Log in

Differential Expression of the hTERT Gene in Umbilical Cord-Derived Mesenchymal Stem Cells Cocultured with B Cell Precursor Leukemia Cell Microparticles or CD41+/CD61+ Platelet Microparticles

  • Original Article
  • Published:
Biochemical Genetics Aims and scope Submit manuscript

Abstract

Several investigations are being done to increase the short lifetime of mesenchymal stem cells (MSCs). One of the crucial genes involved in the immortalization of MSCs, hTERT (human telomerase reverse transcriptase), is activated in most publications using viral-based techniques. In this work, we investigated the use of platelet-derived (PMPs) and B cell precursor leukemia-derived microparticles as a nonviral method to trigger and compare the expression of the hTERT gene in MSCs. MSCs were extracted from the umbilical cord for the current investigation and identified using a flow cytometry approach and an inverted microscope. The Nalm-6 cell line and platelet concentrate were used to isolate microparticles (MPs). MSCs and MPs were cocultured for 14 days at 25-, 50-, and 100 μg/ml concentrations. qRT-PCR was used to research the expression of the hTERT gene. SPSS 26.0’s t test was used to compare the outcomes. After coculture with platelet MPs, MSCs had higher levels of hTERT gene expression than the control group. In contrast, this gene’s expression was concurrently decreased in MSCs exposed to MPs generated from Nalm-6. We demonstrated that following 14-day treatment, PMP significantly boosted the hTERT gene expression in MSCs, while the Nalm-6 MPs lowered the gene expression. However, additional studies are necessary due to the stability of hTERT gene expression and the immortalization of MSCs following exposure.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Data Availability

The data would be available from the corresponding author upon reasonable request.

References

  • Acebes-Huerta A et al (2020) Platelet-derived bio-products: classification update, applications, concerns and new perspectives. Transfus Apheres Sci 59(1):102716

    Article  Google Scholar 

  • Al-Azab M et al (2022) Aging of mesenchymal stem cell: machinery, markers, and strategies of fighting. Cell Mol Biol Lett 27(1):1–40

    Article  Google Scholar 

  • Apolonia L (2020) The old and the new: prospects for non-integrating lentiviral vector technology. Viruses 12(10):1103

    Article  CAS  PubMed Central  Google Scholar 

  • Ayala-Cuellar AP et al (2019) Characterization of canine adipose tissue-derived mesenchymal stem cells immortalized by SV40-T retrovirus for therapeutic use. J Cell Physiol 234(9):16630–16642

    Article  CAS  PubMed  Google Scholar 

  • Balaphas A et al (2019) Platelets and platelet-derived extracellular vesicles in liver physiology and disease. Hepatol Commun 3(7):855–866

    Article  PubMed  PubMed Central  Google Scholar 

  • Cecerska-Heryć E et al (2022) Applications of the regenerative capacity of platelets in modern medicine. Cytokine Growth Factor Rev 64:84–94

    Article  PubMed  Google Scholar 

  • Chen F et al (2019) Role of platelet microparticles in blood diseases: future clinical perspectives. Ann Clin Lab Sci 49(2):161–170

    CAS  PubMed  Google Scholar 

  • Choi HY et al (2015) Mesenchymal stem cell-derived microparticles ameliorate peritubular capillary rarefaction via inhibition of endothelial-mesenchymal transition and decrease tubulointerstitial fibrosis in unilateral ureteral obstruction. Stem Cell Res Ther 6:1–12

    Article  CAS  Google Scholar 

  • Clewell RA, Andersen ME (2016) Approaches for characterizing threshold dose–response relationships for DNA-damage pathways involved in carcinogenicity in vivo and micronuclei formation in vitro. Mutagenesis 31(3):333–340

    Article  CAS  PubMed  Google Scholar 

  • Crippa S et al (2019) Bone marrow-derived mesenchymal stromal cells: a novel target to optimize hematopoietic stem cell transplantation protocols in hematological malignancies and rare genetic disorders. J Clin Med 9(1):2

    Article  PubMed  PubMed Central  Google Scholar 

  • Eggenhofer E et al (2014) The life and fate of mesenchymal stem cells. Front Immunol 5:148

    Article  PubMed  PubMed Central  Google Scholar 

  • Fathi E et al (2019) Telomere shortening as a hallmark of stem cell senescence. Stem Cell Invest. https://doi.org/10.21037/sci.2019.02.04

    Article  Google Scholar 

  • Guerard M et al (2015) Assessment of mechanisms driving non-linear dose–response relationships in genotoxicity testing. Mutat Res Rev Mutat Res 763:181–201

    Article  CAS  PubMed  Google Scholar 

  • Guiotto M et al (2020) Human platelet lysate to substitute fetal bovine serum in hMSC expansion for translational applications: a systematic review. J Transl Med 18(1):1–14

    Article  Google Scholar 

  • Haghighitalab A et al (2021) Investigating the effects of IDO1, PTGS2, and TGF-β1 overexpression on immunomodulatory properties of hTERT-MSCs and their extracellular vesicles. Sci Rep 11(1):7825

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hannen R, Bartsch JW (2018) Essential roles of telomerase reverse transcriptase hTERT in cancer stemness and metastasis. FEBS Lett 592(12):2023–2031

    Article  CAS  PubMed  Google Scholar 

  • Harris E, Elmer JJ (2021) Optimization of electroporation and other nonviral gene delivery strategies for T cells. Biotechnol Prog 37(1):e3066

    Article  CAS  PubMed  Google Scholar 

  • Jiang W, Xu J (2020) Immune modulation by mesenchymal stem cells. Cell Prolif 53(1):e12712

    Article  PubMed  Google Scholar 

  • Kim JH et al (2021) Improved bladder contractility after transplantation of human mesenchymal stem cells overexpressing hepatocyte growth factor into underactive bladder from bladder outlet obstruction models of rats. PLoS ONE 16(12):e0261402

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lagarde F et al (2015) Non-monotonic dose-response relationships and endocrine disruptors: a qualitative method of assessment. Environ Health 14:1–15

    Article  Google Scholar 

  • Leão R et al (2018) Mechanisms of human telomerase reverse transcriptase (hTERT) regulation: clinical impacts in cancer. J Biomed Sci 25(1):1–12

    Article  Google Scholar 

  • Li C, Samulski RJ (2020) Engineering adeno-associated virus vectors for gene therapy. Nat Rev Genet 21(4):255–272

    Article  CAS  PubMed  Google Scholar 

  • Li Y et al (2017) Senescence of mesenchymal stem cells. Int J Mol Med 39(4):775–782

    Article  CAS  PubMed  Google Scholar 

  • Li Y et al (2022) Current status of clinical trials assessing mesenchymal stem cell therapy for graft versus host disease: a systematic review. Stem Cell Res Ther 13(1):1–22

    Google Scholar 

  • Li S et al (2023) Tanshinone IIA enhances the therapeutic efficacy of mesenchymal stem cells derived exosomes in myocardial ischemia/reperfusion injury via up-regulating miR-223-5p. J Control Release 358:13–26

    Article  CAS  PubMed  Google Scholar 

  • Lv F-J et al (2014) Concise review: the surface markers and identity of human mesenchymal stem cells. Stem Cells 32(6):1408–1419

    Article  CAS  PubMed  Google Scholar 

  • Mabrouk M et al (2022) The pathophysiological role of platelet-derived extracellular vesicles. Semin Thromb Hemostasis. https://doi.org/10.1055/s-0042-1756705

    Article  Google Scholar 

  • Maouia A et al (2020) The immune nature of platelets revisited. Transfus Med Rev 34(4):209–220

    Article  PubMed  PubMed Central  Google Scholar 

  • Maurer AC, Weitzman MD (2020) Adeno-associated virus genome interactions important for vector production and transduction. Hum Gene Ther 31(9–10):499–511

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mazini L et al (2019) Regenerative capacity of adipose derived stem cells (ADSCs), comparison with mesenchymal stem cells (MSCs). Int J Mol Sci 20(10):2523

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mazini L et al (2020) Hopes and limits of adipose-derived stem cells (ADSCs) and mesenchymal stem cells (MSCs) in wound healing. Int J Mol Sci 21(4):1306

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nazari M et al (2021) Platelet microparticle controversial role in cancer. Adv Pharm Bull 11(1):39

    Article  CAS  PubMed  Google Scholar 

  • Neto MD, Oliveira MB, Mano JF (2019) Microparticles in contact with cells: from carriers to multifunctional tissue modulators. Trends Biotechnol 37(9):1011–1028

    Article  CAS  PubMed  Google Scholar 

  • Petrich J et al (2020) Gene replacement therapy: a primer for the health-system pharmacist. J Pharm Pract 33(6):846–855

    Article  PubMed  Google Scholar 

  • Pour MSS et al (2017) Platelet-derived microparticles increase expression of hTERT in umbilical cord mesenchymal stem cells. Res Mol Med (RMM) 5:31–40

    Article  CAS  Google Scholar 

  • Pour MSS et al (2021) Platelet microparticles accelerate proliferation and growth of mesenchymal stem cells through longevity-related genes. Arch Iran Med 24(8):607–614

    Article  Google Scholar 

  • Provost P (2017) The clinical significance of platelet microparticle-associated microRNAs. Clin Chem Lab Med (CCLM) 55(5):657–666

    Article  CAS  PubMed  Google Scholar 

  • Sarvar DP et al (2022) Mesenchymal stromal cell-derived extracellular vesicles: novel approach in hematopoietic stem cell transplantation. Stem Cell Res Ther 13(1):202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tan KL et al (2021) Benchtop isolation and characterisation of small extracellular vesicles from human mesenchymal stem cells. Mol Biotechnol 63(9):780–791

    Article  CAS  PubMed  Google Scholar 

  • Weiss ARR, Dahlke MH (2019) Immunomodulation by mesenchymal stem cells (MSCs): mechanisms of action of living, apoptotic, and dead MSCs. Front Immunol 10:1191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yasumura Y et al (2023) Immortalized canine adipose-derived mesenchymal stem cells as a novel candidate cell source for mesenchymal stem cell therapy. Int J Mol Sci 24(3):2250

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao L et al (2019) The role of mesenchymal stem cells in hematopoietic stem cell transplantation: prevention and treatment of graft-versus-host disease. Stem Cell Res Ther 10(1):1–13

    Article  Google Scholar 

  • Zheng X et al (2021) The elevated level of IL-1α in the bone marrow of aged mice leads to MSC senescence partly by down-regulating Bmi-1. Exp Gerontol 148:111313

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, and Iranian Blood Transfusion Organization, Tehran, funded this research.

Funding

The Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, and Iranian Blood Transfusion Organization, Tehran, Iran.

Author information

Authors and Affiliations

Authors

Contributions

FY: investigation, writing—original draft, visualization, methodology. MHA: formal analysis, writing- reviewing and editing. NA: methodology, writing—reviewing and editing. MN: methodology, writing- reviewing and editing. HMV: formal analysis, writing- reviewing and editing. RMK: conceptualization, supervision, methodology, formal analysis, validation, writing- reviewing and editing.

Corresponding author

Correspondence to Roohollah Mirzaee Khalilabadi.

Ethics declarations

Competing Interests

The authors declare that they have no competing interests.

Ethics Approval and Consent to Participate

The study gained the approval of the ethical committee of The Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, and Iranian Blood Transfusion Organization, Tehran, Iran. All methods were performed following the relevant guidelines and regulations.

Consent for Publication

Not applicable.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yari, F., Ashoub, M.H., Amirizadeh, N. et al. Differential Expression of the hTERT Gene in Umbilical Cord-Derived Mesenchymal Stem Cells Cocultured with B Cell Precursor Leukemia Cell Microparticles or CD41+/CD61+ Platelet Microparticles. Biochem Genet (2023). https://doi.org/10.1007/s10528-023-10565-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10528-023-10565-9

Keywords

Navigation