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Rahmani S, Nadri S, Eskandari M, Mostafavi H. Encapsulation of trabecular meshwork mesenchymal stem cell using microfluidic system for differentiation into neuron-like cells. Int J Artif Organs 2025:3913988251333280. [PMID: 40296219 DOI: 10.1177/03913988251333280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/30/2025]
Abstract
OBJECTIVE Neurodegenerative diseases are a class of nervous system disorders characterized by progressive neuronal degeneration and loss of function. Among emerging therapeutic approaches, microfluidic-enabled stem cell encapsulation and transplantation has gained recognition as a promising strategy for mitigating neuronal damage. In this work, human mesenchymal stem cells (MSCs), isolated from trabecular meshwork (TM) tissue, were successfully encapsulated and differentiated into neural-like cells via a microfluidic platform to demonstrate their potential for neural repair applications. MATERIALS AND METHODS The isolated mesenchymal stem cells were cultured on a microfluidic system (fabricated by soft lithography methods) and treated with medium containing DMEM supplemented with RA, IBMX, and forskolin for 7 days. Quantitative PCR (qPCR) were used to analyze differentiated TM-MSC and their expression of neural-like specific markers such as Nestin and b-tubulin 3. RESULTS qPCR analysis revealed the presence of genes characteristic of neural cells (Nestin and β-tubulin 3) in cells differentiated both within a microfluidic system and on traditional tissue culture plates (TCPS). qPCR result showed that cells on 1.5% alginate showed higher expression of β-tubulin 3 compared to those on 1% alginate, 2% alginate, and TCPS (p < 0.0001). In contrast, Nestin expression showed no statistically significant differences across all pairwise comparisons (p > 0.05 for all groups). CONCLUSION The findings indicate that mesenchymal stem cells derived from the trabecular meshwork (TM-MSCs) may serve as promising candidates for cell-based therapeutic strategies. Furthermore, the microfluidic platform implemented in this study exhibits potential utility as a delivery vehicle for TM-MSCs in therapeutic interventions targeting neurological disorders.
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Affiliation(s)
- Sina Rahmani
- Student Research Committee, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
- Department of Physiology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Samad Nadri
- Zanjan Pharmaceutical Nanotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
- Zanjan Metabolic Diseases Research Center, Health and Metabolic Diseases Research Institute, Zanjan University of Medical Sciences, Zanjan, Iran
- Department of Medical Nanotechnology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Mehdi Eskandari
- Department of Physiology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Hossein Mostafavi
- Department of Physiology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
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An W, Zhang W, Qi J, Xu W, Long Y, Qin H, Yao K. Mesenchymal stem cells and mesenchymal stem cell-derived exosomes: a promising strategy for treating retinal degenerative diseases. Mol Med 2025; 31:75. [PMID: 39984849 PMCID: PMC11846226 DOI: 10.1186/s10020-025-01120-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2024] [Accepted: 02/07/2025] [Indexed: 02/23/2025] Open
Abstract
Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic strategy in regenerative medicine, demonstrating significant potential for clinical applications. Evidence suggests that MSCs not only exhibit multipotent differentiation potential but also exert critical therapeutic effects in retinal degenerative diseases via robust paracrine mechanisms. MSCs protect retinal cells from degenerative damage by modulating inflammation, inhibiting apoptosis, alleviating oxidative stress, and suppressing cell death pathways. Furthermore, MSCs contribute to retinal structural and functional stability by facilitating vascular remodeling and donating mitochondria to retinal cells. Of particular interest, MSC-derived exosomes have gained widespread attention as a compelling cell-free therapy. Owing to their potent anti-inflammatory, anti-apoptotic, and vascular-stabilizing properties, exosomes show significant promise for the treatment of retinal degenerative diseases.
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Affiliation(s)
- Wenjing An
- Institute of Visual Neuroscience and Stem Cell Engineering, Wuhan University of Science and Technology, Wuhan, 430065, China
- College of Life Sciences and Health, Wuhan University of Science and Technology, Wuhan, 430065, China
| | - Wenliang Zhang
- Institute of Visual Neuroscience and Stem Cell Engineering, Wuhan University of Science and Technology, Wuhan, 430065, China
- College of Life Sciences and Health, Wuhan University of Science and Technology, Wuhan, 430065, China
| | - Jia Qi
- Institute of Visual Neuroscience and Stem Cell Engineering, Wuhan University of Science and Technology, Wuhan, 430065, China
- College of Life Sciences and Health, Wuhan University of Science and Technology, Wuhan, 430065, China
| | - Weihui Xu
- Institute of Visual Neuroscience and Stem Cell Engineering, Wuhan University of Science and Technology, Wuhan, 430065, China
- College of Life Sciences and Health, Wuhan University of Science and Technology, Wuhan, 430065, China
| | - Yushan Long
- Institute of Visual Neuroscience and Stem Cell Engineering, Wuhan University of Science and Technology, Wuhan, 430065, China
- College of Life Sciences and Health, Wuhan University of Science and Technology, Wuhan, 430065, China
| | - Huan Qin
- Institute of Visual Neuroscience and Stem Cell Engineering, Wuhan University of Science and Technology, Wuhan, 430065, China.
- College of Life Sciences and Health, Wuhan University of Science and Technology, Wuhan, 430065, China.
| | - Kai Yao
- Institute of Visual Neuroscience and Stem Cell Engineering, Wuhan University of Science and Technology, Wuhan, 430065, China.
- College of Life Sciences and Health, Wuhan University of Science and Technology, Wuhan, 430065, China.
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Xiao Y, McGhee CNJ, Zhang J. Adult stem cells in the eye: Identification, characterisation, and therapeutic application in ocular regeneration - A review. Clin Exp Ophthalmol 2024; 52:148-166. [PMID: 38214071 DOI: 10.1111/ceo.14309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Accepted: 09/25/2023] [Indexed: 01/13/2024]
Abstract
Adult stem cells, present in various parts of the human body, are undifferentiated cells that can proliferate and differentiate to replace dying cells within tissues. Stem cells have specifically been identified in the cornea, trabecular meshwork, crystalline lens, iris, ciliary body, retina, choroid, sclera, conjunctiva, eyelid, lacrimal gland, and orbital fat. The identification of ocular stem cells broadens the potential therapeutic strategies for untreatable eye diseases. Currently, stem cell transplantation for corneal and conjunctival diseases remains the most common stem cell-based therapy in ocular clinical management. Lens epithelial stem cells have been applied in the treatment of paediatric cataracts. Several early-phase clinical trials for corneal and retinal regeneration using ocular stem cells are also underway. Extensive preclinical studies using ocular stem cells have been conducted, showing encouraging outcomes. Ocular stem cells currently demonstrate great promise in potential treatments of eye diseases. In this review, we focus on the identification, characterisation, and therapeutic application of adult stem cells in the eye.
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Affiliation(s)
- Yuting Xiao
- Department of Ophthalmology, New Zealand National Eye Centre, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
| | - Charles N J McGhee
- Department of Ophthalmology, New Zealand National Eye Centre, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
| | - Jie Zhang
- Department of Ophthalmology, New Zealand National Eye Centre, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
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Yang H, Li Z, Jin W, Yang A. Application progress of human amniotic membrane in vitreoretinopathy: a literature review. Front Med (Lausanne) 2023; 10:1206577. [PMID: 37881631 PMCID: PMC10597697 DOI: 10.3389/fmed.2023.1206577] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2023] [Accepted: 09/19/2023] [Indexed: 10/27/2023] Open
Abstract
Recently, the application of the amniotic membrane (AM) in ophthalmology is gradually expanding from the anterior to the posterior segment of the eye. Its characteristics of anti-inflammation, anti-bacterial, anti-vascularization, immune regulation, anti-fibrosis, pro-epithelialization, and so forth have made it a hot topic in ophthalmic research. AM has been confirmed to repair photoreceptors, restore normal retinal structures, and close the abnormal structures in the optic disc. Currently, the application areas mainly include retinal hole, retinal detachment, optic disc pit, retinal degenerative diseases, and choroidal hole. This article reviews the current literature applying AM transplantation in the treatment of various posterior segment diseases while comparing the clinical outcomes with other techniques.
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Affiliation(s)
- Huawei Yang
- Eye Center, Renmin Hospital of Wuhan University, Wuhan, China
| | - Ziyue Li
- Eye Center, Renmin Hospital of Wuhan University, Wuhan, China
- First Clinical College, Wuhan University, Wuhan, China
| | - Wei Jin
- Eye Center, Renmin Hospital of Wuhan University, Wuhan, China
| | - Anhuai Yang
- Eye Center, Renmin Hospital of Wuhan University, Wuhan, China
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Dolatyar B, Zeynali B, Shabani I, Parvaneh Tafreshi A. High-efficient serum-free differentiation of trabecular meshwork mesenchymal stem cells into Schwann-like cells on polylactide electrospun nanofibrous scaffolds. Neurosci Lett 2023; 813:137417. [PMID: 37549866 DOI: 10.1016/j.neulet.2023.137417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2023] [Revised: 07/14/2023] [Accepted: 08/02/2023] [Indexed: 08/09/2023]
Abstract
Cell-based therapies of the peripheral nerve injury (PNI) have provided satisfactory outcomes among which Schwann cells (SCs) are the most reliable candidate to improve repair of the damaged nerve, however, it is difficult to obtain sufficient amount of SCs for clinical applications. Trabecular meshwork-derived mesenchymal stem cells (TM-MSCs) are newly introduced neural crest originated MSCs, which may have a desirable potential for Schwann-like differentiation due to their common lineage. On the other hand, one of the challenges of cell-based therapies is usage of serum containing media which is inappropriate for clinical applications. In the present study, we investigated the differentiation potential of TM-MSCs into Schwann-like cells on polylactide (PLA) nanofibrous scaffolds in the presence or absence of serum. Our results revealed that PLA nanofibers had no negative effects on the cell growth and proliferation of TM-MSCs, and improved Schwann-like differentiation compared with tissue culture plates (TCPs). More importantly, when the cells cultured on the scaffold in the presence of serum-free media (SFM), expression mRNA levels of SC markers (S100B, GAP43, GFAP and SOX10) were significantly increased compared with those of serum-rich groups. Immunostaining of TM-MSCs cultured on serum-free PLA nanofibrous scaffolds also showed significant expression of GAP43, GFAP and SOX10 compared to those of control, indicating the efficient role of SFM in the differentiation of TM-MSCs into SCs lineage. Overall, the findings of this study revealed the differentiation potential of TM-MSCs to SC fate for the first time, and also showed the beneficial effects of SFM and PLA nanofibrous scaffolds as a promising approach for peripheral nerve regeneration.
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Affiliation(s)
- Banafsheh Dolatyar
- Developmental Biology Lab, School of Biology, College of Science, University of Tehran, Tehran, Iran
| | - Bahman Zeynali
- Developmental Biology Lab, School of Biology, College of Science, University of Tehran, Tehran, Iran.
| | - Iman Shabani
- Department of Biomedical Engineering, Amirkabir University of Technology, Tehran, Iran
| | - Azita Parvaneh Tafreshi
- Department of Molecular Medicine, Faculty of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
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Mohammadi P, Nadri S, Abdanipour A, Mortazavi Y. Microchip encapsulation and microRNA-7 overexpression of trabecular meshwork mesenchymal stem/stromal cells improve motor function after spinal cord injury. J Biomed Mater Res A 2023; 111:1482-1494. [PMID: 37042544 DOI: 10.1002/jbm.a.37549] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2022] [Revised: 03/24/2023] [Accepted: 04/04/2023] [Indexed: 04/13/2023]
Abstract
Manipulation of stem cells and microencapsulation through microfluidic chips has shown more promising results in treating complex conditions, such as spinal cord injury (SCI), than traditional treatments. This study aimed to investigate the potency of neural differentiation and its therapeutic role in SCI animal model of trabecular meshwork mesenchymal stem/stromal cells (TMMSCs) via miR-7 overexpression and microchip-encapsulated. TMMSCs are transduced with miR-7 via a lentiviral vector (TMMSCs-miR-7[+]) and encapsulated in alginate-reduced graphene oxide (alginate-rGO) hydrogel via a microfluidic chip. Neuronal differentiation of transduced cells in hydrogel (3D) and tissue cultures plate (2D) was assessed by expressing specific mRNAs and proteins. Further evaluation is being carried out through 3D and 2D TMMSCs-miR-7(+ and -) transplantation into the rat contusion SCI model. TMMSCs-miR-7(+) encapsulated in the microfluidic chip (miR-7-3D) increased nestin, β-tubulin III, and MAP-2 expression compared with 2D culture. Moreover, miR-7-3D could improve locomotor behavior in contusion SCI rats, decrease cavity size, and increase myelination. Our results revealed that miR-7 and alginate-rGO hydrogel were involved in the neuronal differentiation of TMMSCs in a time-dependent manner. In addition, the microfluidic-encapsulated miR-7 overexpression TMMSCs represented a better survival and integration of the transplanted cells and the repair of SCI. Collectively, the combination of miR-7 overexpression and encapsulation of TMMSCs in hydrogels may represent a promising new treatment for SCI.
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Affiliation(s)
- Parvin Mohammadi
- Student Research Committee, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
- Department of Medical Biotechnology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Samad Nadri
- Zanjan Metabolic Diseases Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
- Department of Medical Nanotechnology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
- Zanjan Pharmaceutical Nanotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Alireza Abdanipour
- Department of Anatomy, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Yousef Mortazavi
- Department of Medical Biotechnology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
- Cancer Gene Therapy Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
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Feng P, Wang W, Xu W, Cao Q, Zhu W. Application of a Magnetic Platform in α6 Integrin-Positive iPSC-TM Purification. Bioengineering (Basel) 2023; 10:bioengineering10040410. [PMID: 37106597 PMCID: PMC10135729 DOI: 10.3390/bioengineering10040410] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Accepted: 03/24/2023] [Indexed: 03/29/2023] Open
Abstract
The emergence of induced pluripotent stem cell (iPSC) technology has provided a new approach to regenerating decellularized trabecular meshwork (TM) in glaucoma. We have previously generated iPSC-derived TM (iPSC-TM) using a medium conditioned by TM cells and verified its function in tissue regeneration. Because of the heterogeneity of iPSCs and the isolated TM cells, iPSC-TM cells appear to be heterogeneous, which impedes our understanding of how the decellularized TM may be regenerated. Herein, we developed a protocol based on a magnetic-activated cell sorting (MACS) system or an immunopanning (IP) method for sorting integrin subunit alpha 6 (ITGA6)-positive iPSC-TM, an example of the iPSC-TM subpopulation. We first analyzed the purification efficiency of these two approaches by flow cytometry. In addition, we also determined cell viability by analyzing the morphologies of the purified cells. To conclude, the MACS-based purification could yield a higher ratio of ITGA6-positive iPSC-TM and maintain a relatively higher cell viability than the IP-based method, allowing for the preparation of any iPSC-TM subpopulation of interest and facilitating a better understanding of the regenerative mechanism of iPSC-based therapy.
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Affiliation(s)
- Pengchao Feng
- Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao 266021, China
| | - Wenyan Wang
- Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao 266021, China
| | - Wenhua Xu
- Institute of Regenerative Medicine and Laboratory Technology Innovation, Qingdao University, Qingdao 266021, China
| | - Qilong Cao
- Qingdao Haier Biotech Co., Ltd., Qingdao 266109, China
- Correspondence: (Q.C.); (W.Z.)
| | - Wei Zhu
- Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao 266021, China
- Advanced Innovation Center for Big Data-Based Precision Medicine, Beijing University of Aeronautics and Astronautics-Capital Medical University, Beijing 100083, China
- Correspondence: (Q.C.); (W.Z.)
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8
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Coulon SJ, Schuman JS, Du Y, Bahrani Fard MR, Ethier CR, Stamer WD. A novel glaucoma approach: Stem cell regeneration of the trabecular meshwork. Prog Retin Eye Res 2022; 90:101063. [PMID: 35398015 PMCID: PMC9464663 DOI: 10.1016/j.preteyeres.2022.101063] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2021] [Revised: 03/20/2022] [Accepted: 03/24/2022] [Indexed: 12/13/2022]
Abstract
Glaucoma is the leading cause of global irreversible blindness, necessitating research for new, more efficacious treatment options than currently exist. Trabecular meshwork (TM) cells play an important role in the maintenance and function of the aqueous outflow pathway, and studies have found that there is decreased cellularity of the TM in glaucoma. Regeneration of the TM with stem cells has been proposed as a novel therapeutic option by several reports over the last few decades. Stem cells have the capacity for self-renewal and the potential to differentiate into adult functional cells. Several types of stem cells have been investigated in ocular regenerative medicine: tissue specific stem cells, embryonic stem cells, induced pluripotent stem cells, and adult mesenchymal stem cells. These cells have been used in various glaucoma animal models and ex vivo models and have shown success in IOP homeostasis and TM cellularity restoration. They have also demonstrated stability without serious side effects for a significant period of time. Based on current knowledge of TM pathology in glaucoma and existing literature regarding stem cell regeneration of this tissue, we propose a human clinical study as the next step in understanding this potentially revolutionary treatment paradigm. The ability to protect and replace TM cells in glaucomatous eyes could change the field forever.
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Affiliation(s)
- Sara J Coulon
- Department of Ophthalmology, NYU Grossman School of Medicine, NYU Langone Health, New York University, New York, NY, USA
| | - Joel S Schuman
- Department of Ophthalmology, NYU Grossman School of Medicine, NYU Langone Health, New York University, New York, NY, USA; Center for Neural Science, College of Arts and Science, New York University, New York, NY, USA; Departments of Biomedical Engineering and Electrical and Computer Engineering, New York University Tandon School of Engineering, Brooklyn, NY, USA; Department of Physiology and Neuroscience, NYU Grossman School of Medicine, NYU Langone Health, New York University, New York, NY, USA.
| | - Yiqin Du
- Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Mohammad Reza Bahrani Fard
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University School of Medicine, Atlanta, GA, USA
| | - C Ross Ethier
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University School of Medicine, Atlanta, GA, USA
| | - W Daniel Stamer
- Departments of Ophthalmology and Biomedical Engineering, Duke University, Durham, NC, USA
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Rizkiawan DE, Evelyn M, Tjandra KC, Setiawan B. Utilization of Modified Induced Pluripotent Stem Cells as the Advance Therapy of Glaucoma: A Systematic Review. Clin Ophthalmol 2022; 16:2851-2859. [PMID: 36061629 PMCID: PMC9439642 DOI: 10.2147/opth.s372114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Accepted: 08/22/2022] [Indexed: 11/23/2022] Open
Abstract
Glaucoma is an optic neuropathy disease that causes cupping of the optic disc and decreased visual field. Glaucoma is still the second leading cause of blindness globally, with a worldwide prevalence of more than 76 million people in 2020. However, no therapy can cure glaucoma completely, especially when optic nerve damage has occurred. Available treatments only play a role in keeping the intraocular pressure stable This research aims to determine the potential use of modified stem cell therapy to treat intraocular damage in glaucoma cases. Literature research was conducted by involving seven online databases, namely Pubmed, ScienceDirect®, Proquest, EBSCOhost®, SAGE®, Clinicalkey®, and Scopus, published between 2010–2020 with the keywords stem cells; therapy; glaucoma; optic nerve. Six articles were selected, and out of the six articles, all writings were experimental research. The entire literature states that modified stem cell therapy has the potential as a therapeutic option in treating intraocular damage in patients with glaucoma. Based on the systematic literature review that has been carried out, it is known that stem cell therapy has the potential to be a therapeutic option in treating glaucoma cases. Much more research is needed to assess the effectiveness of modified stem cell therapy in managing intraocular damage due to glaucoma.
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Affiliation(s)
| | - Malinda Evelyn
- Faculty of Medicine, Diponegoro University, Semarang, Central Java, Indonesia
| | | | - Budi Setiawan
- Department of Internal Medicine, Diponegoro University, Semarang, Central Java, Indonesia
- Correspondence: Budi Setiawan, Department of Internal Medicine, Diponegoro University, Jl. Badak Raya 74, Kota Semarang, Central Java, Indonesia, 50167, Tel +6285865118118, Fax +622467412115, Email
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Sahebdel F, Parvaneh Tafreshi A, Arefian E, Roussa E, Nadri S, Zeynali B. A Wnt/β-catenin signaling pathway is involved in early dopaminergic differentiation of trabecular meshwork-derived mesenchymal stem cells. J Cell Biochem 2022; 123:1120-1129. [PMID: 35533251 DOI: 10.1002/jcb.30269] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Revised: 04/20/2022] [Accepted: 04/22/2022] [Indexed: 01/08/2023]
Abstract
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 meshwork-derived 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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Affiliation(s)
- Faezeh Sahebdel
- Developmental Biology Laboratory, Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran
| | - Azita Parvaneh Tafreshi
- Developmental Biology Laboratory, Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran.,Department of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
| | - Ehsan Arefian
- Department of Microbiology, School of Biology, College of Science, University of Tehran, Tehran, Iran
| | - Eleni Roussa
- Department of Molecular Embryology, Faculty of Medicine, Institute of Anatomy and Cell Biology, Albert Ludwigs University Freiburg, Freiburg, Germany
| | - Samad Nadri
- Department of Medical Nanotechnology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Bahman Zeynali
- Developmental Biology Laboratory, Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran
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Chiang MC, Chern E. Current Development, Obstacle and Futural Direction of Induced Pluripotent Stem Cell and Mesenchymal Stem Cell Treatment in Degenerative Retinal Disease. Int J Mol Sci 2022; 23:ijms23052529. [PMID: 35269671 PMCID: PMC8910526 DOI: 10.3390/ijms23052529] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 02/20/2022] [Accepted: 02/23/2022] [Indexed: 11/26/2022] Open
Abstract
Degenerative retinal disease is one of the major causes of vision loss around the world. The past several decades have witnessed emerging development of stem cell treatment for retinal disease. Nevertheless, sourcing stem cells remains controversial due to ethical concerns and their rarity. Furthermore, induced pluripotent stem cells (iPSCs) and mesenchymal stem cells (MSCs) are both isolated from patients’ mature tissues; thus, issues such as avoiding moral controversy and adverse events related to immunosuppression and obtaining a large number of cells have opened a new era in regenerative medicine. This review focuses on the current application and development, clinical trials, and latest research of stem cell therapy, as well as its limitations and future directions.
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Stem cell transplantation as a progressing treatment for retinitis pigmentosa. Cell Tissue Res 2022; 387:177-205. [PMID: 35001210 DOI: 10.1007/s00441-021-03551-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Accepted: 10/27/2021] [Indexed: 11/02/2022]
Abstract
Retinal degenerative diseases such as retinitis pigmentosa (RP) are of the major causes of vision loss in developed countries. Despite the unclear pathophysiology, treatment methods have been investigated vastly in the past decades. This review article mainly discusses the advances in application of stem cell and progenitor transplantation for retinitis pigmentosa. Stem cell sources such as mesenchymal stem cells, embryonic stem cells, induced pluripotent stem cells, neural stem cells, retinal progenitor cells, and olfactory ensheathing cells are discussed separately in addition to a brief description of two approaches for treatment of early-stage RP, including gene therapy and nutritional therapy.
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Savoj S, Esfahani MHN, Karimi A, Karamali F. Integrated stem cells from apical papilla in a 3D culture system improve human embryonic stem cell derived retinal organoid formation. Life Sci 2022; 291:120273. [PMID: 35016877 DOI: 10.1016/j.lfs.2021.120273] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Revised: 12/15/2021] [Accepted: 12/23/2021] [Indexed: 01/08/2023]
Abstract
AIM Eye organoids are 3D models of the retina that provide new possibilities for studying retinal development, drug toxicity and the molecular mechanisms of diseases. Although there are several protocols that can be used to generate functional tissues, none have been used to assemble human retinal organoids containing mesenchymal stem cells (MSCs). MAIN METHODS In this study we intend to assess the effective interactions of MSCs and human embryonic stem cells (hESCs) during retinal organoid formation. We evaluated the inducing activities of bone marrow MSCs (BM-MSCs), trabecular meshwork (TM), and stem cells from apical papilla (SCAP)-derived MSCs in differentiation of hESCs in a three-dimensional (3D) direct co-culture system. KEY FINDINGS In comparison with the two other MSC sources, the induction potential of SCAP was confirmed in the co-culture system. Although the different SCAP cell ratios did not show any significant morphology changes during the first seven days, increasing the number of SCAPs improved formation of the optic vesicle (OV) structure, which was confirmed by assessment of specific markers. The OVs subsequently developed to an optic cup (OC), which was similar to the in vivo environment. These arrangements expressed MITF in the outer layer and CHX10 in the inner layer. SIGNIFICANCE We assessed the inducing activity of SCAP during differentiation of hESCs towards a retinal fate in a 3D organoid system. However, future studies be conducted to gather additional details about the development of the eye field, retinal differentiation, and the molecular mechanisms of diseases.
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Affiliation(s)
- Soraya Savoj
- Department of Biology, University of Payam Noor, Isfahan, Iran; Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
| | - Mohammad Hossein Nasr Esfahani
- Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
| | - Akbar Karimi
- Department of Biology, University of Payam Noor, Isfahan, Iran.
| | - Fereshteh Karamali
- Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
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14
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Forouzandeh M, Bigdeli MR, Mostafavi H, Nadri S, Eskandari M. Therapeutic potentials of human microfluidic encapsulated conjunctival mesenchymal stem cells on the rat model of Parkinson's disease. Exp Mol Pathol 2021; 123:104703. [PMID: 34619140 DOI: 10.1016/j.yexmp.2021.104703] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2021] [Revised: 09/22/2021] [Accepted: 10/02/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIM Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by the destruction of the dopaminergic neurons in the nigrostriatal pathway, leading to motor-behavioral complications. Cell therapy has been proposed as a promising approach for PD treatment using various cellular sources. Despite a few disadvantages mesenchymal stem cells (MSCs) represent, they have more auspicious effects for PD cell therapy. The present study aimed to evaluate a new source of MSCs isolated from human Conjunctiva (CJ-MSCs) impact on PD complications for the first time. MATERIALS AND METHODS Parkinson's was induced by stereotactic injection of 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle (MFB). An apomorphine-induced rotation test was used to confirm the model establishment. After PD model confirmation, green fluorescent protein (GFP) labeled CJ-MSCs and induced CJ-MSCs (microfluidic encapsulated and non-capsulated) were transplanted into the rats' right striatum. Then Rotation, Rotarod, and Open-field tests were performed to evaluate the behavioral assessment. Additionally, the immunohistochemistry technique was used for identifying tyrosine hydroxylase (TH). RESULTS According to the obtained data, the cell transplantation caused a reduction in the rats' rotation number and improved locomotion compared to the control group. The previous results were also more pronounced in induced and microfluidic encapsulated cells compared to other cells. Rats recipient CJ-MSCs also have represented more TH-expressed GFP-labeled cell numbers in the striatum than the control group. CONCLUSION It can be concluded that CJ-MSCs therapy can have protective effects against PD complications and nerve induction of cells due to their ability to express dopamine. On the other hand, CJ-MSCs microencapsulating leads to enhance even more protective effect of CJ-MSCs. However, confirmation of this hypothesis requires further studies and investigation of these cells' possible mechanisms of action.
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Affiliation(s)
| | - Mohammad Reza Bigdeli
- Faculty of Life Sciences, Shahid-Beheshti University, Tehran, Iran; Inistitute for Cognitive and Brain Science, Shahid Beheshti University, Tehran, Iran.
| | - Hossein Mostafavi
- Department of Physiology, School of Medicine, Zanjan University of Medical Science, Zanjan, Iran..
| | - Samad Nadri
- Department of Medical Nanotechnology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Mehdi Eskandari
- Department of Physiology, School of Medicine, Zanjan University of Medical Science, Zanjan, Iran
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15
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Fan X, Bilir EK, Kingston OA, Oldershaw RA, Kearns VR, Willoughby CE, Sheridan CM. Replacement of the Trabecular Meshwork Cells-A Way Ahead in IOP Control? Biomolecules 2021; 11:biom11091371. [PMID: 34572584 PMCID: PMC8464777 DOI: 10.3390/biom11091371] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Revised: 09/09/2021] [Accepted: 09/13/2021] [Indexed: 12/11/2022] Open
Abstract
Glaucoma is one of the leading causes of vision loss worldwide, characterised with irreversible optic nerve damage and progressive vision loss. Primary open-angle glaucoma (POAG) is a subset of glaucoma, characterised by normal anterior chamber angle and raised intraocular pressure (IOP). Reducing IOP is the main modifiable factor in the treatment of POAG, and the trabecular meshwork (TM) is the primary site of aqueous humour outflow (AH) and the resistance to outflow. The structure and the composition of the TM are key to its function in regulating AH outflow. Dysfunction and loss of the TM cells found in the natural ageing process and more so in POAG can cause abnormal extracellular matrix (ECM) accumulation, increased TM stiffness, and increased IOP. Therefore, repair or regeneration of TM's structure and function is considered as a potential treatment for POAG. Cell transplantation is an attractive option to repopulate the TM cells in POAG, but to develop a cell replacement approach, various challenges are still to be addressed. The choice of cell replacement covers autologous or allogenic approaches, which led to investigations into TM progenitor cells, induced pluripotent stem cells (iPSCs), and mesenchymal stem cells (MSCs) as potential stem cell source candidates. However, the potential plasticity and the lack of definitive cell markers for the progenitor and the TM cell population compound the biological challenge. Morphological and differential gene expression of TM cells located within different regions of the TM may give rise to different cell replacement or regenerative approaches. As such, this review describes the different approaches taken to date investigating different cell sources and their differing cell isolation and differentiation methodologies. In addition, we highlighted how these approaches were evaluated in different animal and ex vivo model systems and the potential of these methods in future POAG treatment.
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Affiliation(s)
- Xiaochen Fan
- Department of Eye and Vision Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L69 3BX, UK; (X.F.); (E.K.B.); (O.A.K.); (V.R.K.)
| | - Emine K. Bilir
- Department of Eye and Vision Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L69 3BX, UK; (X.F.); (E.K.B.); (O.A.K.); (V.R.K.)
| | - Olivia A. Kingston
- Department of Eye and Vision Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L69 3BX, UK; (X.F.); (E.K.B.); (O.A.K.); (V.R.K.)
| | - Rachel A. Oldershaw
- Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L69 3BX, UK;
| | - Victoria R. Kearns
- Department of Eye and Vision Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L69 3BX, UK; (X.F.); (E.K.B.); (O.A.K.); (V.R.K.)
| | - Colin E. Willoughby
- Department of Eye and Vision Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L69 3BX, UK; (X.F.); (E.K.B.); (O.A.K.); (V.R.K.)
- Genomic Medicine, Biomedical Sciences Research Institute, Ulster University, Coleraine BT52 1SA, UK
- Correspondence: (C.E.W.); (C.M.S.); Tel.: +44-(28)-701-2338 (C.E.W.); +44-(151)-794-9031 (C.M.S.)
| | - Carl M. Sheridan
- Department of Eye and Vision Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L69 3BX, UK; (X.F.); (E.K.B.); (O.A.K.); (V.R.K.)
- Correspondence: (C.E.W.); (C.M.S.); Tel.: +44-(28)-701-2338 (C.E.W.); +44-(151)-794-9031 (C.M.S.)
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16
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Xiong S, Xu Y, Wang Y, Kumar A, Peters DM, Du Y. α5β1 Integrin Promotes Anchoring and Integration of Transplanted Stem Cells to the Trabecular Meshwork in the Eye for Regeneration. Stem Cells Dev 2020; 29:290-300. [PMID: 31854234 DOI: 10.1089/scd.2019.0254] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Stem cell-based therapy to restore the function of abnormal trabecular meshwork (TM) and decrease intraocular pressure (IOP) provides a novel approach to treat open-angle glaucoma. However, molecular mechanism for stem cells homing and anchoring to the TM remains unclear. This study aimed to discover the function of integrins in homing and integration of exogenous TM stem cells (TMSCs) to the TM. Integrin expression in TMSCs and fibroblasts was evaluated by quantitative real-time PCR (qPCR), flow cytometry, immunofluorescent staining, and western blotting. Expression of integrin ligand fibronectin was detected in cultured TM cells and murine TM tissue by immunostaining. Cell affinity to TM cells or fibronectin matrix was examined to compare TMSCs with TMSCs functionally blocked with an α5β1 integrin antibody. TMSCs and TMSCs with α5β1 integrin-blocking were intracamerally injected into wild-type mice. Wholemounts and cryosections were analyzed to discover cell distribution and integration at 3 days and 1 month. IOP was measured to detect possible changes. We discovered that human TMSCs expressed a higher level of α5β1 integrin than fibroblasts, but similar levels of αvβ3 and αvβ5 integrin. Upregulation of fibronectin was found in both TM cells treated with dexamethasone for 14 days and murine TM tissues damaged by laser photocoagulation. TMSCs were able to attach to the TM cells and fibronectin matrix in vitro. When the surface α5β1 integrin was blocked, the attached cell numbers were significantly reduced. Both TMSCs and TMSCs incubated with an α5β1 integrin-blocking antibody could home to the mouse TM after injection. TMSCs blocked with the α5β1 integrin-blocking antibody were not retained in the TM tissue at 1 month. The injected cells did not affect mouse IOP. In conclusion, highly expressed α5β1 integrin participates in maintaining TMSCs anchored and integrated to the TM, which would be crucial for stem cell-based therapy for glaucoma.
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Affiliation(s)
- Siqi Xiong
- Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China.,Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Yi Xu
- Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Yiwen Wang
- Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China.,Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Ajay Kumar
- Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Donna M Peters
- Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Yiqin Du
- Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania.,Department of Developmental Biology, University of Pittsburgh, Pittsburgh, Pennsylvania.,McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
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17
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Kumar A, Xu Y, Du Y. Stem Cells from Human Trabecular Meshwork Hold the Potential to Develop into Ocular and Non-Ocular Lineages After Long-Term Storage. Stem Cells Dev 2020; 29:49-61. [PMID: 31680626 PMCID: PMC6931915 DOI: 10.1089/scd.2019.0169] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2019] [Accepted: 11/01/2019] [Indexed: 01/10/2023] Open
Abstract
Stem cells from the eye hold a great potential for vision restoration and can also be used for regeneration in other tissues. In this study, we characterized the stem cell properties of Trabecular meshwork stem cells (TMSCs) after long-term cryopreservation (∼8 years). TMSCs derived from four donors were examined for their viability and proliferation, as well as stem cell marker expression. Spheroid formation, colony formation, and multipotency were investigated. We observed that TMSCs were fully viable with variable proliferation ability. They expressed the stem cell markers CD90, CD166, CD105, CD73, OCT4, SSEA4, Notch1, KLF4, ABCG2, Nestin, and HNK1 detected by flow cytometry, quantitative polymerase chain reaction, or immunofluorescent staining. They could form spheroids and colonies after thawing. All TMSCs were able to differentiate into osteocytes, neural cells, and trabecular meshwork (TM) cells, but not adipocytes. Differentiated TM cells responded to dexamethasone treatment with increased expression of myocilin and angiopoietin-like 7 (ANGPTL7). In a nutshell, our study demonstrated that TMSCs retain their stem cell properties after long-term cryopreservation and hence can be an effective cell therapy source for various clinical applications.
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Affiliation(s)
- Ajay Kumar
- Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Yi Xu
- Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Yiqin Du
- Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania
- Department of Developmental Biology, University of Pittsburgh, Pittsburgh, Pennsylvania
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
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18
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Jedari B, Rahmani A, Naderi M, Nadri S. MicroRNA‐7 promotes neural differentiation of trabecular meshwork mesenchymal stem cell on nanofibrous scaffold. J Cell Biochem 2019; 121:2818-2827. [DOI: 10.1002/jcb.29513] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2019] [Accepted: 10/08/2019] [Indexed: 01/22/2023]
Affiliation(s)
- Behrouz Jedari
- Department of Medical BiotechnologyZanjan University of Medical SciencesZanjan Iran
| | - Ali Rahmani
- Department of Medical NanotechnologyZanjan University of Medical SciencesZanjan Iran
| | - Mahmood Naderi
- Cell‐Based Therapies Research Center, Digestive Disease Research InstituteTehran University of Medical SciencesTehran Iran
| | - Samad Nadri
- Department of Medical NanotechnologyZanjan University of Medical SciencesZanjan Iran
- Zanjan Metabolic Diseases Research CenterZanjan University of Medical SciencesZanjan Iran
- Zanjan Pharmaceutical Nanotechnology Research CenterZanjan University of Medical SciencesZanjan Iran
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19
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Nekouian S, Sojoodi M, Nadri S. Fabrication of conductive fibrous scaffold for photoreceptor differentiation of mesenchymal stem cell. J Cell Physiol 2019; 234:15800-15808. [PMID: 30714142 DOI: 10.1002/jcp.28238] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2018] [Revised: 11/23/2018] [Accepted: 11/30/2018] [Indexed: 01/24/2023]
Abstract
Conductive nanofibrous scaffolds with that can conduct electrical current have a great potential in neural tissue engineering. The purpose of this study was to survey effects of electrical stimulation and polycaprolactone/polypyrrole/multiwall carbon nanotube (PCL/PPY/MWCNTs) fibrous scaffold on photoreceptor differentiation of trabecular meshwork mesenchymal stem cells (TM-MSCs). PCL/PPY/MWCNTs scaffold was made by electrospinning method. TM-MSCs were seeded on PCL/PPY/MWCNTs scaffold and stimulated with a potential of 115 V/m. Scanning electron microscopy, transmission electron microscopy, and FT-IR were used to evaluate the fabricated scaffold. Immunofluorescence and quantitative real-time polymerase chain reaction were used to examine differentiated cells. Scanning electron microscopy, transmitting electron microscopy, and FT-IR confirmed the creation of the composite structure of fibers. RT-qPCR analysis showed that the expression of rhodopsin and peripherin genes in electrically stimulated cells were significantly higher (5.7- and 6.23-fold, respectively; p ≤ 0.05) than those with no electrical stimulation. Collectively, it seems that the combination of PCL/PPY/MWCNTs scaffold, as a suitable conductive scaffold, and electrical stimulation could be an effective approach in the differentiation of stem cells in retinal tissue engineering.
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Affiliation(s)
- Soraya Nekouian
- Department of Medical Nanotechnology, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Mahdi Sojoodi
- Department of Electrical and Computer Engineering, Tarbiat Modares University, Tehran, Iran
| | - Samad Nadri
- Department of Medical Nanotechnology, Zanjan University of Medical Sciences, Zanjan, Iran.,Zanjan Metabolic Diseases Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.,Zanjan Pharmaceutical Nanotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
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20
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Mirfazeli ES, Arefian E, Nadri S, Rezazadeh Valojerdi R, Kehtari M, Zeynali B. DKK1 expression is suppressed by miR-9 during induced dopaminergic differentiation of human trabecular meshwork mesenchymal stem cells. Neurosci Lett 2019; 707:134250. [DOI: 10.1016/j.neulet.2019.05.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2019] [Accepted: 05/03/2019] [Indexed: 12/11/2022]
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21
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Trabecular meshwork mesenchymal stem cell transplantation improve motor symptoms of parkinsonian rat model. Biologicals 2019; 61:61-67. [PMID: 31262640 DOI: 10.1016/j.biologicals.2019.06.006] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2018] [Revised: 03/21/2019] [Accepted: 06/26/2019] [Indexed: 01/26/2023] Open
Abstract
Stem cell transplantation is a new therapeutic strategy in the treatment of neurodegenerative disorders such as Parkinson's disease (PD). Therefore, in this study, the therapeutic effects of Trabecular Meshwork Mesenchymal Stem Cells (TM-MSCs) transplantation, as a new source of mesenchymal stem cells, were evaluated in the animal model of PD. After the development and confirmation of hemi-parkinsonian rats by administration of 6-hydroxy dopamine (6-OHDA) and apomorphine-induced rotation test, green fluorescent protein (GFP) labeled TM-MSCs (normal and induced cells) were transplanted in the striatum of rats. Next, the rotation test, rotarod test, open field, passive avoidance memory tests and immunohistochemistry for tyrosine hydroxylase (TH) were done. The results showed that the number of turns significantly decreased and the improvement of motor performance was achieved after cell transplantation. However, there was no significant difference in passive avoidance memory of animals documented by shuttle box test. The number of GFP- labeled cells expressing TH significantly is increased compared to the vehicle group. Collectively, it seems that TM-MSCs and induced TM-MSCs cell transplantation have positive effects on some aspects of the animal model of PD. Other studies may reveal the potentially positive aspects of these cells in the laboratory and clinical studies.
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22
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Ding SLS, Koh AEH, Kumar S, Ali Khan MS, Alzahrani B, Mok PL. Genetically-modified human mesenchymal stem cells to express erythropoietin enhances differentiation into retinal photoreceptors: An in-vitro study. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY 2019; 195:33-38. [PMID: 31060031 DOI: 10.1016/j.jphotobiol.2019.04.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/13/2018] [Revised: 04/12/2019] [Accepted: 04/23/2019] [Indexed: 12/12/2022]
Abstract
Dysfunctional or death of retinal photoreceptors is an irreversible phenomenon that is closely associated with a broad range of retinal degenerative diseases, such as retinitis pigmentosa and age-related macular degeneration (AMD), resulting in successive loss of visual function and blindness. In search for viable treatment for retinal degenerative diseases, mesenchymal stem cells (MSCs) has demonstrated promising therapeutic capabilities to repair and replace damaged photoreceptor cells in both in vitro and in vivo conditions. Nevertheless, the dearth of MSC differentiation capacity into photoreceptors has limited its use in cell replacement therapy. Erythropoietin (EPO) has vital role in early neural retinal cell differentiation and demonstrated rescue potential on dying photoreceptor cells. Hence, we aimed to evaluate the differentiation capacity of MSCs into photoreceptor cells in the presence of human EPO protein. We derived the MSC from human Wharton's jelly of umbilical cord and transduced the cells with lentivirus particles encoding EPO and green fluorescent protein (GFP) as reporter gene. The transduced cells were selectively cultured and induced to differentiate into photoreceptors by exposing to photoreceptor differentiation cocktail. Our preliminary results showed that transduced cells exposed to induction medium had an enhanced differentiation capacity when compared to non-transduced cells. Our results demonstrated a novel strategy to increase the yield of in vitro photoreceptor differentiation and may be potentially useful in improving the efficiency of stem cell transplantation for ocular disorders.
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Affiliation(s)
- Suet Lee Shirley Ding
- Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
| | - Avin Ee-Hwan Koh
- Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
| | - Suresh Kumar
- Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia; Genetics and Regenerative Medicine Research Centre, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia; Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
| | - Mohammed Safwan Ali Khan
- Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia; Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, Texas A&M University, College Station, TX 77843, USA
| | - Badr Alzahrani
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, P.O. Box 2014, Aljouf Province, Saudi Arabia.
| | - Pooi Ling Mok
- Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia; Genetics and Regenerative Medicine Research Centre, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, P.O. Box 2014, Aljouf Province, Saudi Arabia.
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23
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Castro A, Du Y. Trabecular Meshwork Regeneration - A Potential Treatment for Glaucoma. CURRENT OPHTHALMOLOGY REPORTS 2019; 7:80-88. [PMID: 31316866 DOI: 10.1007/s40135-019-00203-2] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Purpose In this review, we overview the pathophysiology of primary open-angle glaucoma as it relates to the trabecular meshwork (TM), exploring modes of TM dysfunction and regeneration via stem cell therapies. Recent Findings Stem cells from a variety of sources, including trabecular meshwork, mesenchymal, adipose and induced pluripotent stem cells, have shown the potential to differentiate into TM cells in vitro or in vivo and to regenerate the TM in vivo, lowering intraocular pressure (IOP) and reducing glaucomatous retinal ganglion cell damage. Summary Stem cell therapies for TM regeneration provide a robust and promising suite of treatments for eventual lowering of IOP and prevention of glaucomatous vision loss in humans in the future. Further investigation into stem cell homing mechanisms and the safety of introducing these cells into human anterior chamber, for instance, are required before clinical applications in treating glaucoma patients.
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Affiliation(s)
- Alexander Castro
- Department of Ophthalmology, University of Pittsburgh, Pittsburgh, PA 15213.,University of Virginia, Charlottesville, VA 22904
| | - Yiqin Du
- Department of Ophthalmology, University of Pittsburgh, Pittsburgh, PA 15213.,McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15213.,Department of Developmental Biology, University of Pittsburgh, Pittsburgh, PA 15213
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24
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Ding SSL, Subbiah SK, Khan MSA, Farhana A, Mok PL. Empowering Mesenchymal Stem Cells for Ocular Degenerative Disorders. Int J Mol Sci 2019; 20:E1784. [PMID: 30974904 PMCID: PMC6480671 DOI: 10.3390/ijms20071784] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Revised: 03/13/2019] [Accepted: 03/13/2019] [Indexed: 12/24/2022] Open
Abstract
Multipotent mesenchymal stem cells (MSCs) have been employed in numerous pre-clinical and clinical settings for various diseases. MSCs have been used in treating degenerative disorders pertaining to the eye, for example, age-related macular degeneration, glaucoma, retinitis pigmentosa, diabetic retinopathy, and optic neuritis. Despite the known therapeutic role and mechanisms of MSCs, low cell precision towards the targeted area and cell survivability at tissue needing repair often resulted in a disparity in therapeutic outcomes. In this review, we will discuss the current and feasible strategy options to enhance treatment outcomes with MSC therapy. We will review the application of various types of biomaterials and advances in nanotechnology, which have been employed on MSCs to augment cellular function and differentiation for improving treatment of visual functions. In addition, several modes of gene delivery into MSCs and the types of associated therapeutic genes that are important for modulation of ocular tissue function and repair will be highlighted.
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Affiliation(s)
- Shirley Suet Lee Ding
- Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.
| | - Suresh Kumar Subbiah
- Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.
- Genetics and Regenerative Medicine Research Centre, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.
- Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.
| | - Mohammed Safwan Ali Khan
- Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.
- Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, Texas University, College Station, Texas 77843, USA.
| | - Aisha Farhana
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, P.O. Box 2014, Aljouf Province, Saudi Arabia.
| | - Pooi Ling Mok
- Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.
- Genetics and Regenerative Medicine Research Centre, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, P.O. Box 2014, Aljouf Province, Saudi Arabia.
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25
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Khalilifar MA, Baghaban Eslaminejad MR, Ghasemzadeh M, Hosseini S, Baharvand H. In Vitro and In Vivo Comparison of Different Types of Rabbit Mesenchymal Stem Cells for Cartilage Repair. CELL JOURNAL 2019; 21:150-160. [PMID: 30825288 PMCID: PMC6397606 DOI: 10.22074/cellj.2019.6149] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/03/2018] [Accepted: 09/08/2018] [Indexed: 01/09/2023]
Abstract
Objective Systematic studies indicate a growing number of clinical studies that use mesenchymal stem cells (MSCs) for the
treatment of cartilage lesions. The current experimental and preclinical study aims to comparatively evaluate the potential of
MSCs from a variety of tissues for the treatment of cartilage defect in rabbit’s knee which has not previously been reported.
Materials and Methods In this experimental study, MSCs isolated from bone marrow (BMMSCs), adipose (AMSCs), and ears
(EMSCs) of rabbits and expanded under in vitro culture. The growth rate and differentiation ability of MSCs into chondrocyte
and the formation of cartilage pellet were investigated by drawing the growth curve and real-time polymerase chain reaction
(RT-PCR), respectively. Then, the critical cartilage defect was created on the articular cartilage (AC) of the rabbit distal femur,
and MSCs in collagen carrier were transplanted. The studied groups were as the control (only defect), sham (defect with
scaffold), BMMSCs in the scaffold, EMSCs in the scaffold, and EMSCs in the scaffold with cartilage pellets. Histological and
the gene expression analysis were performed following the transplantation.
Results Based on our comparative in vitro investigation, AMSCs possessed the highest growth rate, as well as the
lowest chondrogenic differentiation potential. In this context, MSCs of the ear showed a significantly higher growth rate
and cartilage differentiation potential than those of bone marrow tissue (P<0.05). According to our in vivo assessments,
BMMSC- and EMSC-seeded scaffolds efficiently improved the cartilage defect 4 weeks post-transplantation, while no
improvement was observed in the group contained the cartilage pellets.
Conclusion It seems that the ear contains MSCs that promote cartilage regeneration as much as the conventional MSCs
from the bone marrow. Considering a high proliferation rate and easy harvesting of MSCs of the ear, this finding could be of
value for the regenerative medicine.
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Affiliation(s)
- Mohammad Ali Khalilifar
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.,Department of Developmental Biology, University of Science and Culture, Tehran, Iran
| | - Mohamad Reza Baghaban Eslaminejad
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran. Electronic Address:
| | - Mohammad Ghasemzadeh
- Infertility and Reproductive Health Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Samaneh Hosseini
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Hossein Baharvand
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.,Department of Developmental Biology, University of Science and Culture, Tehran, Iran
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26
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Sun H, Zhu Q, Guo P, Zhang Y, Tighe S, Zhu Y. Trabecular meshwork cells are a valuable resource for cellular therapy of glaucoma. J Cell Mol Med 2019; 23:1678-1686. [PMID: 30659738 PMCID: PMC6378204 DOI: 10.1111/jcmm.14158] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2018] [Revised: 11/15/2018] [Accepted: 12/23/2018] [Indexed: 12/16/2022] Open
Abstract
Trabecular meshwork (TM) contains a subset of adult stem cells or progenitors that can be differentiated into corneal endothelial cells, adipocytes and chondrocytes, but not osteocytes or keratocytes. Accordingly, these progenitors can be utilized as a cell‐based therapy to prevent blindness caused by glaucoma, corneal endothelial dysfunction and other diseases in general. In this review, we review in vitro expansion techniques for TM progenitors, discuss their phenotypic properties, and highlight their potential clinical applications in various ophthalmic diseases.
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Affiliation(s)
- Hong Sun
- Department of Ophthalmology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Qin Zhu
- Department of Ophthalmology, the Second People's Hospital of Yunnan Province (Fourth Affiliated Hospital of Kunming Medical University), Yunnan Eye Institute, Key Laboratory of Yunnan Province for the Prevention and Treatment of Ophthalmology (2017DG008), Provincial Innovation Team for Cataract and Ocular Fundus Disease, The Second People's Hospital of Yunnan Province (2017HC010), Expert Workstation of Yao Ke (2017IC064), Kunming, China
| | - Ping Guo
- Shenzhen University School of Medicine, Shenzhen Eye Hospital, Shenzhen, China
| | - Yuan Zhang
- Tissue Tech, Inc., Ocular Surface Center, Ocular Surface Research & Education Foundation, Miami, Florida
| | - Sean Tighe
- Tissue Tech, Inc., Ocular Surface Center, Ocular Surface Research & Education Foundation, Miami, Florida
| | - Yingting Zhu
- Tissue Tech, Inc., Ocular Surface Center, Ocular Surface Research & Education Foundation, Miami, Florida
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27
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Human stem cells home to and repair laser-damaged trabecular meshwork in a mouse model. Commun Biol 2018; 1:216. [PMID: 30534608 PMCID: PMC6283842 DOI: 10.1038/s42003-018-0227-z] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2018] [Accepted: 11/14/2018] [Indexed: 12/13/2022] Open
Abstract
Glaucoma is the leading cause of irreversible vision loss, and reducing elevated intraocular pressure is currently the only effective clinical treatment. The trabecular meshwork is the main resistance site for aqueous outflow that maintains intraocular pressure. In this study, we transplanted human trabecular meshwork stem cells (TMSCs) intracamerally into mice that received laser photocoagulation over a 180° arc of the trabecular meshwork. TMSCs preferentially homed and integrated to the laser-damaged trabecular meshwork region and expressed differentiated cell markers at 2 and 4 weeks. Laser-induced inflammatory and fibrotic responses were prevented by TMSC transplantation with simultaneous ultrastructure and function restoration. Cell affinity and migration assays and elevated expression of CXCR4 and SDF1 in laser-treated mouse trabecular meshwork suggest that the CXCR4/SDF1 chemokine axis plays an important role in TMSC homing. Our results suggest that TMSCs may be a viable candidate for trabecular meshwork refunctionalization as a novel treatment for glaucoma. Hongmin Yun et al. show that implanted human stem cells can accurately home to and repair damaged trabecular meshwork tissue in the mouse eye via a chemokine axis defined by CXCR4 and SDF1. The study suggests that stem cells from the trabecular meshwork could be used to refunctionalize the outflow pathway as a treatment for glaucoma.
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28
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Barati G, Nadri S, Hajian R, Rahmani A, Mostafavi H, Mortazavi Y, Taromchi AH. Differentiation of microfluidic‐encapsulated trabecular meshwork mesenchymal stem cells into insulin producing cells and their impact on diabetic rats. J Cell Physiol 2018; 234:6801-6809. [DOI: 10.1002/jcp.27426] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2018] [Accepted: 08/22/2018] [Indexed: 12/12/2022]
Affiliation(s)
- Ghasem Barati
- Department of Medical Biotechnology and Nanotechnology School of Medicine, Zanjan University of Medical Sciences Zanjan Iran
| | - Samad Nadri
- Department of Medical Biotechnology and Nanotechnology School of Medicine, Zanjan University of Medical Sciences Zanjan Iran
- Zanjan Metabolic Diseases Research Center, Zanjan University of Medical Sciences Zanjan Iran
- Cancer Gene Therapy Research Center, Zanjan University of Medical Sciences Zanjan Iran
| | - Ramin Hajian
- Novel Fluidic Systems Pioneers Co., Innovation & Entrepreneurship Center of Amirkabir University of Technology Tehran Iran
| | - Ali Rahmani
- Department of Medical Biotechnology and Nanotechnology School of Medicine, Zanjan University of Medical Sciences Zanjan Iran
| | - Hossein Mostafavi
- Department of Physiology and Pharmacology School of Medicine, Zanjan University of Medical Sciences Zanjan Iran
| | - Yousef Mortazavi
- Department of Medical Biotechnology and Nanotechnology School of Medicine, Zanjan University of Medical Sciences Zanjan Iran
- Cancer Gene Therapy Research Center, Zanjan University of Medical Sciences Zanjan Iran
| | - Amir Hossein Taromchi
- Department of Medical Biotechnology and Nanotechnology School of Medicine, Zanjan University of Medical Sciences Zanjan Iran
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29
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Over-expression of CNTF in bone marrow mesenchymal stem cells protects RPE cells from short-wavelength, blue-light injury. In Vitro Cell Dev Biol Anim 2018; 54:355-365. [PMID: 29564604 DOI: 10.1007/s11626-018-0243-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2018] [Accepted: 03/13/2018] [Indexed: 12/20/2022]
Abstract
Increasing evidence has demonstrated that excessive blue-light (BL) with high photochemical energy and phototoxicity could induce apoptosis in retinal pigment epithelium (RPE) cells. RPE apoptosis leads to retina damage and further aggravate age-related macular degeneration (ARMD). Because of their neuroprotective, plasticity, and immunomodulatory ability, bone marrow mesenchymal stem cells (BMSCs) are recognized for retinal neuroprotection. RPE cells possess ciliary neurotrophic factor (CNTF) receptor complexes and can respond to CNTF; hence, we investigated the effects of BMSCs over-expressing CNTF on BL-injured RPE cells. BL-injured RPE cells were co-cultured with CNTF-BMSCs and GFP-BMSCs for 24 and 48 h. Superoxide dismutase and malondialdehyde assays were conducted to examine the effects of CNTF-BMSCs on the oxidative stress of RPE cells. VEGF protein secretion by RPE was determined by ELISA, and western blotting analysis was used to determine apoptotic protein expression and autophagic flux. Immunofluorescence was used to demonstrate the relationship between autophagy and apoptosis. We found that CNTF-BMSCs enhanced antioxidant capacity, decreased VEGF secretion, promoted autophagic flux, and inhibited apoptosis in BL-injured RPE cells, compared to GFP-BMSCs. Our findings suggest that CNTF over-expression enhances the protective effects of BMSCs on RPE cells, thus indicating subretinal-transplantation of CNTF-BMSCs may be a promising therapy for BL-injured retina.
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30
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Isolation and Expansion of Multipotent Progenitors from Human Trabecular Meshwork. Sci Rep 2018; 8:2814. [PMID: 29434243 PMCID: PMC5809375 DOI: 10.1038/s41598-018-21098-2] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2017] [Accepted: 01/30/2018] [Indexed: 12/13/2022] Open
Abstract
To expand multi-potent progenitors from human trabecular meshwork (TM), we have created a new optimized method on two-dimensional (2D) followed by three-dimensional (3D) Matrigel in modified embryonic stem cell medium supplemented with 5% fetal bovine serum (MESCM + 5% FBS). The expanded TM cells were small cuboidal cells expressing TM markers such as AQP1, MGP, CHI3L1, and AnkG, embryonic stem cell (ESC) markers such as Oct4, Sox2, Nanog, and ABCG2, and neural crest (NC) markers such as p75NTR, FOXD3, Sox9, Sox10, and MSX1. Although expanded cells lost expression of these markers after passage, the cells regained the markers when Passage 2 cells were seeded on 3D Matrigel through activation of canonical BMP signaling. Such restored progenitors could differentiate into corneal endothelial cells, adipocytes, and chondrocytes but not keratocytes or osteocytes. Therefore, we have concluded that human TM harbors multipotent progenitors that can be effectively isolated and expanded using 2D Matrigel in MESCM + 5% FBS. This unique in vitro model system can be used to understand how TM is altered in glaucoma and whether such TM progenitor cells might one day be used for treating glaucoma or corneal endothelial dysfunction.
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31
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Thakur A, Mishra S, Pena J, Zhou J, Redenti S, Majeska R, Vazquez M. Collective adhesion and displacement of retinal progenitor cells upon extracellular matrix substrates of transplantable biomaterials. J Tissue Eng 2018; 9:2041731417751286. [PMID: 29344334 PMCID: PMC5764132 DOI: 10.1177/2041731417751286] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2017] [Accepted: 12/07/2017] [Indexed: 12/11/2022] Open
Abstract
Strategies to replace retinal photoreceptors lost to damage or disease rely upon the migration of replacement cells transplanted into sub-retinal spaces. A significant obstacle to the advancement of cell transplantation for retinal repair is the limited migration of transplanted cells into host retina. In this work, we examine the adhesion and displacement responses of retinal progenitor cells on extracellular matrix substrates found in retina as well as widely used in the design and preparation of transplantable scaffolds. The data illustrate that retinal progenitor cells exhibit unique adhesive and displacement dynamics in response to poly-l-lysine, fibronectin, laminin, hyaluronic acid, and Matrigel. These findings suggest that transplantable biomaterials can be designed to improve cell integration by incorporating extracellular matrix substrates that affect the migratory behaviors of replacement cells.
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Affiliation(s)
- Ankush Thakur
- Department of Biomedical Engineering, The City College of New York, New York, NY, USA
| | - Shawn Mishra
- Department of Biomedical Engineering, The City College of New York, New York, NY, USA
| | - Juan Pena
- Department of Biomedical Engineering, The City College of New York, New York, NY, USA
| | - Jing Zhou
- Department of Biology, Lehman College, Bronx, NY, USA.,Biology, The Graduate Center, The City University of New York, New York, NY, USA
| | - Stephen Redenti
- Department of Biology, Lehman College, Bronx, NY, USA.,Biology, The Graduate Center, The City University of New York, New York, NY, USA.,Biochemistry, The Graduate Center, The City University of New York, New York, NY, USA
| | - Robert Majeska
- Department of Biomedical Engineering, The City College of New York, New York, NY, USA
| | - Maribel Vazquez
- Department of Biomedical Engineering, The City College of New York, New York, NY, USA.,Biochemistry, The Graduate Center, The City University of New York, New York, NY, USA
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32
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Regenerative Medicine Applications of Mesenchymal Stem Cells. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2018; 1089:115-141. [PMID: 29767289 DOI: 10.1007/5584_2018_213] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
A major research challenge is to develop therapeutics that assist with healing damaged tissues and organs because the human body has limited ability to restore the majority of these tissues and organs to their original state. Tissue engineering (TE) and regenerative medicine (RM) promises to offer efficient therapeutic biological strategies that use mesenchymal stem cells (MSCs). MSCs possess the capability for self-renewal, multilineage differentiation, and immunomodulatory properties that make them attractive for clinical applications. They have been extensively investigated in numerous preclinical and clinical settings in an attempt to overcome their challenges and promote tissue regeneration and repair. This review explores the exciting opportunities afforded by MSCs, their desirable properties as cellular therapeutics in RM, and implicates their potential use in clinical practice. Here, we attempt to identify challenges and issues that determine the clinical efficacy of MSCs as treatment for skeletal and non-skeletal tissues.
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33
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Daliri K, Ljubimov AV, Hekmatimoghaddam S. Glaucoma, Stem Cells, and Gene Therapy: Where Are We Now? Int J Stem Cells 2017; 10:119-128. [PMID: 28844129 PMCID: PMC5741193 DOI: 10.15283/ijsc17029] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/20/2017] [Indexed: 12/17/2022] Open
Abstract
Glaucoma is the second most common cause of blindness, affecting 70∼80 million people around the world. The death of retinal ganglion cells (RGCs) is the main cause of blindness related to this disease. Current therapies do not provide enough protection and regeneration of RGCs. A novel opportunity for treatment of glaucoma is application of technologies related to stem cell and gene therapy. In this perspective we will thus focus on emerging approaches to glaucoma treatment including stem cells and gene therapy.
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Affiliation(s)
- Karim Daliri
- Neurogenetic Ward, Comprehensive Child Developmental Center, Shiraz University of Medical Sciences, Shiraz, Iran.,Visiting Scientist at Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, Germany
| | - Alexander V Ljubimov
- Regenerative Medicine Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.,Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Seyedhossein Hekmatimoghaddam
- Stem Cell Biology Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.,Department of Laboratory Sciences, School of Paramedicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
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34
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Differentiation of mesenchymal stem cells -derived trabecular meshwork into dopaminergic neuron-like cells on nanofibrous scaffolds. Biologicals 2017; 50:49-54. [DOI: 10.1016/j.biologicals.2017.09.002] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2017] [Revised: 09/06/2017] [Accepted: 09/11/2017] [Indexed: 11/23/2022] Open
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35
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Nasehi F, Karshenas M, Nadri S, Barati G, Salim A. Core-shell fibrous scaffold as a vehicle for sustained release of retinal pigmented epithelium-derived factor (PEDF) for photoreceptor differentiation of conjunctiva mesenchymal stem cells. J Biomed Mater Res A 2017; 105:3514-3519. [PMID: 28795779 DOI: 10.1002/jbm.a.36182] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2017] [Revised: 06/01/2017] [Accepted: 08/01/2017] [Indexed: 11/06/2022]
Abstract
Coaxial electrospinning technique was introduced as a flexible and promising technique for the fabrication of core-shell fibrous scaffold from poly ethylene glycol/poly caprolactone (PEG/PCL), where retinal pigmented epithelium-derived factor (PEDF) was encapsulated in the core, for photoreceptor differentiation of conjunctiva mesenchymal stem cells (CJMSCs) seed on scaffolds. The morphology and structure of fibers were characterized using SEM and TEM and photoreceptor differentiation was examined by quantitative real time PCR (qPCR). Release study showed that, a sustained release of PEDF from PEG/PCL scaffold was observed over 14 days. qPCR analysis demonstrated that rhodopsin (as a main photoreceptor gene) was significantly expressed in CJMSCs cultured on scaffold loaded with PEDF. According to the result, the core-shell scaffold loaded with PEDF (PEG + PEDF)/PCL) has superior control over factor release profile and has a potential for guiding photoreceptor differentiation of mesenchymal stem cells and promoting retinal regeneration. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3514-3519, 2017.
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Affiliation(s)
- Fatemeh Nasehi
- Department of Medical Biotechnology and Nanotechnology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Mohsen Karshenas
- Department of Mechanical Engineering, Amirkabir University of Technology (Tehran Polytechnic), Tehran, Iran
| | - Samad Nadri
- Department of Medical Biotechnology and Nanotechnology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.,Cancer Gene Therapy Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Ghasem Barati
- Department of Medical Biotechnology and Nanotechnology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Ahdiye Salim
- Department of Food Safety and Hygiene, School of Health, Zanjan University of Medical Sciences, Zanjan, Iran
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36
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Cellular Reparative Mechanisms of Mesenchymal Stem Cells for Retinal Diseases. Int J Mol Sci 2017; 18:ijms18081406. [PMID: 28788088 PMCID: PMC5577990 DOI: 10.3390/ijms18081406] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2017] [Revised: 06/09/2017] [Accepted: 06/12/2017] [Indexed: 12/22/2022] Open
Abstract
The use of multipotent mesenchymal stem cells (MSCs) has been reported as promising for the treatment of numerous degenerative disorders including the eye. In retinal degenerative diseases, MSCs exhibit the potential to regenerate into retinal neurons and retinal pigmented epithelial cells in both in vitro and in vivo studies. Delivery of MSCs was found to improve retinal morphology and function and delay retinal degeneration. In this review, we revisit the therapeutic role of MSCs in the diseased eye. Furthermore, we reveal the possible cellular mechanisms and identify the associated signaling pathways of MSCs in reversing the pathological conditions of various ocular disorders such as age-related macular degeneration (AMD), retinitis pigmentosa, diabetic retinopathy, and glaucoma. Current stem cell treatment can be dispensed as an independent cell treatment format or with the combination of other approaches. Hence, the improvement of the treatment strategy is largely subjected by our understanding of MSCs mechanism of action.
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37
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Yun H, Zhou Y, Wills A, Du Y. Stem Cells in the Trabecular Meshwork for Regulating Intraocular Pressure. J Ocul Pharmacol Ther 2016; 32:253-60. [PMID: 27183473 DOI: 10.1089/jop.2016.0005] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Intraocular pressure (IOP) is still the main treatment target for glaucoma. Outflow resistance mainly exists at the trabecular meshwork (TM) outflow pathway, which is responsible for IOP regulation. Changes of TM cellularity and TM extracellular matrix turnover may play important roles in IOP regulation. In this article, we review basic anatomy and physiology of the outflow pathway and TM stem cell characteristics regarding the location, isolation, identification and function. TM stem cells are localized at the insert region of the TM and are label-retaining in vivo. They can be isolated by side-population cell sorting, cloning culture, or sphere culture. TM stem cells are multipotent with the ability to home to the TM region and differentiate into TM cells in vivo. Other stem cell types, such as adipose-derived stem cells, mesenchymal stem cells and induced pluripotent stem cells have been discovered for TM cell differentiation and TM regeneration. We also review glaucomatous animal models, which are suitable to study stem cell-based therapies for TM regeneration.
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Affiliation(s)
- Hongmin Yun
- 1 Department of Ophthalmology, University of Pittsburgh , Pittsburgh, Pennsylvania
| | - Yi Zhou
- 1 Department of Ophthalmology, University of Pittsburgh , Pittsburgh, Pennsylvania.,2 Department of Ophthalmology, Xiangya Hospital, Central South University , Changsha, China
| | - Andrew Wills
- 1 Department of Ophthalmology, University of Pittsburgh , Pittsburgh, Pennsylvania.,3 Department of Chemistry, CUNY-City College of Technology , Brooklyn, New York
| | - Yiqin Du
- 1 Department of Ophthalmology, University of Pittsburgh , Pittsburgh, Pennsylvania.,4 Department of Developmental Biology, University of Pittsburgh , Pittsburgh, Pennsylvania.,5 Louis J. Fox Center for Vision Restoration, University of Pittsburgh , Pittsburgh, Pennsylvania.,6 McGowan Institute for Regenerative Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania
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38
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Pearson C, Martin K. Stem cell approaches to glaucoma: from aqueous outflow modulation to retinal neuroprotection. PROGRESS IN BRAIN RESEARCH 2015; 220:241-56. [PMID: 26497794 DOI: 10.1016/bs.pbr.2015.04.005] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Long-term pharmacological management of glaucoma currently relies on self-administered drugs to regulate intraocular pressure (IOP). A number of approaches using stem cells have recently shown promise as potential future treatment strategies complementary to IOP lowering. Several sources of endogenous stem cells have been identified in the eye, some of which may be able to repair the damaged trabecular meshwork and restore functional regulation of aqueous outflow. Neural and mesenchymal stem cells secrete growth factors which provide neuroprotective effects, reducing loss of retinal ganglion cells (RGCs) in animal models. In the future, stem cells may even replace RGCs to reform functional connections between the eye and the brain, although the complexity of such a repair task is formidable. With advances in biomaterial cell scaffolds and concurrent efforts in other neural systems, stem cell therapies are becoming a realistic option for treating multiple eye diseases, and despite ongoing challenges, there are reasons for optimism that stem cells may play a role in the treatment of human glaucoma in the future.
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Affiliation(s)
- Craig Pearson
- John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, UK; Cambridge NIHR Biomedical Research Centre, Cambridge, UK; National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - Keith Martin
- John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, UK; Cambridge NIHR Biomedical Research Centre, Cambridge, UK; Wellcome Trust Medical Research Council Cambridge Stem Cell Institute, Cambridge, UK.
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39
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Stem cell based therapies for age-related macular degeneration: The promises and the challenges. Prog Retin Eye Res 2015; 48:1-39. [PMID: 26113213 DOI: 10.1016/j.preteyeres.2015.06.004] [Citation(s) in RCA: 136] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2015] [Revised: 06/05/2015] [Accepted: 06/11/2015] [Indexed: 12/21/2022]
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40
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Roubeix C, Denoyer A, Brignole-Baudouin F, Baudouin C. [Mesenchymal stem cell therapy, a new hope for eye disease]. J Fr Ophtalmol 2015. [PMID: 26215486 DOI: 10.1016/j.jfo.2015.05.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Mesenchymal stem cells (MSC) are adult stem cells, first identified in skeletal tissues and then found in the entire body. MSC are able to not only differentiate into specialized cells within skeletal tissue - chondrocytes, osteocytes, adipocytes and fibroblasts - but also secrete a large range of soluble mediators defining their secretome and allowing their interaction with a number of cell protagonists. Thus, in a general sense, MSC are involved in tissue homeostasis through their secretome and are specifically responsible for cell turn-over in skeletal tissues. For a decade and a half, safety and efficiency of MSC has led to the development of many clinical trials in various fields. However, results were often disappointing, probably because of difficulties in methods and evaluation. At a time when the first clinical trials using MSC are emerging in ophthalmology, the goal of this literature review is to gather and put into perspective preclinical and clinical results in order to better predict the future of this innovative therapeutic pathway.
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Affiliation(s)
- C Roubeix
- Inserm, U968, 75012 Paris, France; UMR_S 968, institut de la vision, UPMC université Paris 06, 17, rue Moreau, 75012 Paris, France; CNRS, UMR_7210, 75012 Paris, France.
| | - A Denoyer
- Inserm, U968, 75012 Paris, France; UMR_S 968, institut de la vision, UPMC université Paris 06, 17, rue Moreau, 75012 Paris, France; CNRS, UMR_7210, 75012 Paris, France; Inserm-DHOS CIC 503, centre hospitalier national d'ophtalmologie des Quinze-Vingts, 75012 Paris, France
| | - F Brignole-Baudouin
- Inserm, U968, 75012 Paris, France; UMR_S 968, institut de la vision, UPMC université Paris 06, 17, rue Moreau, 75012 Paris, France; CNRS, UMR_7210, 75012 Paris, France; Inserm-DHOS CIC 503, centre hospitalier national d'ophtalmologie des Quinze-Vingts, 75012 Paris, France; Faculté de pharmacie de Paris, université Paris Descartes, Sorbonne Paris-Cité, 75006 Paris, France
| | - C Baudouin
- Inserm, U968, 75012 Paris, France; UMR_S 968, institut de la vision, UPMC université Paris 06, 17, rue Moreau, 75012 Paris, France; CNRS, UMR_7210, 75012 Paris, France; Inserm-DHOS CIC 503, centre hospitalier national d'ophtalmologie des Quinze-Vingts, 75012 Paris, France; Service d'ophtalmologie, hôpital Ambroise-Paré, AP-HP, 92100 Boulogne, France; Université Versailles-Saint-Quentin-en-Yvelines, 78180 Montigny-le-Bretonneux, France
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41
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Weiss JN, Levy S, Malkin A. Stem Cell Ophthalmology Treatment Study (SCOTS) for retinal and optic nerve diseases: a preliminary report. Neural Regen Res 2015. [PMID: 26199618 PMCID: PMC4498363 DOI: 10.4103/1673-5374.158365] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
In this report, we present the results of a single patient with optic neuropathy treated within the Stem Cell Ophthalmology Treatment Study (SCOTS). SCOTS is an Institutional Review Board approved clinical trial and is the largest ophthalmology stem cell study registered at the National Institutes of Health to date- www.clinicaltrials.gov Identifier NCT 01920867. SCOTS utilizes autologous bone marrow-derived stem cells in the treatment of optic nerve and retinal diseases. Pre- and post-treatment comprehensive eye exams were independently performed at the Wilmer Eye Institute at the Johns Hopkins Hospital, USA. A 27 year old female patient had lost vision approximately 5 years prior to enrollment in SCOTS. Pre-treatment best-corrected visual acuity at the Wilmer Eye Institute was 20/800 Right Eye (OD) and 20/4,000 Left Eye (OS). Four months following treatment in SCOTS, the central visual acuity had improved to 20/100 OD and 20/40 OS.
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Affiliation(s)
- Jeffrey N Weiss
- Retina Associates of South Florida, 5800 Colonial Drive, Suite 300, Margate, FL, USA
| | - Steven Levy
- MD Stem Cells, 412 Main Street, Suite I, Ridgefield, CT, USA
| | - Alexis Malkin
- Wilmer Eye Institute, The Johns Hopkins Hospital, 600 N. Wolfe Street, Wilmer 317, Baltimore, MD, USA
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Norouzi M, Boroujeni SM, Omidvarkordshouli N, Soleimani M. Advances in skin regeneration: application of electrospun scaffolds. Adv Healthc Mater 2015; 4:1114-33. [PMID: 25721694 DOI: 10.1002/adhm.201500001] [Citation(s) in RCA: 159] [Impact Index Per Article: 15.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2015] [Indexed: 12/28/2022]
Abstract
The paucity of cellular and molecular signals essential for normal wound healing makes severe dermatological ulcers stubborn to heal. The novel strategies of skin regenerative treatments are focused on the development of biologically responsive scaffolds accompanied by cells and multiple biomolecules resembling structural and biochemical cues of the natural extracellular matrix (ECM). Electrospun nanofibrous scaffolds provide similar architecture to the ECM leading to enhancement of cell adhesion, proliferation, migration and neo tissue formation. This Review surveys the application of biocompatible natural, synthetic and composite polymers to fabricate electrospun scaffolds as skin substitutes and wound dressings. Furthermore, the application of biomolecules and therapeutic agents in the nanofibrous scaffolds viz growth factors, genes, antibiotics, silver nanoparticles, and natural medicines with the aim of ameliorating cellular behavior, wound healing, and skin regeneration are discussed.
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Affiliation(s)
- Mohammad Norouzi
- Department of Nanotechnology and Tissue Engineering; Stem Cell Technology Research Center; Tehran Iran
| | | | | | - Masoud Soleimani
- Department of Hematology; Faculty of Medical Sciences; Tarbiat Modares University; Tehran Iran
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Nadri S, Yazdani S. Isolation and Expansion of Mesenchymal Stem Cells from Human Conjunctival Tissue. ACTA ACUST UNITED AC 2015; 33:1F.14.1-8. [DOI: 10.1002/9780470151808.sc01f14s33] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Affiliation(s)
- Samad Nadri
- Medical Biotechnology and Medical Nanotechnology Department, Faculty of Medicine, Zanjan University of Medical Science Zanjan Iran
| | - Shahin Yazdani
- Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences Tehran Iran
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Yu WY, Grierson I, Sheridan C, Lo ACY, Wong DSH. Bovine posterior limbus: an evaluation of an alternative source for corneal endothelial and trabecular meshwork stem/progenitor cells. Stem Cells Dev 2014; 24:624-39. [PMID: 25323922 DOI: 10.1089/scd.2014.0257] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
A growing body of evidence has revealed that stem-like cells in the posterior limbus of the eye between the corneal endothelium (CE) and trabecular meshwork (TM) may be able to rejuvenate these tissues in disease. However, these cells have not been clearly defined and we have named them PET cells (progenitor cells of the endothelium and trabeculum). A good and inexpensive animal model for PET cells is lacking, so we investigated bovine eyes as an effective large tissue source. We showed the presence of stem/progenitor cells in the bovine CE, transition zone, and TM in situ. Floating spheres cultured from the CE and TM showed similar stem cell marker expression patterns. Both the CE and TM spheres were bipotent and highly proliferative, but with limited secondary sphere-forming capability. They were highly prone to differentiate back into the cell type of their tissue of origin. It is speculated that the PET cells become more tissue-specific as they migrate away from their niche. Here, we showed that PET cells are present in the posterior limbus of bovine eyes and that they can be successfully cultured and expanded. PET cells represent an attractive target for developing new treatments to regenerate both the CE and TM, thereby reducing the requirement for donor tissue for corneal transplant and invasive treatments for glaucomatous patients.
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Affiliation(s)
- Wing Yan Yu
- 1 Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong , Hong Kong, China
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Recent advances of stem cell therapy for retinitis pigmentosa. Int J Mol Sci 2014; 15:14456-74. [PMID: 25141102 PMCID: PMC4159862 DOI: 10.3390/ijms150814456] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2014] [Revised: 07/24/2014] [Accepted: 08/11/2014] [Indexed: 12/22/2022] Open
Abstract
Retinitis pigmentosa (RP) is a group of inherited retinal disorders characterized by progressive loss of photoreceptors and eventually leads to retina degeneration and atrophy. Until now, the exact pathogenesis and etiology of this disease has not been clear, and many approaches for RP therapies have been carried out in animals and in clinical trials. In recent years, stem cell transplantation-based attempts made some progress, especially the transplantation of bone marrow-derived mesenchymal stem cells (BMSCs). This review will provide an overview of stem cell-based treatment of RP and its main problems, to provide evidence for the safety and feasibility for further clinical treatment.
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Ng TK, Fortino VR, Pelaez D, Cheung HS. Progress of mesenchymal stem cell therapy for neural and retinal diseases. World J Stem Cells 2014; 6:111-119. [PMID: 24772238 PMCID: PMC3999769 DOI: 10.4252/wjsc.v6.i2.111] [Citation(s) in RCA: 94] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Revised: 01/14/2014] [Accepted: 03/04/2014] [Indexed: 02/07/2023] Open
Abstract
Complex circuitry and limited regenerative power make central nervous system (CNS) disorders the most challenging and difficult for functional repair. With elusive disease mechanisms, traditional surgical and medical interventions merely slow down the progression of the neurodegenerative diseases. However, the number of neurons still diminishes in many patients. Recently, stem cell therapy has been proposed as a viable option. Mesenchymal stem cells (MSCs), a widely-studied human adult stem cell population, have been discovered for more than 20 years. MSCs have been found all over the body and can be conveniently obtained from different accessible tissues: bone marrow, blood, and adipose and dental tissue. MSCs have high proliferative and differentiation abilities, providing an inexhaustible source of neurons and glia for cell replacement therapy. Moreover, MSCs also show neuroprotective effects without any genetic modification or reprogramming. In addition, the extraordinary immunomodulatory properties of MSCs enable autologous and heterologous transplantation. These qualities heighten the clinical applicability of MSCs when dealing with the pathologies of CNS disorders. Here, we summarize the latest progress of MSC experimental research as well as human clinical trials for neural and retinal diseases. This review article will focus on multiple sclerosis, spinal cord injury, autism, glaucoma, retinitis pigmentosa and age-related macular degeneration.
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Suszynska M, Zuba-Surma EK, Maj M, Mierzejewska K, Ratajczak J, Kucia M, Ratajczak MZ. The proper criteria for identification and sorting of very small embryonic-like stem cells, and some nomenclature issues. Stem Cells Dev 2014; 23:702-713. [PMID: 24299281 PMCID: PMC3967357 DOI: 10.1089/scd.2013.0472] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2013] [Accepted: 11/27/2013] [Indexed: 01/14/2023] Open
Abstract
Evidence has accumulated that both murine and human adult tissues contain early-development stem cells with a broader differentiation potential than other adult monopotent stem cells. These cells, being pluripotent or multipotent, exist at different levels of specification and most likely represent overlapping populations of cells that, depending on the isolation strategy, ex vivo expansion protocol, and markers employed for their identification, have been given different names. In this review, we will discuss a population of very small embryonic-like stem cells (VSELs) in the context of other stem cells that express pluripotent/multipotent markers isolated from adult tissues as well as review the most current, validated working criteria on how to properly identify and isolate these very rare cells. VSELs have been successfully purified in several laboratories; however, a few have failed to isolate them, which has raised some unnecessary controversy in the field. Therefore, in this short review, we will address the most important reasons that some investigators have experienced problems in isolating these very rare cells and discuss some still unresolved challenges which should be overcome before these cells can be widely employed in the clinic.
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Affiliation(s)
- Malwina Suszynska
- Stem Cell Institute at the James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky
- Department of Physiology Pomeranian Medial University, Szczecin, Poland
| | - Ewa K. Zuba-Surma
- Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland
| | - Magdalena Maj
- Stem Cell Institute at the James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky
| | | | - Janina Ratajczak
- Stem Cell Institute at the James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky
- Department of Physiology Pomeranian Medial University, Szczecin, Poland
| | - Magda Kucia
- Stem Cell Institute at the James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky
- Department of Physiology Pomeranian Medial University, Szczecin, Poland
| | - Mariusz Z. Ratajczak
- Stem Cell Institute at the James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky
- Department of Physiology Pomeranian Medial University, Szczecin, Poland
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Current treatment limitations in age-related macular degeneration and future approaches based on cell therapy and tissue engineering. J Ophthalmol 2014; 2014:510285. [PMID: 24672707 PMCID: PMC3941782 DOI: 10.1155/2014/510285] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2013] [Accepted: 12/10/2013] [Indexed: 01/01/2023] Open
Abstract
Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world. With an ageing population, it is anticipated that the number of AMD cases will increase dramatically, making a solution to this debilitating disease an urgent requirement for the socioeconomic future of the European Union and worldwide. The present paper reviews the limitations of the current therapies as well as the socioeconomic impact of the AMD. There is currently no cure available for AMD, and even palliative treatments are rare. Treatment options show several side effects, are of high cost, and only treat the consequence, not the cause of the pathology. For that reason, many options involving cell therapy mainly based on retinal and iris pigment epithelium cells as well as stem cells are being tested. Moreover, tissue engineering strategies to design and manufacture scaffolds to mimic Bruch's membrane are very diverse and under investigation. Both alternative therapies are aimed to prevent and/or cure AMD and are reviewed herein.
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