MOF-encapsulated nanozyme enhanced siRNA combo: Control neural stem cell differentiation and ameliorate cognitive impairments in Alzheimer's disease model

Yu, Dongqin; Ma, Mengmeng; Liu, Zhengwei; Pi, Zifeng; Du, Xiubo; Ren, Jinsong; Qu, Xiaogang

doi:10.1016/j.biomaterials.2020.120160

Cited by 150 publications

(81 citation statements)

References 63 publications

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“…The transformation of the retinoic acid precursor into RA requires oxidation, which is performed by ALDH1A1 [ 29 , 30 ]. Subsequently, RA can trigger the differentiation of stem/progenitor cells such as hematopoietic stem cells [ 31 ], neural progenitor cells [ 32 , 33 ], and embryonic stem cells [ 34 ]). Herein, the first step in the RA pathway was further studied.…”

Section: Resultsmentioning

confidence: 99%

Bio-inspired chiral self-assemblies promoted neuronal differentiation of retinal progenitor cells through activation of metabolic pathway

Sun

Dou

Tang

et al. 2021

Bioactive Materials

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Retinal degeneration is a main class of ocular diseases. So far, retinal progenitor cell (RPC) transplantation has been the most potential therapy for it, in which promoting RPCs neuronal differentiation remains an unmet challenge. To address this issue, innovatively designed L/ d - phenylalanine based chiral nanofibers (LPG and DPG) are employed and it finds that chirality of fibers can efficiently regulate RPCs differentiation. qPCR, western blot, and immunofluorescence analysis show that right-handed helical DPG nanofibers significantly promote RPCs neuronal differentiation, whereas left-handed LPG nanofibers decrease this effect. These effects are mainly ascribed to the stereoselective interaction between chiral helical nanofibers and retinol-binding protein 4 (RBP4, a key protein in the retinoic acid (RA) metabolic pathway). The findings of chirality-dependent neuronal differentiation provide new strategies for treatment of neurodegenerative diseases via optimizing differentiation of transplanted stem cells on chiral nanofibers.

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Section: Resultsmentioning

confidence: 99%

Bio-inspired chiral self-assemblies promoted neuronal differentiation of retinal progenitor cells through activation of metabolic pathway

Sun

Dou

Tang

et al. 2021

Bioactive Materials

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“…In their study, metal–organic frameworks (MOF)‐aided NSC therapy promoted the neuronal differentiation of transplanted NSCs and ameliorated cognitive impairments in AD mice. [ 46 ] The combined neuronal differentiation promotion and antioxidation of the MOF‐aided NSC therapy showed an excellent curative effect in a short‐term (≈1 month). However, without solving the Aβ pathology and the viability of transplanted NSCs, the long‐term therapeutic efficacy of this therapy for AD is unknown.…”

Section: Figurementioning

confidence: 99%

A Nanoformulation‐Mediated Multifunctional Stem Cell Therapy with Improved Beta‐Amyloid Clearance and Neural Regeneration for Alzheimer's Disease

et al. 2021

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neurofibrillary tangles, and neuroinflammation, which progressively cause the loss of neurons and synaptic connectivity in the brain. [1,3-6] At present, AD is still incurable and existing treatments can only moderately relieve its symptoms. Current AD therapies, including anti-Aβ, anti-tau, and immune modulation, are only effective in preventing or delaying the development of AD in patients with very early pathology, but ineffective for slowing cognitive decline in patients who already have significant impairment. [1,6,7] The failures of these therapies are partly due to their inability to regenerate the lost neurons in the brains of symptomatic patients. Recently, stem cell-based regenerative therapy has shown great potential for AD treatment, given its ability to regenerate damaged neural networks in the brain by generating functional neural cells and integrating them into the existing synaptic network. [8-12] Moreover, several clinical trials have demonstrated the safety of stem cell-based therapies, [9,13] although they still face several challenges. First, the hostile environment in the AD brain adversely affects the survival and propagation of transplanted neural stem cells (NSCs), limiting effects to the short term. [9,14,15] Second, although NSCs are able to enhance synaptic connections through regenerating neurons, they do not have a strong ability to clear Aβ and Tau, and therefore cannot effectively treat the pathologies caused by their accumulation. [16] Third, due to the adverse pathological microenvironment of AD-particularly the high concentration of toxic Aβ oligomers-the neuronal differentiation of NSCs is inhibited, reducing neural regeneration in the brain. [16,17] Therefore, numerous efforts have been made to enhance the therapeutic capabilities (Aβ clearance and immune modulation) [1,7,16] and neuronal differentiation efficiency [18-20] of stem cells. Given the high complexity of AD pathobiology, multifunctional strategies that are capable of simultaneously managing multiple AD pathologies, including Aβ clearance and neural regeneration, are urgently needed. However, the development of such multifunctional therapies has yet to be achieved. Here, we report a multifunctional NSC therapy that simultaneously improves Aβ clearance and neural regeneration in an APPswe/PS1dE9 double transgenic mouse model (Figure 1). Alzheimer's disease (AD) is a common dementia that is currently incurable. The existing treatments can only moderately relieve the symptoms of AD to slow down its progress. How to achieve effective neural regeneration to ameliorate cognitive impairments is a major challenge for current AD treatment. Here, the therapeutic potential of a nanoformulation-mediated neural stem cell (NSC) therapy capable of simultaneous Aβ clearance and neural regeneration is investigated in a murine model. Genetically engineered NSCs capable of stably and continuously expressing neprilysin (NEP) are developed to enhance Aβ degradation and NSC survival in the brain. A PBAE-PLGA-Ag 2 S-RA-siSOX9 (PPAR-siSOX9)...

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“…A very inspiring study used MIL-100 (Fe) as a drug carrier for siSOX9 and retinoic acid in combination with co-encapsulated ceria based nanozymes to reduce oxidative stress (Yu et al, 2020). This complex drug formulation was incubated with neuronal stem cells (NSCs) isolated from newborn mice prior to NSC transplantation at sites of lesions.…”

Section: Mofs For Neuronal Tissue Engineering and Implantsmentioning

confidence: 99%

Metal-Organic Framework (MOF)-Based Biomaterials for Tissue Engineering and Regenerative Medicine

Shyngys

Ren

Xiao-qi

et al. 2021

Front. Bioeng. Biotechnol.

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The synthesis of Metal-organic Frameworks (MOFs) and their evaluation for various applications is one of the largest research areas within materials sciences and chemistry. Here, the use of MOFs in biomaterials and implants is summarized as narrative review addressing primarely the Tissue Engineering and Regenerative Medicine (TERM) community. Focus is given on MOFs as bioactive component to aid tissue engineering and to augment clinically established or future therapies in regenerative medicine. A summary of synthesis methods suitable for TERM laboratories and key properties of MOFs relevant to biomaterials is provided. The use of MOFs is categorized according to their targeted organ (bone, cardio-vascular, skin and nervous tissue) and whether the MOFs are used as intrinsically bioactive material or as drug delivery vehicle. Further distinction between in vitro and in vivo studies provides a clear assessment of literature on the current progress of MOF based biomaterials. Although the present review is narrative in nature, systematic literature analysis has been performed, allowing a concise overview of this emerging research direction till the point of writing. While a number of excellent studies have been published, future studies will need to clearly highlight the safety and added value of MOFs compared to established materials for clinical TERM applications. The scope of the present review is clearly delimited from the general ‘biomedical application’ of MOFs that focuses mainly on drug delivery or diagnostic applications not involving aspects of tissue healing or better implant integration.

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MOF-encapsulated nanozyme enhanced siRNA combo: Control neural stem cell differentiation and ameliorate cognitive impairments in Alzheimer's disease model

Cited by 150 publications

References 63 publications

Bio-inspired chiral self-assemblies promoted neuronal differentiation of retinal progenitor cells through activation of metabolic pathway

Bio-inspired chiral self-assemblies promoted neuronal differentiation of retinal progenitor cells through activation of metabolic pathway

A Nanoformulation‐Mediated Multifunctional Stem Cell Therapy with Improved Beta‐Amyloid Clearance and Neural Regeneration for Alzheimer's Disease

Metal-Organic Framework (MOF)-Based Biomaterials for Tissue Engineering and Regenerative Medicine

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