Decellularized Extracellular Matrix as an In Vitro Model to Study the Comprehensive Roles of the ECM in Stem Cell Differentiation

Abstract

Stem cells are a promising cell source for regenerative medicine. Stem cell differentiation must be regulated for applications in regenerative medicine. Stem cells are surrounded by extracellular matrix (ECM) in vivo. The ECM is composed of many types of proteins and glycosaminoglycans that assemble into a complex structure. The assembly of ECM molecules influences stem cell differentiation through orchestrated intracellular signaling activated by many ECM molecules. Therefore, it is important to understand the comprehensive role of the ECM in stem cell differentiation as well as the functions of the individual ECM molecules. Decellularized ECM is a useful in vitro model for studying the comprehensive roles of ECM because it retains a native-like structure and composition. Decellularized ECM can be obtained from in vivo tissue ECM or ECM fabricated by cells cultured in vitro. It is important to select the correct decellularized ECM because each type has different properties. In this review, tissue-derived and cell-derived decellularized ECMs are compared as in vitro ECM models to examine the comprehensive roles of the ECM in stem cell differentiation. We also summarize recent studies using decellularized ECM to determine the comprehensive roles of the ECM in stem cell differentiation.

“Tissue Papers” from Organ‐Specific Decellularized Extracellular Matrices

“…This indicates that the tissue-specific nature of the TPs is having an impact on cell morphology and behavior, which is in accordance with previously described observations of the effects of tissue-specific dECMs on cell behavior. [11] However, further comprehensive investigations will need to be conducted to determine the exact nature and influence of TP type on the phenotype of hMSCs as well as tissue specific cell types. By day 28 (Figure 5 and Figure S5 (Supporting Information)), the cells on all TPs had proliferated to confluently cover both the top seeded and underside of the TPs.…”

“…This long track record and acceptance by clinicians is indicative of the promise of new ECM-based biomaterials that can be applied to repair or regenerate damaged, missing, or dysfunctional tissues and organs without activating host immune response, [1] or even serve as model materials for in vitro healthy or diseased tissue modeling. [11,12] Despite dECM’s demonstrated advantages as a raw material and promise for use in an extensive range of tissue and organ targets including but not limited to: heart, [13] muscle, [1,14] nerve, [15] liver, [3,16,17] lung, [18,19] kidney, [4,20] bone, [21] skin, [22] bladder, [23] ovary, [24] and penis, [25] the existing processing routes for creating diverse sets of clinically practical, tissue-specific dECM-based biomaterials remain limited.…”

Perivascular extracellular matrix hydrogels mimic native matrix microarchitecture and promote angiogenesis via basic fibroblast growth factor

“…[13-17] Additionally, degradation of ECM bioscaffolds releases matricryptic peptides that invoke biologic activity. [18] ECM bioscaffolds guide stem cell differentiation through growth factor retention and unique matrix compliance, [19-23] which together comprise tissue-specific microenvironments that are advantageous for regeneration. [24]…”

Biofunctionalized Plants as Diverse Biomaterials for Human Cell Culture

“…The most desirable scaffolds include interconnected porosity for fluid transport, biochemical properties that support cell function, and a diversity of physical and mechanical properties that can be customized for specific biological or medical needs. Recent advanced manufacturing approaches, such as 3-D printing or decellularization of animal tissues, have produced scaffolds with biomimetic [1] or unique physical properties [2] . Despite these advances, the ability to manufacture biomaterials with a diverse range of achievable physical and biological properties remains a challenge and an active area of inquiry [3] .…”

“…The use of detergents in decellularization protocols is common practice and they are widely used to decellularize tissue-derived ECM [12] [1] or even plant tissues [13] . Decellularized Petroselinum crispum (parsley) stems showed a more translucent appearance due to the loss of the plant’s pigments and waxy cuticle, and also had a markedly decreased DNA content when compared to non-decellularized parsley stems (Figure 1b–c, Supplementary Figure 1).…”