PRDX6 Promotes the Differentiation of Human Mesenchymal Stem (Stromal) Cells to Insulin-Producing Cells

Gabr, Mahmoud M.; Zakaria, Mahmoud M.; Refaie, Ayman; Khater, Sherry M.; Ashamallah, Sylvia A.; Rashed, Sahar A.; Fouad, Ali M.; Ismail, Amani; Ghoneim, Mohamed A.

doi:10.1155/2020/7103053

Cited by 3 publications

(2 citation statements)

References 38 publications

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“…In a proteomic study, 3 proteins were differentially expressed from injured pancreata of Sprague-Dawley rats: cofilin1, nucleoside diphosphate kinase (NDPKA) and peroxiredoxin-6 (PRDX6) [ 100 ]. The yield of IPCs when these proteins were added to the differentiation medium alone or in combination was evaluated [ 101 ]. The best outcome was observed in samples supplemented with PRDX6 alone, where the yield of IPCs increased by 4-fold compared to that of the controls.…”

Section: From Mscs To Ipcsmentioning

confidence: 99%

From Mesenchymal Stromal/Stem Cells to Insulin-Producing Cells: Progress and Challenges

Ghoneim

Refaie

Elbassiouny

et al. 2020

Stem Cell Rev and Rep

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Mesenchymal stromal cells (MSCs) are an attractive option for cell therapy for type 1 diabetes mellitus (DM). These cells can be obtained from many sources, but bone marrow and adipose tissue are the most studied. MSCs have distinct advantages since they are nonteratogenic, nonimmunogenic and have immunomodulatory functions. Insulin-producing cells (IPCs) can be generated from MSCs by gene transfection, gene editing or directed differentiation. For directed differentiation, MSCs are usually cultured in a glucose-rich medium with various growth and activation factors. The resulting IPCs can control chemically-induced diabetes in immune-deficient mice. These findings are comparable to those obtained from pluripotent cells. PD-L1 and PD-L2 expression by MSCs is upregulated under inflammatory conditions. Immunomodulation occurs due to the interaction between these ligands and PD-1 receptors on T lymphocytes. If this function is maintained after differentiation, life-long immunosuppression or encapsulation could be avoided. In the clinical setting, two sites can be used for transplantation of IPCs: the subcutaneous tissue and the omentum. A 2-stage procedure is required for the former and a laparoscopic procedure for the latter. For either site, cells should be transplanted within a scaffold, preferably one from fibrin. Several questions remain unanswered. Will the transplanted cells be affected by the antibodies involved in the pathogenesis of type 1 DM? What is the functional longevity of these cells following their transplantation? These issues have to be addressed before clinical translation is attempted.

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Section: From Mscs To Ipcsmentioning

confidence: 99%

From Mesenchymal Stromal/Stem Cells to Insulin-Producing Cells: Progress and Challenges

Ghoneim

Refaie

Elbassiouny

et al. 2020

Stem Cell Rev and Rep

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“…At the end of the differentiation protocol, the percentage of cells testing positive for insulin and c-peptide was modest (~ 5%). The differentiation protocol was later optimized, and the yield increased by threefold to fourfold [ 11 ]. Published reports by several investigators support these findings [ 12 – 16 ].…”

Section: Introductionmentioning

confidence: 99%

Transplantation of insulin-producing cells derived from human mesenchymal stromal/stem cells into diabetic humanized mice

Ghoneim

Gabr²,

Refaie

et al. 2022

Stem Cell Res Ther

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Background The purpose of this study was to investigate allogenic immune responses following the transplantation of insulin-producing cells (IPCs) differentiated from human adipose tissue-derived stem cells (hAT-MSCs) into humanized mice. Methods hAT-MSCs were isolated from liposuction aspirates obtained from HLA-A2-negative healthy donors. These cells were expanded and differentiated into IPCs. HLA-A2-positive humanized mice (NOG-EXL) were divided into 4 groups: diabetic mice transplanted with IPCs, diabetic but nontransplanted mice, nondiabetic mice transplanted with IPCs and normal untreated mice. Three million differentiated cells were transplanted under the renal capsule. Animals were followed-up to determine their weight, glucose levels (2-h postprandial), and human and mouse insulin levels. The mice were euthanized 6–8 weeks posttransplant. The kidneys were explanted for immunohistochemical studies. Blood, spleen and bone marrow samples were obtained to determine the proportion of immune cell subsets (CD4+, CD8+, CD16+, CD19+ and CD69+), and the expression levels of HLA-ABC and HLA-DR. Results Following STZ induction, blood glucose levels increased sharply and were then normalized within 2 weeks after cell transplantation. In these animals, human insulin levels were measurable while mouse insulin levels were negligible throughout the observation period. Immunostaining of cell-bearing kidneys revealed sparse CD45+ cells. Immunolabeling and flow cytometry of blood, bone marrow and splenic samples obtained from the 3 groups of animals did not reveal a significant difference in the proportions of immune cell subsets or in the expression levels of HLA-ABC and HLA-DR. Conclusion Transplantation of IPCs derived from allogenic hAT-MSCs into humanized mice was followed by a muted allogenic immune response that did not interfere with the functionality of the engrafted cells. Our findings suggest that such allogenic cells could offer an opportunity for cell therapy for insulin-dependent diabetes without immunosuppression, encapsulation or gene manipulations. Graphical Abstract

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Human amniotic membrane scaffold enhances adipose mesenchymal stromal cell mitochondrial bioenergetics promoting their regenerative capacities

Abou-Shanab,

Gaser,

Soliman

et al. 2024

Mol Cell Biochem

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PRDX6 Promotes the Differentiation of Human Mesenchymal Stem (Stromal) Cells to Insulin-Producing Cells

Cited by 3 publications

References 38 publications

From Mesenchymal Stromal/Stem Cells to Insulin-Producing Cells: Progress and Challenges

From Mesenchymal Stromal/Stem Cells to Insulin-Producing Cells: Progress and Challenges

Transplantation of insulin-producing cells derived from human mesenchymal stromal/stem cells into diabetic humanized mice

Human amniotic membrane scaffold enhances adipose mesenchymal stromal cell mitochondrial bioenergetics promoting their regenerative capacities

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