Stem cells, including mesenchymal stem cells and pluripotent stem cells, have attracted considerable attention in tissue engineering and regenerative medicine primarily because of their unique ability in self-renewal and multilineage differentiation. However, stem cells also have important secretory functions that form a specialized in vivo microenvironment and direct tissue development and regeneration. Extracellular matrices (ECMs) derived from stem cells retain the functional properties of their native environment and exhibit unique signaling that mediates stem cell self-renewal and lineage commitment. Stem cell-derived ECMs (scECMs) also have tunable properties corresponding to their developmental stages, suggesting that their lineage-and developmental specificity can be engineered for a wide range of applications. Hence, there is a growing interest in reconstructing stem cell microenvironment through decellularization and obtaining decellularized matrices that exhibit unique biological properties. This article summarizes recent advances in the use and understanding of scECMs. Moreover, future directions to extend the spectrum of applications of stem-derived ECMs in tissue engineering by comprehensively elucidating and engineering their regulatory function is highlighted.

Human mesenchymal stem cells (hMSCs) are a promising candidate in cell therapy as they exhibit multilineage differentiation, homing to the site of injury, and secretion of trophic factors that facilitate tissue healing and/or modulate immune response. As a result, hMSC-derived products have attracted growing interests in preclinical and clinical studies. The development of hMSC culture platforms for large-scale biomanufacturing is necessary to meet the requirements for late-phase clinical trials and future commercialization. Microcarriers in stirred-tank bioreactors have been widely utilized in large-scale expansion of hMSCs for translational applications because of a high surface-to-volume ratio compared to conventional 2D planar culture. However, recent studies have demonstrated that microcarrier-expanded hMSCs differ from dish-or flask-expanded cells in size, morphology, proliferation, viability, surface markers, gene expression, differentiation potential, and secretome profile which may lead to altered therapeutic potency. Therefore, understanding the bioprocessing parameters that influence hMSC therapeutic efficacy is essential for the optimization of microcarrier-based bioreactor system to maximize hMSC quantity without sacrificing quality. In this review, biomanufacturing parameters encountered in planar culture and microcarrier-based bioreactor culture of hMSCs are compared and discussed with specific focus on cell-adhesion surface (e.g., discontinuous surface, underlying curvature, microcarrier stiffness, porosity, surface roughness, coating, and charge) and the dynamic microenvironment in bioreactor culture (e.g., oxygen and nutrients, shear stress, particle collision, and aggregation). The influence of dynamic culture in bioreactors on hMSC properties is also reviewed in order to establish connection between bioprocessing and stem cell function. This review addresses fundamental principles and concepts for future design of biomanufacturing systems for hMSCbased therapy.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive cell loss, largely confined to mesencephalic dopamine neurons of the substantia nigra. This study investigated the functional relevance of the HOX transcript antisense intergenic RNA (HOTAIR)/microRNA-221-3 (miR-221-3p)/neuronal pentraxin II (NPTX2) axis in the process of dopaminergic neuron autophagy using PD mouse models. The PD mouse models were established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP), while PD cell model was constructed by pretreatment with 1-methyl-4-phenylpyridinium (MPP +). The expression of HOTAIR was then examined using RT-qPCR. In addition, the interactions between HOTAIR, miR-221-3p, and NPTX2 were detected through RIP and dual-luciferase reporter gene assays. CCK-8 assay was performed to measure cell viability, and the expression of autophagy-related genes was determined using Western blot analysis. HOTAIR was found to be significantly expressed in the substantia nigra compact tissues and MN9D cells following PD modeling. HOTAIR could bind to miR-221-3p and elevate the NPTX2 expression, which resulted in diminished cell viability and enhanced autophagy of dopaminergic neurons both in vitro and in vivo. In summary, down-regulation of HOTAIR could potentially inhibit the autophagy of dopaminergic neurons in the substantia nigra compacta in a mouse model of PD, thus saving the demise of dopaminergic neurons. .

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