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

Overview

Journal Biomed Res Int

Publisher Wiley

Specialties Biomedical Engineering
Biotechnology
General Medicine

Date 2020 Feb 14

PMID 32051828

Citations 3

Authors

Mahmoud M Gabr

Mahmoud M Zakaria

Ayman F Refaie

Sherry M Khater

Sylvia A Ashamallah

Sahar A Rashed

Ali M Fouad

Amani M Ismail

Mohamed A Ghoneim

Affiliations

Soon will be listed here.

Abstract

Mesenchymal stem cells (MSCs) can be differentiated in vitro to form insulin-producing cells (IPCs). However, the proportion of induced cells is modest. Extracts from injured pancreata of rodents promoted this differentiation, and three upregulated proteins were identified in these extracts. The aim of this study was to evaluate the potential benefits of adding these proteins to the differentiation medium alone or in combination. Our results indicate that the proportion of IPCs among the protein(s)-supplemented samples was significantly higher than that in the samples with no added proteins. The yield from samples supplemented with PRDX6 alone was 4-fold higher than that from samples without added protein. These findings were also supported by the results of fluorophotometry. Gene expression profiles revealed higher levels among protein-supplemented samples. Significantly higher levels of GGT, SST, Glut-2, and MafB expression were noted among PRDX6-treated samples. There was a stepwise increase in the release of insulin and c-peptide, as a function of increasing glucose concentrations, indicating that the differentiated cells were glucose sensitive and insulin responsive. PRDX6 exerts its beneficial effects as a result of its biological antioxidant properties. Considering its ease of use as a single protein, PRDX6 is now routinely used in our differentiation protocols.

Citing Articles

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

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

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References

Sulzbacher S, Schroeder I, Truong T, Wobus A . Activin A-induced differentiation of embryonic stem cells into endoderm and pancreatic progenitors-the influence of differentiation factors and culture conditions. Stem Cell Rev Rep. 2009; 5(2):159-73. DOI: 10.1007/s12015-009-9061-5. View

Eudy J, Yao S, Weston M, Ma-Edmonds M, Talmadge C, Cheng J . Isolation of a gene encoding a novel member of the nuclear receptor superfamily from the critical region of Usher syndrome type IIa at 1q41. Genomics. 1998; 50(3):382-4. DOI: 10.1006/geno.1998.5345. View

Kim Y, Lee J, Shin J, Kim H, Kim C . Enhancement of mouse pancreatic regeneration and HIT-T15 cell proliferation with rat pancreatic extract. Biochem Biophys Res Commun. 2003; 309(3):528-32. DOI: 10.1016/j.bbrc.2003.07.011. View

Sun Y, Chen L, Hou X, Hou W, Dong J, Sun L . Differentiation of bone marrow-derived mesenchymal stem cells from diabetic patients into insulin-producing cells in vitro. Chin Med J (Engl). 2007; 120(9):771-6. View

Choi K, Shin J, Lee J, Kim Y, Kim S, Kim C . In vitro trans-differentiation of rat mesenchymal cells into insulin-producing cells by rat pancreatic extract. Biochem Biophys Res Commun. 2005; 330(4):1299-305. DOI: 10.1016/j.bbrc.2005.03.111. View

Sharapov M, Ravin V, Novoselov V . [Peroxyredoxins as multifunctional enzymes]. Mol Biol (Mosk). 2015; 48(4):600-28. View

Gabr M, Zakaria M, Refaie A, Ismail A, Abou-El-Mahasen M, Ashamallah S . Insulin-producing cells from adult human bone marrow mesenchymal stem cells control streptozotocin-induced diabetes in nude mice. Cell Transplant. 2012; 22(1):133-45. PMC: 3893040. DOI: 10.3727/096368912X647162. View

Oh S, Muzzonigro T, Bae S, Laplante J, Hatch H, Petersen B . Adult bone marrow-derived cells trans-differentiating into insulin-producing cells for the treatment of type I diabetes. Lab Invest. 2004; 84(5):607-17. DOI: 10.1038/labinvest.3700074. View

Zhang B, Yin Y, Lai R, Tan S, Choo A, Lim S . Mesenchymal stem cells secrete immunologically active exosomes. Stem Cells Dev. 2013; 23(11):1233-44. DOI: 10.1089/scd.2013.0479. View

10.

Hardikar A, Bhonde R . Modulating experimental diabetes by treatment with cytosolic extract from the regenerating pancreas. Diabetes Res Clin Pract. 2000; 46(3):203-11. DOI: 10.1016/s0168-8227(99)00098-4. View

11.

Prabakar K, Dominguez-Bendala J, Molano R, Pileggi A, Villate S, Ricordi C . Generation of glucose-responsive, insulin-producing cells from human umbilical cord blood-derived mesenchymal stem cells. Cell Transplant. 2011; 21(6):1321-39. DOI: 10.3727/096368911X612530. View

12.

Fu X, Chen Y, Xie F, Dong P, Liu W, Cao Y . Comparison of immunological characteristics of mesenchymal stem cells derived from human embryonic stem cells and bone marrow. Tissue Eng Part A. 2014; 21(3-4):616-26. PMC: 4334098. DOI: 10.1089/ten.TEA.2013.0651. View

13.

Yabe S, Fukuda S, Takeda F, Nashiro K, Shimoda M, Okochi H . Efficient generation of functional pancreatic β-cells from human induced pluripotent stem cells. J Diabetes. 2016; 9(2):168-179. DOI: 10.1111/1753-0407.12400. View

14.

Hosseinikia R, Nikbakht M, Moghaddam A, Tajehmiri A, Hosseinikia M, Oubari F . Molecular and Cellular Interactions of Allogenic and Autologus Mesenchymal Stem Cells with Innate and Acquired Immunity and Their Role in Regenerative Medicine. Int J Hematol Oncol Stem Cell Res. 2017; 11(1):63-77. PMC: 5338285. View

15.

Gabr M, Zakaria M, Refaie A, Abdel-Rahman E, Reda A, Ali S . From Human Mesenchymal Stem Cells to Insulin-Producing Cells: Comparison between Bone Marrow- and Adipose Tissue-Derived Cells. Biomed Res Int. 2017; 2017:3854232. PMC: 5444016. DOI: 10.1155/2017/3854232. View

16.

Abumaree M, Al Jumah M, Pace R, Kalionis B . Immunosuppressive properties of mesenchymal stem cells. Stem Cell Rev Rep. 2011; 8(2):375-92. DOI: 10.1007/s12015-011-9312-0. View

17.

Thatava T, Tayaramma T, Ma B, Rohde M, Mayer H . Chromatin-remodeling factors allow differentiation of bone marrow cells into insulin-producing cells. Stem Cells. 2006; 24(12):2858-67. DOI: 10.1634/stemcells.2006-0109. View

18.

Xin Y, Jiang X, Wang Y, Su X, Sun M, Zhang L . Insulin-Producing Cells Differentiated from Human Bone Marrow Mesenchymal Stem Cells In Vitro Ameliorate Streptozotocin-Induced Diabetic Hyperglycemia. PLoS One. 2016; 11(1):e0145838. PMC: 4710504. DOI: 10.1371/journal.pone.0145838. View

19.

Strem B, Hicok K, Zhu M, Wulur I, Alfonso Z, Schreiber R . Multipotential differentiation of adipose tissue-derived stem cells. Keio J Med. 2005; 54(3):132-41. DOI: 10.2302/kjm.54.132. View

20.

Forsyth N, Evans A, Shay J, Wright W . Developmental differences in the immortalization of lung fibroblasts by telomerase. Aging Cell. 2003; 2(5):235-43. DOI: 10.1046/j.1474-9728.2003.00057.x. View