scholarly journals 3D Bioprinting Mesenchymal Stem Cell-Derived Neural Tissues Using a Fibrin-Based Bioink

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1250
Author(s):  
Milena Restan Perez ◽  
Ruchi Sharma ◽  
Nadia Zeina Masri ◽  
Stephanie Michelle Willerth
Keyword(s):  
Stem Cells ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Disease Modeling ◽  
3D Bioprinting ◽  
Fibroblast Growth ◽  
Class Iii ◽  
Fibroblast Growth Factor 8 ◽  
Neural Tissues ◽  
Fibroblast Growth Factor Basic

Current treatments for neurodegenerative diseases aim to alleviate the symptoms experienced by patients; however, these treatments do not cure the disease nor prevent further degeneration. Improvements in current disease-modeling and drug-development practices could accelerate effective treatments for neurological diseases. To that end, 3D bioprinting has gained significant attention for engineering tissues in a rapid and reproducible fashion. Additionally, using patient-derived stem cells, which can be reprogrammed to neural-like cells, could generate personalized neural tissues. Here, adipose tissue-derived mesenchymal stem cells (MSCs) were bioprinted using a fibrin-based bioink and the microfluidic RX1 bioprinter. These tissues were cultured for 12 days in the presence of SB431542 (SB), LDN-193189 (LDN), purmorphamine (puro), fibroblast growth factor 8 (FGF8), fibroblast growth factor-basic (bFGF), and brain-derived neurotrophic factor (BDNF) to induce differentiation to dopaminergic neurons (DN). The constructs were analyzed for expression of neural markers, dopamine release, and electrophysiological activity. The cells expressed DN-specific and early neuronal markers (tyrosine hydroxylase (TH) and class III beta-tubulin (TUJ1), respectively) after 12 days of differentiation. Additionally, the tissues exhibited immature electrical signaling after treatment with potassium chloride (KCl). Overall, this work shows the potential of bioprinting engineered neural tissues from patient-derived MSCs, which could serve as an important tool for personalized disease models and drug-screening.

scholarly journals Therapeutic effect of TO901317 on 6-OHDA-induced Parkinson rats in vitro and in vivo

2020 ◽  
Author(s):  
Miaomiao Li ◽  
Junqing Yang ◽  
Oumei Cheng ◽  
Zhe Peng ◽  
Yin Luo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Stem Cells ◽  
Parkinson's Disease ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Dopamine Neurons ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Fibroblast Growth ◽  
Fibroblast Growth Factor 8

Abstract Background: Stem cells from different sources could differentiate into dopamine-producing cells and ameliorate behavioral deficits in Parkinsonian models. Especially, human bone marrow mesenchymal stem cells (hBMSCs) have many advantages without ethical dispute. Liver X receptor s (LXRs) are involved in the maintenance of the normal function of the central nervous system myelin. We have reported the induction of cocktail-induced da phenotypes from adult rat BMSCs by using sonic hedgehog (SHH), fibroblast growth factor 8 (FGF8), basic fibroblast growth factor (bFGF) and TO901317 (agonist of LXRs) with 87.42% of efficiency in 6 days of period of induction. But the previous work did not verify whether the induced cells had the corresponding neural function. Methods: In this study, we demonstrated that TO901317 could promote the differentiation of hBMSCs into dopaminergic neurons. Neuronal markers (Tuj1, Neun and Nestin), dopamine neuron markers (tyrosine hydroxylase, TH), LXRa and LXRb were detected by immunofluorescence. RT-qPCR was used to measure the mRNA expressions of adenosine triphosphate-binding cassette transporter A1 (ABCA1). Western Blotting detected the changes of LXRa, LXRb and TH expression. Results: TO901317 significantly enhanced the differentiation from hBMSCs to DA neurons. Only the LXR+GF group released dopamine by the result of enzyme linked immunosorbent assay (ELISA). Compared with the control group and GF group, the optimal time for differentiation of hBMSCs treated by 0.5mM TO901317 combined with GF was six days. And the maximum induction efficiency was 91.67%. After transplanting induced-cells into Parkinson's disease rats, the symptoms of Parkinson's rats decreased, and the number of dopamine neurons increased in the substantia nigra and striatum. Conclusions: TO901317 promoted differentiation of hBMSCs into dopamine neurons may be related to activation of LXR-ABCA1 signaling pathway. These data suggest that TO901317 may serve as a potential therapeutic methods for Parkinson's disease.

scholarly journals The Efficacy of Graphene Foams for Culturing Mesenchymal Stem Cells and Their Differentiation into Dopaminergic Neurons

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Nishat Tasnim ◽  
Vikram Thakur ◽  
Munmun Chattopadhyay ◽  
Binata Joddar
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Stem Cell Differentiation ◽  
Fibroblast Growth ◽  
Collagen Gels ◽  
3D Graphene ◽  
Fibroblast Growth Factor Basic ◽  
Graphene Foams

The implantation of stem cells in vivo is the ideal approach for the restoration of normal life functions, such as replenishing the decreasing levels of affected dopaminergic (DA) neurons during neurodegenerative disease conditions. However, combining stem cells with biomaterial scaffolds provides a promising strategy for engineering tissues or cellular delivery for directed stem cell differentiation as a means of replacing diseased/damaged tissues. In this study, mouse mesenchymal stem cells (MSCs) were differentiated into DA neurons using sonic hedgehog, fibroblast growth factor, basic fibroblast growth factor, and brain-derived neurotrophic factor, while they were cultured within collagen-coated 3D graphene foams (GF). The differentiation into DA neurons within the collagen-coated GF and controls (collagen gels, plastic) was confirmed using β-III tubulin, tyrosine hydroxylase (TH), and NeuN positive immunostaining. Enhanced expression of β-III tubulin, TH, and NeuN and an increase in the average neurite extension length were observed when cells were differentiated within collagen-coated GF in comparison with collagen gels. Furthermore, these graphene-based scaffolds were not cytotoxic as MSC seemed to retain viability and proliferated substantially during in vitro culture. In summary, these results suggest the utility of 3D graphene foams towards the differentiation of DA neurons from MSC, which is an important step for neural tissue engineering applications.

scholarly journals Therapeutic effect of TO901317 on 6-OHDA-induced Parkinson rats in vitro and in vivo

2020 ◽  
Author(s):  
Miaomiao Li ◽  
Junqing Yang ◽  
Oumei Cheng ◽  
Zhe Peng ◽  
Yin Luo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Stem Cells ◽  
Parkinson's Disease ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Dopamine Neurons ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Fibroblast Growth ◽  
Fibroblast Growth Factor 8

Abstract Background: Stem cells from different sources could differentiate into dopamine-producing cells and ameliorate behavioral deficits in Parkinsonian models. Especially, human bone marrow mesenchymal stem cells (hBMSCs) have many advantages without ethical dispute. Liver X receptor s (LXRs) are involved in the maintenance of the normal function of the central nervous system myelin. We have reported the induction of cocktail-induced da phenotypes from adult rat BMSCs by using sonic hedgehog (SHH), fibroblast growth factor 8 (FGF8), basic fibroblast growth factor (bFGF) and TO901317 (agonist of LXRs) with 87.42% of efficiency in 6 days of period of induction. But the previous work did not verify whether the induced cells had the corresponding neural function. Methods: In this study, we demonstrated that TO901317 could promote the differentiation of hBMSCs into dopaminergic neurons. Neuronal markers (Tuj1, Neun and Nestin), dopamine neuron markers (tyrosine hydroxylase, TH), LXRa and LXRb were detected by immunofluorescence. RT-qPCR was used to measure the mRNA expressions of adenosine triphosphate-binding cassette transporter A1 (ABCA1). Western Blotting detected the changes of LXRa, LXRb and TH expression. Results: TO901317 significantly enhanced the differentiation from hBMSCs to DA neurons. Only the LXR+GF group released dopamine by the result of enzyme linked immunosorbent assay (ELISA). Compared with the control group and GF group, the optimal time for differentiation of hBMSCs treated by 0.5mM TO901317 combined with GF was six days. And the maximum induction efficiency was 91.67%. After transplanting induced-cells into Parkinson's disease rats, the symptoms of Parkinson's rats decreased, and the number of dopamine neurons increased in the substantia nigra and striatum. Conclusions: TO901317 promoted differentiation of hBMSCs into dopamine neurons may be related to activation of LXR-ABCA1 signaling pathway. These data suggest that TO901317 may serve as a potential therapeutic methods for Parkinson's disease.

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