Generation of Induced Pluripotent Stem Cells from Patients with Multiple Myeloma

Overview

Journal Turk J Haematol

Specialty Hematology

Date 2021 Mar 24

PMID 33757979

Citations 1

Authors

Irem Yilmaz Basaran

Erdal Karaoz

Affiliations

Soon will be listed here.

Abstract

Objective: Patient-specific induced pluripotent stem cells (iPSCs) have potential in human disease modeling and regenerative medicine. The in vitro phenotype of disease-specific iPSC-derived cells can be used to bridge the knowledge gap between clinical phenotype and molecular or cellular pathophysiology and to understand the pathology of diseases, along with further applications, such as creating new strategies for drug screening or developing novel therapeutic agents. The aim of our study was to generate iPSCs from multiple myeloma (MM) patients.

Materials And Methods: Mesenchymal stem cells (MSCs) isolated from MM patients were induced for pluripotency via the Sendai virus. Fibroblasts were used as a control. Microscopic analysis was performed daily. For colony selection, live staining was done using alkaline phosphatase staining. Reprogramming experiments were confirmed by flow cytometry, immunofluorescence (IF) staining, and gene expression analyses. To confirm the spontaneous differentiation potential, an in vitro embryonic body (EB) formation assay was performed.

Results: Fibroblasts and MSCs obtained from MM patients were reprogrammed using the Sendai virus, which contains reprogramming vectors with the four Yamanaka factors, Oct3/4, Sox2, Klf4, and c-Myc. Microscopic analysis revealed that the generated iPSCs possessed classical embryonic stem cell-like morphological characteristics. Reprogramming experiments further showed that both cell lines can be reprogrammed up to the pluripotent stage, which was confirmed by flow cytometry, IF staining, and gene expression analyses. Spontaneous differentiation potential was confirmed by in vitro EB formation assays.

Conclusion: iPSCs have been successfully obtained from MM patients for the first time. These cells could clarify the molecular mechanisms behind this disease.

Citing Articles

Exploring the promising potential of induced pluripotent stem cells in cancer research and therapy.

Chehelgerdi M, Dehkordi F, Chehelgerdi M, Kabiri H, Salehian-Dehkordi H, Abdolvand M Mol Cancer. 2023; 22(1):189.

PMID: 38017433 PMC: 10683363. DOI: 10.1186/s12943-023-01873-0.

References

Tian E, Zhan F, Walker R, Rasmussen E, Ma Y, Barlogie B . The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. N Engl J Med. 2003; 349(26):2483-94. DOI: 10.1056/NEJMoa030847. View

Edwards C, Zhuang J, Mundy G . The pathogenesis of the bone disease of multiple myeloma. Bone. 2008; 42(6):1007-13. PMC: 2474770. DOI: 10.1016/j.bone.2008.01.027. View

Todoerti K, Lisignoli G, Storti P, Agnelli L, Novara F, Manferdini C . Distinct transcriptional profiles characterize bone microenvironment mesenchymal cells rather than osteoblasts in relationship with multiple myeloma bone disease. Exp Hematol. 2009; 38(2):141-53. DOI: 10.1016/j.exphem.2009.11.009. View

Takahashi K, Yamanaka S . Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006; 126(4):663-76. DOI: 10.1016/j.cell.2006.07.024. View

Tan X, Dai Q, Guo T, Xu J, Dai Q . Efficient generation of transgene- and feeder-free induced pluripotent stem cells from human dental mesenchymal stem cells and their chemically defined differentiation into cardiomyocytes. Biochem Biophys Res Commun. 2017; 495(4):2490-2497. DOI: 10.1016/j.bbrc.2017.12.007. View

Jiang Z, Han Y, Cao X . Induced pluripotent stem cell (iPSCs) and their application in immunotherapy. Cell Mol Immunol. 2013; 11(1):17-24. PMC: 4002145. DOI: 10.1038/cmi.2013.62. View

Mundy G, Luben R, Raisz L, Oppenheim J, Buell D . Bone-resorbing activity in supernatants from lymphoid cell lines. N Engl J Med. 1974; 290(16):867-71. DOI: 10.1056/NEJM197404182901601. View

Brown M, Rondon E, Rajesh D, Mack A, Lewis R, Feng X . Derivation of induced pluripotent stem cells from human peripheral blood T lymphocytes. PLoS One. 2010; 5(6):e11373. PMC: 2894062. DOI: 10.1371/journal.pone.0011373. View

Doss M, Sachinidis A . Current Challenges of iPSC-Based Disease Modeling and Therapeutic Implications. Cells. 2019; 8(5). PMC: 6562607. DOI: 10.3390/cells8050403. View

10.

Papadimitriou K, Kostopoulos I, Tsopanidou A, Orologas-Stavrou N, Kastritis E, Tsitsilonis O . Ex Vivo Models Simulating the Bone Marrow Environment and Predicting Response to Therapy in Multiple Myeloma. Cancers (Basel). 2020; 12(8). PMC: 7463609. DOI: 10.3390/cancers12082006. View

11.

Terpos E, Ntanasis-Stathopoulos I, Christoulas D, Bagratuni T, Bakogeorgos M, Gavriatopoulou M . Semaphorin 4D correlates with increased bone resorption, hypercalcemia, and disease stage in newly diagnosed patients with multiple myeloma. Blood Cancer J. 2018; 8(5):42. PMC: 5945651. DOI: 10.1038/s41408-018-0075-6. View

12.

Karaoz E, Aksoy A, Ayhan S, Eker Sariboyaci A, Kaymaz F, Kasap M . Characterization of mesenchymal stem cells from rat bone marrow: ultrastructural properties, differentiation potential and immunophenotypic markers. Histochem Cell Biol. 2009; 132(5):533-46. DOI: 10.1007/s00418-009-0629-6. View

13.

Rabin N, Kyriakou C, Coulton L, Gallagher O, Buckle C, Benjamin R . A new xenograft model of myeloma bone disease demonstrating the efficacy of human mesenchymal stem cells expressing osteoprotegerin by lentiviral gene transfer. Leukemia. 2007; 21(10):2181-91. DOI: 10.1038/sj.leu.2404814. View

14.

Ebert A, Liang P, Wu J . Induced pluripotent stem cells as a disease modeling and drug screening platform. J Cardiovasc Pharmacol. 2012; 60(4):408-16. PMC: 3343213. DOI: 10.1097/FJC.0b013e318247f642. View

15.

Sochacki J, Devalle S, Reis M, de Moraes Maciel R, da Silveira Paulsen B, Brentani H . Generation of iPS cell lines from schizophrenia patients using a non-integrative method. Stem Cell Res. 2016; 17(1):97-101. DOI: 10.1016/j.scr.2016.05.017. View

16.

Jamshidi Adegani F, Langroudi L, Arefian E, Shafiee A, Dinarvand P, Soleimani M . A comparison of pluripotency and differentiation status of four mesenchymal adult stem cells. Mol Biol Rep. 2013; 40(5):3693-703. DOI: 10.1007/s11033-012-2445-7. View

17.

Stadtfeld M, Brennand K, Hochedlinger K . Reprogramming of pancreatic beta cells into induced pluripotent stem cells. Curr Biol. 2008; 18(12):890-4. PMC: 2819222. DOI: 10.1016/j.cub.2008.05.010. View

18.

Re S, Dogan A, Ben-Shachar D, Berger G, Werling A, Walitza S . Improved Generation of Induced Pluripotent Stem Cells From Hair Derived Keratinocytes - A Tool to Study Neurodevelopmental Disorders as ADHD. Front Cell Neurosci. 2018; 12:321. PMC: 6167495. DOI: 10.3389/fncel.2018.00321. View

19.

de Bruyne E, Bos T, Schuit F, Van Valckenborgh E, Menu E, Thorrez L . IGF-1 suppresses Bim expression in multiple myeloma via epigenetic and posttranslational mechanisms. Blood. 2010; 115(12):2430-40. DOI: 10.1182/blood-2009-07-232801. View

20.

Li X, Ling W, Pennisi A, Wang Y, Khan S, Heidaran M . Human placenta-derived adherent cells prevent bone loss, stimulate bone formation, and suppress growth of multiple myeloma in bone. Stem Cells. 2011; 29(2):263-73. PMC: 3175303. DOI: 10.1002/stem.572. View