RNAi-mediated silencing of HLA A2 suppressed acute rejection against human fibroblast xenografts in the striatum of 6-OHDA lesioned rats

Liang, Caixia; Xu, Yuesheng; Zheng, Dong; Sun, Xiaohong; Xu, Qunyuan; Duan, Deyi

doi:10.1016/j.jneuroim.2016.05.002

Cited by 5 publications

(3 citation statements)

References 39 publications

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“…Indeed, both xenogeneic fibroblasts and ECM can trigger the immune system. [26][27][28][29] Another option would be to study the human construct in immunosuppressed animal and/or primate models but these can be very limited by animal size, Figure 7. Ascorbate, insulin or growth factor supplementation did not increase human or ovine sheet perforation force.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, both xenogeneic fibroblasts and ECM can trigger the immune system. 26–29 Another option would be to study the human construct in immunosuppressed animal and/or primate models but these can be very limited by animal size, costs, and ethical concerns. Finally, one can endeavor to recreate the construct using cells from a relevant animal model.…”

Section: Discussionmentioning

confidence: 99%

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Cell-assembled extracellular matrix (CAM) sheet production: Translation from using human to large animal cells

et al. 2021

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We have created entirely biological tissue-engineered vascular grafts (TEVGs) using sheets of cell-assembled extracellular matrix (CAM) produced by human fibroblasts in vitro. A large animal TEVG would allow long-term pre-clinical studies in a clinically relevant setting (graft size and allogeneic setting). Therefore, canine, porcine, ovine, and human skin fibroblasts were compared for their ability to form CAM sheets. Serum sourcing greatly influenced CAM production in a species-dependent manner. Ovine cells produced the most homogenous and strongest animal CAM sheets but remained ≈3-fold weaker than human sheets despite variations of serum, ascorbate, insulin, or growth factor supplementations. Key differences in cell growth dynamics, tissue development, and tissue architecture and composition were observed between human and ovine. This study demonstrates critical species-to-species differences in fibroblast behavior and how they pose a challenge when attempting to substitute animal cells for human cells during the development of tissue-engineered constructs that require long-term cultures.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cell-assembled extracellular matrix (CAM) sheet production: Translation from using human to large animal cells

et al. 2021

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“…Thus, 6-OHDA-induced lesions are the most widely used animal models of PD. [15][16][17] There is currently no cure for PD. Medication (levodopa, dopamine agonists, and monoamine oxidase B inhibitors) and surgery (deep brain stimulation) only relieve and delay the symptoms.…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective Effects of Betulin in Pharmacological and Transgenic Caenorhabditis elegans Models of Parkinson’s Disease

Tsai

Liu

et al. 2017

Cell Transplant

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Parkinson’s disease (PD) is the second most common degenerative disorder of the central nervous system in the elderly. It is characterized by progressive loss of dopaminergic neurons in the substantia nigra pars compacta, as well as by motor dysfunction. Although the causes of PD are not well understood, aggregation of α-synuclein (α-syn) in neurons contributes to this disease. Current therapeutics for PD provides satisfactory symptom relief but not a cure. Treatment strategies include attempts to identify new drugs that will prevent or arrest the progressive course of PD by correcting disease-specific pathogenic process. Betulin is derived from the bark of birch trees and possesses anticancer, antimicrobial, and anti-inflammatory properties. The aim of the present study was to evaluate the potential for betulin to ameliorate PD features in Caenorhabditis elegans (C. elegans) models. We demonstrated that betulin diminished α-syn accumulation in the transgenic C. elegans model. Betulin also reduced 6-hydroxydopamine-induced dopaminergic neuron degeneration, reduced food-sensing behavioral abnormalities, and reversed life-span decreases in a pharmacological C. elegans model. Moreover, we found that the enhancement of proteasomes activity by promoting rpn1 expression and downregulation of the apoptosis pathway gene, egl-1, may be the molecular mechanism for betulin-mediated protection against PD pathology. Together, these findings support betulin as a possible treatment for PD and encourage further investigations of betulin as an antineurodegenerative agent.

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The NLRP3 Inflammasome is Involved in the Pathogenesis of Parkinson’s Disease in Rats

et al. 2017

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The etiology and pathogenesis of Parkinson's disease (PD) are complicated and have not been fully elucidated, but an important association has been identified between inflammation and PD. In this study, we investigated the role of the nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain-containing (NLRP) 3 inflammasome, consisting of NLRP3, caspase-1 and cytokines of the IL-1 family, in lipopolysaccharide (LPS)-induced and 6-hydroxydopamine (6-OHDA)-induced PD rats. Microinjection of different doses of caspase-1 inhibitor (Ac-YVAD-CMK, 300 or 1200 ng/rat) was performed for seven consecutive days. Then, rotational behavior, the number of dopamine (DA) neurons in the substantia nigra pars compacta (SNc), and the mRNA and protein expression levels of NLRP3 inflammasome components were measured 14 days after the microinjection setup was established. Results showed that high mRNA and protein expression levels of NLRP3 inflammasome components were observed in the injected side of the LPS- and 6-OHDA-induced PD rats; Ac-YVAD-CMK inhibited the mRNA and protein expression of NLRP3 inflammasome components in both LPS- and 6-OHDA-induced PD rats. Moreover, the number of rotations was significantly decreased, and the number of DA neurons in the SNc improved. Our data indicate that the NLRP3 inflammasome participates in the pathogenesis of PD and that inhibiting the downstream pathway of the NLRP3/caspase-1/IL-1β axis can alleviate the occurrence of PD symptoms, providing a new basis for the prevention and treatment of PD.

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RNAi-mediated silencing of HLA A2 suppressed acute rejection against human fibroblast xenografts in the striatum of 6-OHDA lesioned rats

Cited by 5 publications

References 39 publications

Cell-assembled extracellular matrix (CAM) sheet production: Translation from using human to large animal cells

Cell-assembled extracellular matrix (CAM) sheet production: Translation from using human to large animal cells

Neuroprotective Effects of Betulin in Pharmacological and Transgenic Caenorhabditis elegans Models of Parkinson’s Disease

The NLRP3 Inflammasome is Involved in the Pathogenesis of Parkinson’s Disease in Rats

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