Proteomic Profiling of the First Human Dental Pulp Mesenchymal Stem/Stromal Cells from Carbonic Anhydrase II Deficiency Osteopetrosis Patients

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2021 Jan 5

PMID 33396517

Citations 10

Authors

Zikra Alkhayal

Zakia Shinwari

Ameera Gaafar

Ayodele Alaiya

Affiliations

Soon will be listed here.

Abstract

Osteopetrosis is a hereditary disorder characterized by sclerotic, thick, weak, and brittle bone. The biological behavior of mesenchymal cells obtained from osteopetrosis patients has not been well-studied. Isolated mesenchymal stem/stromal cells from dental pulp (DP-MSSCs) of recently extracted deciduous teeth from osteopetrosis (OP) patients and healthy controls (HCs) were compared. We evaluated whether the dental pulp of OP patients has a population of MSSCs with similar multilineage differentiation capability to DP-MSSCs of healthy subjects. Stem/progenitor cells were characterized using immunohistochemistry, flow cytometry, and proteomics. Our DP-MSSCs were strongly positive for CD44, CD73, CD105, and CD90. DP-MSSCs obtained from HC subjects and OP patients showed similar patterns of proliferation and differentiation as well as gene expression. Proteomic analysis identified 1499 unique proteins with 94.3% similarity in global protein fingerprints of HCs and OP patients. Interestingly, we observed subtle differences in expressed proteins of osteopetrosis disease-related in pathways, including MAPK, ERK 1/2, PI3K, and integrin, rather than in the stem cell signaling network. Our findings of similar protein expression signatures in DP-MSSCs of HC and OP patients are of paramount interest, and further in vivo validation study is needed. There is the possibility that OP patients could have their exfoliating deciduous teeth banked for future use in regenerative dentistry.

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References

Gronthos S, Brahim J, Li W, Fisher L, Cherman N, Boyde A . Stem cell properties of human dental pulp stem cells. J Dent Res. 2002; 81(8):531-5. DOI: 10.1177/154405910208100806. View

Nagai R, Kooh S, Balfe J, Fenton T, Halperin M . Renal tubular acidosis and osteopetrosis with carbonic anhydrase II deficiency: pathogenesis of impaired acidification. Pediatr Nephrol. 1997; 11(5):633-6. DOI: 10.1007/s004670050354. View

Huang Y, Tang X, Cehreli Z, Dai X, Xu J, Zhu H . Autologous transplantation of deciduous tooth pulp into necrotic young permanent teeth for pulp regeneration in a dog model. J Int Med Res. 2019; 47(10):5094-5105. PMC: 6833418. DOI: 10.1177/0300060519862094. View

Del Fattore A, Peruzzi B, Rucci N, Recchia I, Cappariello A, Longo M . Clinical, genetic, and cellular analysis of 49 osteopetrotic patients: implications for diagnosis and treatment. J Med Genet. 2005; 43(4):315-25. PMC: 2563229. DOI: 10.1136/jmg.2005.036673. View

Love C, Sun Z, Jima D, Li G, Zhang J, Miles R . The genetic landscape of mutations in Burkitt lymphoma. Nat Genet. 2012; 44(12):1321-5. PMC: 3674561. DOI: 10.1038/ng.2468. View

Alaiya A, Aljurf M, Shinwari Z, Almohareb F, Malhan H, Alzahrani H . Protein signatures as potential surrogate biomarkers for stratification and prediction of treatment response in chronic myeloid leukemia patients. Int J Oncol. 2016; 49(3):913-33. PMC: 4948960. DOI: 10.3892/ijo.2016.3618. View

Miura M, Gronthos S, Zhao M, Lu B, Fisher L, Robey P . SHED: stem cells from human exfoliated deciduous teeth. Proc Natl Acad Sci U S A. 2003; 100(10):5807-12. PMC: 156282. DOI: 10.1073/pnas.0937635100. View

Penna S, Capo V, Palagano E, Sobacchi C, Villa A . One Disease, Many Genes: Implications for the Treatment of Osteopetroses. Front Endocrinol (Lausanne). 2019; 10:85. PMC: 6389615. DOI: 10.3389/fendo.2019.00085. View

Andrukhov O, Behm C, Blufstein A, Rausch-Fan X . Immunomodulatory properties of dental tissue-derived mesenchymal stem cells: Implication in disease and tissue regeneration. World J Stem Cells. 2019; 11(9):604-617. PMC: 6789188. DOI: 10.4252/wjsc.v11.i9.604. View

10.

Fu X, Jin L, Ma P, Fan Z, Wang S . Allogeneic stem cells from deciduous teeth in treatment for periodontitis in miniature swine. J Periodontol. 2013; 85(6):845-51. DOI: 10.1902/jop.2013.130254. View

11.

Yasui T, Mabuchi Y, Morikawa S, Onizawa K, Akazawa C, Nakagawa T . Isolation of dental pulp stem cells with high osteogenic potential. Inflamm Regen. 2017; 37:8. PMC: 5725894. DOI: 10.1186/s41232-017-0039-4. View

12.

Ohlsson A, Stark G, Sakati N . Marble brain disease: recessive osteopetrosis, renal tubular acidosis and cerebral calcification in three Saudi Arabian families. Dev Med Child Neurol. 1980; 22(1):72-84. DOI: 10.1111/j.1469-8749.1980.tb04307.x. View

13.

Kassem D, Kamal M, El-Kholy A, El-Mesallamy H . Exendin-4 enhances the differentiation of Wharton's jelly mesenchymal stem cells into insulin-producing cells through activation of various β-cell markers. Stem Cell Res Ther. 2016; 7(1):108. PMC: 4981957. DOI: 10.1186/s13287-016-0374-4. View

14.

Choi S, Kim S, Choi J, Park C, Shim W, Lim D . Fibroblast growth factor-2 and -4 promote the proliferation of bone marrow mesenchymal stem cells by the activation of the PI3K-Akt and ERK1/2 signaling pathways. Stem Cells Dev. 2008; 17(4):725-36. DOI: 10.1089/scd.2007.0230. View

15.

Urraca N, Memon R, El-Iyachi I, Goorha S, Valdez C, Tran Q . Characterization of neurons from immortalized dental pulp stem cells for the study of neurogenetic disorders. Stem Cell Res. 2015; 15(3):722-730. PMC: 4698085. DOI: 10.1016/j.scr.2015.11.004. View

16.

Ma L, Makino Y, Yamaza H, Akiyama K, Hoshino Y, Song G . Cryopreserved dental pulp tissues of exfoliated deciduous teeth is a feasible stem cell resource for regenerative medicine. PLoS One. 2012; 7(12):e51777. PMC: 3522596. DOI: 10.1371/journal.pone.0051777. View

17.

Zhang J, Yun M, Xu Y, Chen J, Weng H, Zheng Z . GNA13 as a prognostic factor and mediator of gastric cancer progression. Oncotarget. 2016; 7(4):4414-27. PMC: 4826215. DOI: 10.18632/oncotarget.6780. View

18.

Arany P, Cho A, Hunt T, Sidhu G, Shin K, Hahm E . Photoactivation of endogenous latent transforming growth factor-β1 directs dental stem cell differentiation for regeneration. Sci Transl Med. 2014; 6(238):238ra69. PMC: 4113395. DOI: 10.1126/scitranslmed.3008234. View

19.

Basmaeil Y, Algudiri D, Alenzi R, Subayyil A, Alaiya A, Khatlani T . HMOX1 is partly responsible for phenotypic and functional abnormalities in mesenchymal stem cells/stromal cells from placenta of preeclampsia (PE) patients. Stem Cell Res Ther. 2020; 11(1):30. PMC: 6975087. DOI: 10.1186/s13287-020-1557-6. View

20.

Kassem D, Kamal M, El-Kholy A, El-Mesallamy H . Association of expression levels of pluripotency/stem cell markers with the differentiation outcome of Wharton's jelly mesenchymal stem cells into insulin producing cells. Biochimie. 2016; 127:187-95. DOI: 10.1016/j.biochi.2016.05.019. View