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Fulltext Empowering Mesenchymal Stem Cells for Ocular Degenerative Disorders

Ding SSL, Subbiah SK, Khan MSA, Farhana A, Mok PL

Int J Mol Sci, 2019 Apr 10;20(7).
PMID: 30974904 DOI: 10.3390/ijms20071784

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.

Matched MeSH terms: Mesenchymal Stromal Cells/pathology
Small interfering RNA silencing of interleukin-6 in mesenchymal stromal cells inhibits multiple myeloma cell growth

Teoh HK, Chong PP, Abdullah M, Sekawi Z, Tan GC, Leong CF, et al.

Leuk. Res., 2016 Jan;40:44-53.
PMID: 26626206 DOI: 10.1016/j.leukres.2015.10.004

Studies demonstrated that mesenchymal stromal cells (MSC) from bone marrow stroma produced high concentration of interleukin-6 (IL-6) that promoted multiple myeloma cell growth. In view of the failure of IL-6 monoclonal antibody therapy to demonstrate substantial clinical responses in early clinical trials, more effective methods are needed in order to disrupt the favourable microenvironment provided by the bone marrow stroma. In this study, we evaluated the short interfering RNA (siRNA)-mediated silencing of IL-6 in MSC and the efficacy of these genetically modified MSC, with IL-6 suppression, on inhibition of U266 multiple myeloma cell growth. IL-6 mRNA and protein were significantly suppressed by 72h post IL-6 siRNA transfection without affecting the biological properties of MSC. Here we show significant inhibition of cell growth and IL-6 production in U266 cells co-cultured with MSC transfected with IL-6 siRNA when compared to U266 cells co-cultured with control MSC. We also show that the tumour volume and mitotic index of tumours in nude mice co-injected with U266 and MSC transfected with IL-6 siRNA were significantly reduced compared to tumours of mice co-injected with control MSC. Our results suggest potential use of RNA interference mediated therapy for multiple myeloma.

Matched MeSH terms: Mesenchymal Stromal Cells/pathology*
Assessment of tumourigenic potential in long-term cryopreserved human adipose-derived stem cells

Yong KW, Safwani WKZW, Xu F, Zhang X, Choi JR, Abas WABW, et al.

J Tissue Eng Regen Med, 2017 08;11(8):2217-2226.
PMID: 26756982 DOI: 10.1002/term.2120

Cryopreservation represents an efficient way to preserve human mesenchymal stem cells (hMSCs) at early culture/passage, and allows pooling of cells to achieve sufficient cells required for off-the-shelf use in clinical applications, e.g. cell-based therapies and regenerative medicine. To fully apply cryopreserved hMSCs in a clinical setting, it is necessary to evaluate their biosafety, e.g. chromosomal abnormality and tumourigenic potential. To date, many studies have demonstrated that cryopreserved hMSCs display no chromosomal abnormalities. However, the tumourigenic potential of cryopreserved hMSCs has not yet been evaluated. In the present study, we cryopreserved human adipose-derived mesenchymal stem cells (hASCs) for 3 months, using a slow freezing method with various cryoprotective agents (CPAs), followed by assessment of the tumourigenic potential of the cryopreserved hASCs after thawing and subculture. We found that long-term cryopreserved hASCs maintained normal levels of the tumour suppressor markers p53, p21, p16 and pRb, hTERT, telomerase activity and telomere length. Further, we did not observe significant DNA damage or signs of p53 mutation in cryopreserved hASCs. Our findings suggest that long-term cryopreserved hASCs are at low risk of tumourigenesis. These findings aid in establishing the biosafety profile of cryopreserved hASCs, and thus establishing low hazardous risk perception with the use of long-term cryopreserved hASCs for future clinical applications. Copyright © 2016 John Wiley & Sons, Ltd.

Matched MeSH terms: Mesenchymal Stromal Cells/pathology
Adipose-Derived Mesenchymal Stem Cells Promote Growth and Migration of Lung Adenocarcinoma Cancer Cells

Zakaria N, Yahaya BH

Adv Exp Med Biol, 2020;1292:83-95.
PMID: 31916234 DOI: 10.1007/5584_2019_464

INTRODUCTION: Mesenchymal stem cells (MSCs) have been used in cancer therapy as vehicles to deliver therapeutic materials such as drugs, apoptosis inducers and cytokines due to their ability to migrate and home at the tumour site. Furthermore, MSCs have been genetically engineered to produce anticancer molecules such as TRAIL that can induce apoptosis of cancer cells. However, MSCs' presence in the tumour microenvironment has shown to be involved in promoting tumour growth and progression. Therefore, the roles of MSCs either promoting or suppressing tumorigenesis need to be investigated.
METHODS: Human adipose-derived MSCs (Ad-MSCs) and A549 cells are co-cultured together in indirect co-culture system using Transwell insert. Following co-culture, both cells were analysed in terms of growth rate, migration ability, apoptosis and gene expression for genes involved in migration and stemness characteristics.
RESULTS: The result shows that Ad-MSCs promoted the growth of A549 cells when indirectly co-cultured for 48 and 72 h. Furthermore, Ad-MSCs significantly enhanced the migration rate of A549 cells. The increased in migration rate was in parallel with the significant increase of MMP9. There are no significant changes observed in the expression of TWIST2, CDH2 and CDH1, genes involved in the epithelial-to-mesenchymal transition (EMT). Ad-MSCs also protect A549 cancer cells from undergoing apoptosis and increase the survival of cancer cells.
CONCLUSION: Secretion of soluble factors from Ad-MSCs has been shown to promote the growth and metastatic characteristics of A549 cancer cells. Therefore, the use of Ad-MSCs in cancer therapy needs to be carefully evaluated in the long-term aspect.

Matched MeSH terms: Mesenchymal Stromal Cells/pathology*
Mesenchymal stem cells: From stem cells to sarcomas

Lye KL, Nordin N, Vidyadaran S, Thilakavathy K

Cell Biol Int, 2016 Jun;40(6):610-8.
PMID: 26992453 DOI: 10.1002/cbin.10603

Mesenchymal stem cells (MSCs) have garnered vast interests in clinical settings, especially in regenerative medicine due to their unique properties-they are reliably isolated and expanded from various tissue sources; they are able to differentiate into mesodermal tissues such as bones, cartilages, adipose tissues, and muscles; and they have unique immunosuppressive properties. However, there are some concerns pertaining to the role of MSCs in the human body. On one hand, they are crucial component in the regeneration and repair of the human body. On the contrary, they are shown to transform into sarcomas. Although the exact mechanisms are still unknown, many new leads have pointed to the belief that MSCs do play a role in sarcomagenesis. This review focuses on the current updates and findings of the role of MSCs in their transformation process into sarcomas.

Matched MeSH terms: Mesenchymal Stromal Cells/pathology*
In Vitro Methods to Evaluate the Effects of Mesenchymal Stem Cells on TGF-β1-Induced Pulmonary Fibrosis

Lan YW, Chen CM, Chong KY

Methods Mol Biol, 2021;2269:83-92.
PMID: 33687673 DOI: 10.1007/978-1-0716-1225-5_6

A co-culture model of mesenchymal stem cells (MSCs) and fibroblasts is an efficient and rapid method to evaluate the anti-fibrotic effects of MSCs-based cell therapy. Transforming growth factor (TGF)-β1 plays a key role in promotion of fibroblast activation and differentiation which can induce collagen deposition, increase ECM production in lung tissue, eventually resulted in pulmonary fibrosis. Here, we use this co-culture system and examine the ECM production in activated fibroblasts by western blot and quantitative real-time analysis to understand the therapeutic effects of MSCs.

Matched MeSH terms: Mesenchymal Stromal Cells/pathology
Differentiation of human mesenchymal stem cells into mesangial cells in post-glomerular injury murine model

Wong CY, Cheong SK, Mok PL, Leong CF

Pathology, 2008 Jan;40(1):52-7.
PMID: 18038316

AIMS: Adult human bone marrow contains a population of mesenchymal stem cells (MSC) that contributes to the regeneration of tissues such as bone, cartilage, muscle, tendon, and fat. In recent years, it has been shown that functional stem cells exist in the adult bone marrow, and they can contribute to renal remodelling or reconstitution of injured renal glomeruli, especially mesangial cells. The purpose of this study is to examine the ability of MSC isolated from human bone marrow to differentiate into mesangial cells in glomerular injured athymic mice.
METHODS: MSC were isolated from human bone marrow mononuclear cells based on plastic adherent properties and expanded in vitro in the culture medium. Human mesenchymal stem cells (hMSC) were characterised using microscopy, immunophenotyping, and their ability to differentiate into adipocytes, chondrocytes, and osteocytes. hMSC were then injected into athymic mice, which had induced glomerulonephropathy (GN).
RESULTS: Test mice (induced GN and infused hMSC) were shown to have anti-human CD105(+) cells present in the kidneys and were also positive to anti-human desmin, a marker for mesangial cells. Furthermore, immunofluorescence assays also demonstrated that anti-human desmin(+) cells in the glomeruli of these test mice were in the proliferation stage, being positive to anti-human Ki-67.
CONCLUSIONS: These findings indicate that hMSC found in renal glomeruli differentiated into mesangial cells in vivo after glomerular injury occurred.

Matched MeSH terms: Mesenchymal Stromal Cells/pathology*
Fulltext Proliferative activity of cells from remaining dental pulp in response to treatment with dental materials

Lutfi AN, Kannan TP, Fazliah MN, Jamaruddin MA, Saidi J

Aust Dent J, 2010 Mar;55(1):79-85.
PMID: 20415916 DOI: 10.1111/j.1834-7819.2009.01185.x

The biological examination of pulp injury, repair events and response of dental pulp stem cells to dental restorative materials is important to accomplish restorative treatment, especially to commonly used dental materials in paediatric dentistry, such as glass ionomer cement (GIC) and calcium hydroxide (Ca(OH)(2)) lining cement.

Matched MeSH terms: Mesenchymal Stromal Cells/pathology