Trabecular meshwork mesenchymal stem cell transplantation improve motor symptoms of parkinsonian rat model

Mostafavi, Hossein; Ghassemifard, Leila; Rostami, Ali; Alipour, Mohsen; Nadri, Samad

doi:10.1016/j.biologicals.2019.06.006

Cited by 19 publications

(11 citation statements)

References 40 publications

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“…AD‐MSCs and BM‐MSCs were isolated by our colleague, Arefian, and his group who showed their differentiation potentials towards different lineages such as osteo, adipo, and chondrogenic stem cells 16 . TM‐MSCs have been isolated and characterized by Nadri's group for their multipotency 15,17 . In the present study, we have also further characterized the isolated TM‐MSCs, AD‐MSCs, and BM‐MSCs for mesenchymal and hematopoietic CD markers by using flow cytometry.…”

Section: Resultsmentioning

confidence: 66%

“…16 TM-MSCs have been isolated and characterized by Nadri's group for their multipotency. 15,17 In the present study, we have also further characterized the isolated TM-MSCs, AD-MSCs, and BM-MSCs for mesenchymal and hematopoietic CD markers by using flow cytometry. All the three cell types were positive for CD73, CD90, and CD105, but negative for those of the haematopoetic stem cell markers, CD34 and CD45 (Figures 1-3).…”

Section: Mscs Characterizationmentioning

confidence: 89%

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Wnt/β‐catenin signaling pathway is involved in early dopaminergic differentiation of trabecular meshwork‐derived mesenchymal stem cells

Tafreshi

Arefian

Roussa

2022

J of Cellular Biochemistry

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Permanent degeneration and loss of dopaminergic (DA) neurons in substantia nigra is the main cause of Parkinson's disease. Considering the therapeutic application of stem cells in neurodegeneration, we sought to examine the neurogenic differentiation potential of the newly introduced neural crest originated mesenchymal stem cells (MSCs), namely, trabecular meshworkderived mesenchymal stem cells (TM-MSCs) compared to two other sources of MSCs, adipose tissue-derived stem cells (ADSCs) and bone marrow-derived mesenchymal stem cells (BM-MSCs). The three types of cells were therefore cultured in the presence and absence of a neural induction medium followed by the analysis of their differentiation potentials. Our results showed that TM-MSCs exhibited enhanced neural morphologies as well as higher expressions of MAP2 as the general neuron marker and Nurr-1 as an early DA marker compared to the adipose tissue-derived mesenchymal stem cells (AD-MSCs) and bone marrow-derived stem cells (BMSCs). Also, analysis of Nurr-1 immunostaining showed more intense Nurr-1 stained nuclei in the neurally induced TM-MSCs compared to those in the AD-MSCs, BMSCs, and noninduced control TM-MSCs. To examine if Wnt/beta-catenin pathway drives TM-MSCs towards a DA fate, we treated them with the Wnt agonist (CHIR, 3 μM) and the Wnt antagonist (IWP-2, 3 μM). Our results showed that the expressions of Nurr-1 and MAP2, as well as the Wnt/beta-catenin target genes, c-Myc and Cyclin D1, were significantly increased in the CHIR-treated TM-MSCs, but significantly reduced in those treated with IWP-2. Altogether, we declare first a higher neural potency of TM-MSCs compared to the more commonly used MSCs, BMSCs and ADSCs, and second that Wnt/beta-catenin activation directs the neurally induced TM-MSCs towards a DA fate.

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Section: Resultsmentioning

confidence: 66%

Section: Mscs Characterizationmentioning

confidence: 89%

Wnt/β‐catenin signaling pathway is involved in early dopaminergic differentiation of trabecular meshwork‐derived mesenchymal stem cells

Tafreshi

Arefian

Roussa

2022

J of Cellular Biochemistry

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“…A study by Mostafavi et al (2019) evaluated using MSCs in rat model of PD, where green fluorescent protein (GFP)-labeled MSCs were transplanted in brains of rats (in the striatum specifically). The study results showed an improvement in motor functions of PD rats after MSCs transplantation and an increasing in cells expressing tyrosine hydroxylase, which catalyzes the formation of L-dopa.…”

Section: Using Mscs In the Treatment Of Other Neurodegenerative Diseasesmentioning

confidence: 99%

Mesenchymal Stem Cell-Based Therapy for Lysosomal Storage Diseases and Other Neurodegenerative Disorders

et al. 2022

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Lysosomal storage diseases (LSDs) are a group of approximately 50 genetic disorders caused by mutations in genes coding enzymes that are involved in cell degradation and transferring lipids and other macromolecules. Accumulation of lipids and other macromolecules in lysosomes leads to the destruction of affected cells. Although the clinical manifestations of different LSDs vary greatly, more than half of LSDs have symptoms of central nervous system neurodegeneration, and within each disorder there is a considerable variation, ranging from severe, infantile-onset forms to attenuated adult-onset disease, sometimes with distinct clinical features. To date, treatment options for this group of diseases remain limited, which highlights the need for further development of innovative therapeutic approaches, that can not only improve the patients’ quality of life, but also provide full recovery for them. In many LSDs stem cell-based therapy showed promising results in preclinical researches. This review discusses using mesenchymal stem cells for different LSDs therapy and other neurodegenerative diseases and their possible limitations.

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“…Next, the number of rotations to the opposite side of the lesion (left) was calculated for all rats using the rotameter following intraperitoneal injection of 1 mg/kg of the apomorphine hydrochloride. We have conducted this test on day 0 (two weeks after Parkinson's induction and just before cell transplantation), 14 (two weeks after cell transplantation), 28 (four weeks after cell transplantation), and 42 (eight weeks after cell transplantation) (Figure 1B) (Mostafavi et al, 2019). Data were expressed in the form of a complete body rotation every minute as the following equation:…”

Section: -7-rotation Testmentioning

confidence: 99%

Neuroprotective Effects of Microfluidic Encapsulated Induced Conjunctival Mesenchymal Stem Cells Through Autophagy Modulation in a Parkinsonian Model

Mostafavi

Forouzandeh

Bigdeli

et al. 2021

Preprint

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Background and Aim: Parkinson's disease (PD) is a progressive neurodegenerative disorder in which cause is attributed to the alpha-synuclein (α-Syn) accumulation due to the decreases rated of autophagy. According to recent studies, cell therapy has been attracted much attention for PD treatment. Due to the many advantages mesenchymal stem cells (MSCs) have proposed, they have been considered a valuable resource for PD cell therapy. The present study aimed to investigate the therapeutic effect of Conjunctival MSCs (CJ-MSCs) on the autophagy manner and the expression of Mammalian target of rapamycin (mTOR), TH, and α-Syn in the parkinsonian rat model.Materials and Methods: our investigation has been performed using the Parkinson's model of rats. Stereotaxic 6-hydroxy dopamine (6-OHDA) was injected directly into the medial forebrain bundle (MFB) to induce Parkinson's disease. An apomorphine-induced rotation test was used to confirm the model establishment. CJ-MSCs were encapsulated in alginate microgel using a microfluidic system. The green fluorescent protein (GFP) labeled CJ-MSCs both encapsulated and free cells were transplanted into the rats' right striatum. Behavioral and molecular analyses have been carried out to evaluate the potency of CJ-MSCs (both encapsulated and free cells) on PD rats. The Rotation, Rotarod Open field test was recruited as the behavioral tests. Immunohistochemistry was used to determine the tyrosine hydroxylase (TH), and Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) has been performed for investigating the α-Syn and mTOR gene expression.Results: Our obtained results indicated that transplantation of CJ-MSCs leads to a decrease in the number of rotations while raising the balance and motor abilities. Immunohistochemistry analysis revealed an increase in the number of TH+ cells compared to the control group. The gene expression evaluation showed a significant reduction in mTOR and α-Syn mRNA levels than the control group. Our results also represented a significant difference between rats receiving encapsulated CJ-MSCs compared to the group received free CJ-MSCs.Conclusion: It seems that CJ-MSCs can promote the degradation of intracellular α-Syn by reducing mTOR and thus increase TH expression that led improve the motor functions of rats. Our results indicated the CJ-MSCs as a suitable source of MSCs to reduce PD complications.

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Trabecular meshwork mesenchymal stem cell transplantation improve motor symptoms of parkinsonian rat model

Cited by 19 publications

References 40 publications

Wnt/β‐catenin signaling pathway is involved in early dopaminergic differentiation of trabecular meshwork‐derived mesenchymal stem cells

Wnt/β‐catenin signaling pathway is involved in early dopaminergic differentiation of trabecular meshwork‐derived mesenchymal stem cells

Mesenchymal Stem Cell-Based Therapy for Lysosomal Storage Diseases and Other Neurodegenerative Disorders

Neuroprotective Effects of Microfluidic Encapsulated Induced Conjunctival Mesenchymal Stem Cells Through Autophagy Modulation in a Parkinsonian Model

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