Mesenchymal stem cell (MSC)-derived exosomes have been recognized as new candidates for cell-free treatment of various diseases. However, maintaining the retention and stability of exosomes over time in vivo after transplantation is a major challenge in the clinical application of MSC-derived exosomes. Here, we investigated if human placenta-derived MSC-derived exosomes incorporated with chitosan hydrogel could boost the retention and stability of exosomes and further enhance their therapeutic effects. Our results demonstrated that chitosan hydrogel notably increased the stability of proteins and microRNAs in exosomes, as well as augmented the retention of exosomes in vivo as confirmed by Gaussia luciferase imaging. In addition, we assessed endothelium-protective and proangiogenesis abilities of hydrogel-incorporated exosomes in vitro. Meanwhile, we evaluated the therapeutic function of hydrogel-incorporated exosomes in a murine model of hindlimb ischemia. Our data demonstrated that chitosan hydrogel could enhance the retention and stability of exosomes and further augment the therapeutic effects for hindlimb ischemia as revealed by firefly luciferase imaging of angiogenesis. The strategy used in this study may facilitate the development of easy and effective approaches for assessing and enhancing the therapeutic effects of stem cell-derived exosomes.

Stem cell therapy is a promising alternative approach to the treatment of a number of incurable degenerative diseases. However, low cell retention and survival after transplantation limit the therapeutic efficacy of stem cells for clinical translational applications. The utilization of biomaterials has been progressively successful in controlling the fate of transplanted cells by imitating the cellular microenvironment for optimal tissue repair and regeneration. This review mainly focuses on the engineered microenvironments with synthetic biomaterials in modification of stem cell behaviors. Moreover, the possible advancements in translational therapy by using biomaterials with stem cells are prospected and the challenges of the current restriction in clinical applications are highlighted.

Background The senescence of dermal fibroblasts (DFLs) leads to an imbalance in the synthesis and degradation of extracellular matrix (ECM) proteins, presenting so-called senescence-associated secretory phenotype (SASP), which ultimately leads to skin aging. Recently, mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have been recognized as a promising cell-free therapy for degenerative diseases, which opens a new avenue for skin aging treatment. Methods In this study, we utilized chitosan (CS) hydrogel for effective loading and sustained release of EVs. In vitro, we explored the rejuvenation effects of CS hydrogel-incorporated EVs (CS-EVs) on replicative senescence DFLs through a series of experiments such as senescence-associated β-galactosidase (SA-β-gal) staining, RT-PCR, and Western blot analysis. Besides, we employed local multi-site subcutaneous injection to treat skin aging of naturally aged mice with CS-EVs and DiI fluorescent dye was used to label EVs to achieve in vivo real-time tracking. Results CS-EVs can significantly improve the biological functions of senescent fibroblasts, including promoting their proliferation, enhancing the synthesis of ECM proteins, and inhibiting the overexpression of matrix metalloproteinases (MMPs). Moreover, CS hydrogel could prolong the release of EVs and significantly increase the retention of EVs in vivo. After CS-EVs subcutaneous injection treatment, the aging skin tissues showed a rejuvenation state, manifested explicitly as the enhanced expression of collagen, the decreased expression of SASP-related factors, and the restoration of tissue structures. Conclusions CS hydrogel-encapsulated EVs could delay the skin aging processes by ameliorating the function of aging DFLs. Our results also highlight the potential of CS hydrogel-encapsulated EVs as a novel therapeutic strategy for improving aging skin to rejuvenation.

Adenosine-to-inosine (A-to-I) RNA editing and the catalyzing enzyme adenosine deaminase are both essential for hematopoietic development and differentiation. However, the RNA editome during hematopoiesis and the underlying mechanisms are poorly defined. Here, we sorted 12 murine adult hematopoietic cell populations at different stages and identified 30,796 editing sites through RNA sequencing. While the dynamic landscape of the RNA editome comprised of stage/group-specific and stable editing patterns, but also undergoing significant changes during lineage commitment. Notably, we found that antizyme inhibitor 1 (Azin1) was highly edited in hematopoietic stem and progenitor cells (HSPCs). Azin1 editing results in: (i) an amino acid change to induce Azin1 protein (AZI) translocation to the nucleus, (ii) enhanced AZI binding affinity for DEAD box polypeptide 1 (DDX1) to alter the chromatin distribution of the latter, and (iii) altered expression of multiple hematopoietic regulators which ultimately promotes HSPC differentiation. Our findings have delineated an essential role for Azin1 RNA editing in hematopoietic cells, and our dataset constitutes a valuable resource for further study of RNA editing on a more general basis.

Mesenchymal stem cell (MSC)-derived exosomes have been recognized as new candidates for cell-free treatment of various diseases. However, maintaining the retention and stability of exosomes over time in vivo after transplantation is a major challenge in clinical application of MSC-derived exosomes. Here, we investigated if human placenta-derived MSCs (hP-MSCs) derived exosomes incorporated with chitosan hydrogel could boost the retention and stability of exosomes and further enhance their therapeutic effect. Our results demonstrated that chitosan hydrogel notably increased the stability of proteins and microRNAs in exosomes, as well as augmented the retention of exosomes in vivo as confirmed by Gaussia luciferase imaging. In addition, we evaluated the therapeutic function of hP-MSCs derived exosomes incorporated with chitosan hydrogel in a murine model of hindlimb ischemia. Our data demonstrated that chitosan hydrogel could enhance the retention of exosomes and further augment the therapeutic effects for hindlimb ischemia as revealed by firefly luciferase imaging of angiogenesis. The strategy used in this study may facilitate the development of easy and effective approaches for assessing and enhancing the therapeutic effects of stem cell-derived exosomes.

Background: The senescence of dermal fibroblasts (DFLs) leads to an imbalance in the synthesis and degradation of extracellular matrix (ECM) proteins, presenting so-called senescence-associated secretory phenotype (SASP), which ultimately leads to skin aging. Recently increasing evidence has supported the idea that mesenchymal stem cells (MSCs) derived extracellular vesicles (MSC-EVs) opened a new avenue for treating skin aging.Methods: In this study, we utilized chitosan (CS) hydrogel for effective loading and sustained release of EVs. In vitro, we explored the rejuvenation effects of CS hydrogel-incorporated EVs (CS-EVs) on replicative senescence DFLs through a series of experiments such as senescence-associated β-galactosidase (SA-β-gal) staining, RT-PCR, and western blots. Besides, we employed local multi-site subcutaneous injection to treat the back skin of naturally aging mice with CS-EVs and used DiI fluorescent dye to label EVs to achieve in vivo real-time tracking.Results: CS-EVs can significantly improve the biological functions of senescent fibroblasts, including promoting their proliferation, enhancing the synthesis of ECM proteins, and inhibiting the overexpression of matrix metalloproteinases (MMPs). Moreover, CS hydrogel could prolong the release of EVs and significantly increase the retention rate of EVs in vivo. After CS-EVs subcutaneous injection treatment, the aging skin tissues showed a state of rejuvenation, which was specifically manifested as enhanced expression of collagen, decreased expression of SASP-related factors, and restoration of tissue structures.Conclusions: CS hydrogel-encapsulated EVs could delay the skin aging process by ameliorating the function of aging DFLs. Our results also highlight the potential of CS hydrogel-encapsulated EVs as a novel therapeutic strategy for ameliorating aging skin to rejuvenation.

An optical phase modulator based on novel n-i-n InGaAlAs/InAlAs multiple-quantum-barrier (MQBs) is proposed to reduce the waveguide loss and enhance the modulation efficiency. Efficient bias loading with low leakage current is realized by taking advantages of the large conduction band discontinuity in InGaAlAs/InAlAs heterostructure and high electron reflection by MQBs. Low optical transmission loss of 2.3 dB/cm and improved modulation performance with a voltage length product of 1.06 V⋅cm are demonstrated for TE mode at 1550 nm. The linear and quadratic electro-optic coefficients of the fabricated device are estimated to be 1.0 pm/V and 1.4 × 10⁻¹⁹ m²/V², respectively.

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