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GMP-Compliant Mesenchymal Stem Cell-Derived Exosomes for Cell-Free Therapy in Cancer

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Stem Cells and Lineage Commitment

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2736))

Abstract

Cancer is categorized as one of the life-threatening disease in the world, which has recently been associated with a significant increase in the incidence and prevalence rate. Hence, the discovery of effective approaches for prevention, early diagnosis, and effective treatment for cancer has been prioritized by oncology researchers. In recent decades, mesenchymal stem cells show great potential to advance the field of regenerative medicine and oncology research due to representing prominent characteristics. Recently, studies indicate that mesenchymal stem cells can play an important role by secreting extracellular vesicles like exosomes in modulating the biological functions of target cells through paracrine regulation. Indeed, the exosomes derived from mesenchymal stem cells can represent the same therapeutic potential as parent cells with fewer side effects. Therefore, it can be demonstrated that exosomes can be a suitable drug delivery candidate in regenerative medicine and targeted therapy. It is also noteworthy that as the use of exosome therapy becomes more common in clinical studies, the importance of improving basic criteria such as safety, efficiency, and quality of stem cell products will also be highlighted. Based on this concept, the good manufacturing practice principles were put forward to examine the standard of cell products from different qualitative and quantitative aspects to progress the cell therapy. In other words, the principles of good manufacturing practice should be observed not only in the extraction and isolation of stem cells but also in the extraction of products related to stem cells such as exosomes in the field of treatment.

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Abbreviations

BSA:

Bovine serum albumin

CCM:

Cell culture conditioned media

CD:

Cluster of differentiation

CTRM:

Cell therapy and regenerative medicine

DMEM-LG:

Dulbecco Modified Eagle medium-low glucose

ECL:

Enhanced chemiluminescence

EDQM:

European Directorate for the Quality of Medicine & Healthcare

ELISA:

Enzyme-linked immunosorbent assay

EV:

Extracellular vesicle

FBS:

Fetal bovine serum

GMP:

Good manufacturing practice

hPLMSCs:

Human placenta-derived mesenchymal stem cells

HRP:

Horseradish peroxidase

MNCs:

Mononuclear cells

MSC-EXO:

Mesenchymal stem cell-derived exosome

MSCs:

Mesenchymal stem cells

PBS:

Phosphate-buffered saline

PCR:

Polymerase chain reaction

PVDF:

Polyvinylidene difluoride

QA:

Quality assurance

RNA:

Ribonucleic acid

RT:

Room temperature

SDS-PAGE:

Sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE)

SOP:

Standard operating procedure

TBST:

Tris-buffered saline with 0.1% Tween® 20 detergent

TEM:

Transmission electron microscope

TSEs:

Transmissible spongiform encephalopathies

References

  1. Arjmand B, Hamidpour SK, Alavi-Moghadam S et al (2022) Molecular docking as a therapeutic approach for targeting cancer stem cell metabolic processes. Front Pharmacol 13

    Google Scholar 

  2. Arjmand B, Hamidpour SK, Tayanloo-Beik A et al (2022) Machine learning: a new prospect in multi-omics data analysis of cancer. Front Genet 13:824451

    Article  PubMed  PubMed Central  Google Scholar 

  3. Rahim F, Arjmand B, Larijani B et al (2018) Stem cells treatment to combat Cancer and genetic disease: from stem cell therapy to gene-editing correction. In: Stem cells for cancer and genetic disease treatment, pp. 29–59. Springer

    Google Scholar 

  4. Arjmand B, Goodarzi P, Aghayan HR et al (2019) Co-transplantation of human fetal mesenchymal and hematopoietic stem cells in type 1 diabetic mice model. Front Endocrinol 10:761

    Article  Google Scholar 

  5. Larijani B, Aghayan H, Goodarzi P et al (2015) Clinical grade human adipose tissue-derived mesenchymal stem cell banking. Acta Med Iran 53:540–546

    PubMed  Google Scholar 

  6. Gilany K, Masroor MJ, Minai-Tehrani A et al (2019). Metabolic profiling of the mesenchymal stem cells’ secretome. In: Genomics, proteomics, and metabolomics, pp. 67–81. Springer

    Google Scholar 

  7. Abedi M, Alavi-Moghadam S, Payab M et al (2020) Mesenchymal stem cell as a novel approach to systemic sclerosis; current status and future perspectives. Cell Regen 9(1):1–19

    Article  Google Scholar 

  8. Derakhshanrad N, Saberi H, Meybodi KT et al (2015) Case report: combination therapy with mesenchymal stem cells and granulocyte-colony stimulating factor in a case of spinal cord injury. Basic Clin Neurosci 6(4):299

    PubMed  PubMed Central  Google Scholar 

  9. Larijani B, Arjmand B, Ahmadbeigi N et al (2015) A simple and cost-effective method for isolation and expansion of human fetal pancreas derived mesenchymal stem cells. Arch Iran Med 18(11)

    Google Scholar 

  10. Madani S, Setudeh A, Aghayan HR et al (2021) Placenta derived mesenchymal stem cells transplantation in type 1 diabetes: preliminary report of phase 1 clinical trial. J Diabetes Metab Disord 20(2):1179–1189

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Aghayan HR, Hosseini MS, Gholami M et al (2022) Mesenchymal stem cells’ seeded amniotic membrane as a tissue-engineered dressing for wound healing. Drug Deliv Transl Res 12(3):538–549

    Article  CAS  PubMed  Google Scholar 

  12. Goodarzi P, Alavi-Moghadam A, Sarvari M et al (2018) Adipose tissue-derived stromal cells for wound healing. In: Cell biology and translational medicine, volume 4, pp. 133–149. Springer

    Google Scholar 

  13. Pankajakshan D, Agrawal DK (2014) Mesenchymal stem cell paracrine factors in vascular repair and regeneration. J Biomed Technol Res 1(1):9

    Article  Google Scholar 

  14. Goodarzi P, Alavi-Moghadam S, Payab M et al (2019) Metabolomics analysis of mesenchymal stem cells. Int J Mol Cell Med 8(Suppl1):30

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Goodarzi P, Larijani B, Alavi-Moghadam S et al (2018) Mesenchymal stem cells-derived exosomes for wound regeneration. Cell Biol Transl Med 4:119–131

    Google Scholar 

  16. Soung YH, Ford S, Zhang V et al (2017) Exosomes in cancer diagnostics. Cancers 9(1):8

    Article  PubMed  PubMed Central  Google Scholar 

  17. Chen L, Wang L, Zhu L et al (2022) Exosomes as drug carriers in anti-cancer therapy. Front Cell Dev Biol 10:728616

    Article  PubMed  PubMed Central  Google Scholar 

  18. Shen M, Chen T (2021) Mesenchymal stem cell-derived exosomes and their potential agents in hematological diseases. Oxid Med Cell Longev 2021:4539453

    Article  PubMed  PubMed Central  Google Scholar 

  19. Roşca AM, Ţuţuianu R, Titorencu ID (2018) Mesenchymal stromal cells derived exosomes as tools for chronic wound healing therapy. Romanian J Morphol Embryol 59(3):655–662

    Google Scholar 

  20. Sun S-J, Wei R, Li F et al (2021) Mesenchymal stromal cell-derived exosomes in cardiac regeneration and repair. Stem Cell Reports 16(7):1662–1673

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Shokravi S, Borisov V, Zaman BA et al (2022) Mesenchymal stromal cells (MSCs) and their exosome in acute liver failure (ALF): a comprehensive review. Stem Cell Res Ther 13(1):1–21

    Article  Google Scholar 

  22. Cao Q, Huang C, Chen X-M et al (2022) Mesenchymal stem cell-derived exosomes: toward cell-free therapeutic strategies in chronic kidney disease. Front Med 9:23

    Article  Google Scholar 

  23. Chen Y-S, Lin E-Y, Chiou T-W et al (2020) Exosomes in clinical trial and their production in compliance with good manufacturing practice. Tzu-Chi Med J 32(2):113

    Article  CAS  Google Scholar 

  24. Aghayan H-R, Goodarzi P, Arjmand B (2014) GMP-compliant human adipose tissue-derived mesenchymal stem cells for cellular therapy. In: Stem cells and good manufacturing practices, pp. 93–107. Springer

    Google Scholar 

  25. Aghayan HR, Payab M, Mohamadi-Jahani F et al (2020). GMP-compliant production of human placenta-derived mesenchymal stem cells. In: Stem cells and good manufacturing practices, pp. 213–225. Springer

    Google Scholar 

  26. Larijani B, Aghayan H-R, Goodarzi P et al (2014) GMP-grade human fetal liver-derived mesenchymal stem cells for clinical transplantation. In: Stem cells and good manufacturing practices, pp. 123–136. Springer

    Google Scholar 

  27. Ebrahimi-Barough S, Ai J, Payab M et al (2020) Standard operating procedure for the good manufacturing practice-compliant production of human endometrial stem cells for multiple sclerosis. In: Stem cells and good manufacturing practices, pp. 199–212. Springer

    Google Scholar 

  28. International B (2022). https://www.biopharminternational.com/view/considerations-for-us-fetal-bovine-serum-sourcing

  29. Arjmand B, Goodarzi P, Alavi-Moghadam S et al (2020) GMP-compliant human schwann cell manufacturing for clinical application. In: Stem cells and good manufacturing practices, pp. 227–235. Springer

    Google Scholar 

  30. Aghayan HR, Arjmand B, Burger SR (2016) GMP facilities for clinical cell therapy product manufacturing: a brief review of requirements and design considerations. Perinatal Tissue-Derived Stem Cells: 215–227

    Google Scholar 

  31. Arabi M, Mohamadi-Jahani F, Alavi-Moghadam S et al (2020) Standards and regulatory frameworks (for cell-and tissue-based products). In: Biomedical product development: bench to bedside, pp. 89–97. Springer

    Google Scholar 

  32. Arjmand B, Alavi-Moghadam S, Payab M et al (2020) GMP-compliant adenoviral vectors for gene therapy. In: Stem cells and good manufacturing practices, pp. 237–250. Springer

    Google Scholar 

  33. Pawar SD, Khare AB, Keng SS (2021) Selection and application of biological safety cabinets in diagnostic and research laboratories with special emphasis on COVID-19. Rev Sci Instr 92(8):081401. https://doi.org/10.1063/5.0047716

    Article  CAS  Google Scholar 

  34. Blajchman M (2000) Reducing the risk of bacterial contamination of cellular blood components. Dev Biol 102:183–193

    CAS  Google Scholar 

  35. Langdon SP (2004) Cell culture contamination. Cancer Cell Culture 88:309–317

    Article  Google Scholar 

  36. Lincoln CK, Gabridge MG (1998) Cell culture contamination: sources, consequences, prevention, and elimination. Methods Cell Biol 57:49–65

    Article  CAS  PubMed  Google Scholar 

  37. Long EG, Buluk M, Gallagher MB et al (2019) Human mesenchymal stem cell morphology, migration, and differentiation on micro and nano-textured titanium. Bioact Mater 4:249–255. https://doi.org/10.1016/j.bioactmat.2019.08.001

    Article  PubMed  PubMed Central  Google Scholar 

  38. Akyar I (2012) Standard operating procedures (what are they good for?). In: Latest research into quality control, pp. 367–391

    Google Scholar 

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Author information

Authors and Affiliations

  1. Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Babak Arjmand, Sepideh Alavi-Moghadam, Shayesteh Kokabi-Hamidpour & Rasta Arjmand

  2. Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Mostafa Rezaei-Tavirani

  3. Integrative Oncology Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran

    Kambiz Gilany

  4. Reproductive Immunology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran

    Kambiz Gilany

  5. AJA Cancer Epidemiology Research and Treatment Center (AJA-CERTC), AJA University of Medical Sciences, Tehran, Iran

    Mohsen Rajaeinejad

  6. Health Research Institute, Thalassemia and Hemoglobinopathies Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Fakher Rahim

  7. Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Nazli Namazi

  8. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical sciences, Tehran, Iran

    Bagher Larijani

Authors
  1. Babak Arjmand
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  2. Sepideh Alavi-Moghadam
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  3. Mostafa Rezaei-Tavirani
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  4. Shayesteh Kokabi-Hamidpour
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  5. Rasta Arjmand
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  6. Kambiz Gilany
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  7. Mohsen Rajaeinejad
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  8. Fakher Rahim
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  9. Nazli Namazi
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  10. Bagher Larijani
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Corresponding author

Correspondence to Babak Arjmand .

Editor information

Editors and Affiliations

  1. Ottawa, ON, Canada

    Kursad Turksen

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Arjmand, B. et al. (2023). GMP-Compliant Mesenchymal Stem Cell-Derived Exosomes for Cell-Free Therapy in Cancer. In: Turksen, K. (eds) Stem Cells and Lineage Commitment. Methods in Molecular Biology, vol 2736. Humana, New York, NY. https://doi.org/10.1007/7651_2022_467

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  • DOI: https://doi.org/10.1007/7651_2022_467

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-3536-0

  • Online ISBN: 978-1-0716-3537-7

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