 diabetes. However, its long-term therapeutic efficacy is restricted by the defensive mechanism of host immune response and the lack of developed vascularization as appropriate after transplantation. Platelet-rich plasma (PRP), as an autologous platelet concentrate, contains a large number of active factors that are essential for the cell viability, vascularization, and immune regulation. In this study, we have incorporated pancreatic extracellular matrix (PEM) with PRP to develop a three-dimensional (3D) injectable PEM-PRP hydrogel to coculture and transplant rat insulinoma cells (INS-1) and human umbilical vein endothelial cells (HUVECs). Results from this study demonstrated that PEM-PRP hydrogel mimicked the biochemical compositions of native extracellular matrices, and possessed the enhanced elastic modulus and resistance to enzymatic degradation that enabled biomaterials to maintain its volume and slowly degrade. Additionally, PEM-PRP hydrogel could release growth factors in a sustained manner. In vitro, PEM-PRP hydrogel significantly promoted the viability, insulin-secreting function, and insulin gene expression of gel encapsulated INS-1 cells. Moreover, HUVECs encapsulated in PEM-PRP hydrogel were found to constitute many lumen-like structures and exhibited high expression of proangiogenic genes. In vivo transplantation of PEM-PRP hydrogel encapsulated with INS-1 cells and HUVECs improved the viability of INS-1 cells, promoted vascularization, inhibited the host inflammatory response, and reversed hyperglycemia of diabetic rats. Our study suggests that the PEM-PRP hydrogel offers excellent biocompatibility and proangiogenic property, and may serve as an effective biomaterial platform to maintain the long-term survival and function of insulin-secreting β cells.

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Matrix decoded – A pancreatic extracellular matrix with organ specific cues guiding human iPSC differentiation

Cited by 25 publications

References 68 publications

Immunomodulatory Role of the Extracellular Matrix Within the Liver Disease Microenvironment

Immunomodulatory Role of the Extracellular Matrix Within the Liver Disease Microenvironment

3D Printing of Cell Culture Devices: Assessment and Prevention of the Cytotoxicity of Photopolymers for Stereolithography

Pancreatic extracellular matrix and platelet‐rich plasma constructing injectable hydrogel for pancreas tissue engineering

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