Stem Cells and Exosomes-associated Therapeutic Applications
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Keywords

Stem cells
Exosomes
Therapeutic
Cancer
Parkinson
Diabetes

DOI

10.26689/jcnr.v8i6.7012

Submitted : 2024-06-18
Accepted : 2024-07-03
Published : 2024-07-18

Abstract

Exosomes are extracellular vesicles with sizes from 30 to 150 nm in diameter and modulate the transport of multiple intracellular biological molecules including proteins, nucleic acids, lipids, and metabolites. They regulate a large number of cells and are involved in different pathological and physiological activities including carcinogenesis, viral infection, cell-cell communication and immune responses as well. Stem cell-derived exosomes carry many benefits over simple stem cells in the form of easy access, freedom from tumourigenic capabilities, non-infusion toxicity, effortless preservation, and immunogenicity. Exosomes have almost the same properties and perform functions effectively in the same way as their parental cells do like adult stem cells and embryonic stem cells. Due to their pluripotent or multipotent abilities, stem cells (SCs) transform into several types of cells. In addition to other secretions, SC also give exosomes, which in turn shows therapeutic significance for many disorders, including cancer, diabetes mellitus, skin allergies and regenerative medicine. Exosomes originating from mesenchymal stem cells (MSCs) have miRNAs, lipids, and proteins that trigger diabetes and cancer situations in humans. Exosomes from SCs (sc-exos) are preferred to SC as there are fewer side effects and other challenges, including effectiveness, drug delivery, lower immunogenicity and tumourigenicity. In the current review, we summarize the data from the last 5 years’ articles about exosomes and stem cell-derived microvesicles for the therapeutic potential of various diseases such as cancer, Alzheimer’s disease, diabetes, and Parkinson’s disease with clinical challenges and future aspects.

References

Dilsiz N, 2022, Hallmarks of Exosomes. Future Science OA, 8(1): FSO764.

Kok VC, Yu CC, 2020, Cancer-derived Exosomes: Their Role in Cancer Biology and Biomarker Development. International Journal of Nanomedicine, 2020(15): 8019–8036.

Malekian F, Shamsian A, Kodam SP, et al., Exosome Engineering for Efficient and Targeted drug Delivery: Current Status and Future Perspective. The Journal of Physiology, 601(22): 4853–4872.

Huda MN, Nafiujjaman M, Deaguero IG, et al., 2021, Potential Use of Exosomes as Diagnostic Biomarkers and in Targeted Drug Delivery: Progress in Clinical and Preclinical Applications. ACS Biomaterials Science & Engineering, 7(6): 2106–2149.

Ebrahimi A, Ahmadi H, Ghasrodashti ZP, et al., 2021, Therapeutic Effects of Stem Cells in Different Body Systems A Novel Method That is Yet to Gain Trust: A Comprehensive Review. Bosnian Journal of Basic Medical Sciences, 21(6): 672.

Ung TH, Madsen HJ, Hellwinkel JE, et al., 2014, Exosome Proteomics Reveals Transcriptional Regulator Proteins with Potential to Mediate Downstream Pathways. Cancer Science, 105(11): 1384–1392.

Ma CY, Zhai Y, Li CT, et al., 2024, Translating Mesenchymal Stem Cell and Their Exosome Research into GMP Compliant Advanced Therapy Products: Promises, Problems and Prospects. Medicinal Research Reviews, 44(3): 919–938.

Peng X, Yang L, Ma Y, et al., 2020, Focus on the Morphogenesis, Fate and the Role in Tumour Progression of Multivesicular Bodies. Cell Communication and Signaling, 18(122): 1–15.

Hu S, Li Y, Shen J, 2020, A Diverse Membrane Interaction Network for Plant Multivesicular Bodies: Roles in Proteins Vacuolar Delivery and Unconventional Secretion. Frontiers in Plant Science, 11(425): 525631.

Pavlic A, Bahram Sangani N, Kerins J, et al., 2022, Vascular Smooth Muscle Cell Neutral Sphingomyelinase 2 in the Release of Exosomes and Vascular Calcification. International Journal of Molecular Sciences, 23(16): 9178.

Fu S, Wang Y, Xia X, et al., 2020, Exosome Engineering: Current Progress in Cargo Loading and Targeted Delivery. NanoImpact, 20(1): 100261.

Kuo IY, Hsieh CH, Kuo WT, et al., 2022, Recent Advances in Conventional and Unconventional Vesicular Secretion Pathways in the Tumour Microenvironment. Journal of Biomedical Science, 29(1): 56.

Sharma S, Sharma U, 2022, Exosomes in Cardiovascular Diseases: A Blessing or a Sin for the Mankind. Molecular and Cellular Biochemistry, 477(3): 833–847.

Duan L, Xu X, Xu L, et al., 2021, Exosome-mediated Drug Delivery for Cell-free Therapy of Osteoarthritis. Current Medicinal Chemistry, 28(31), 6458–6483.

Bakhsh T, Alhazmi S, Alburae NA, et al., 2022, Exosomal miRNAs as a Promising Source of Biomarkers in Colorectal Cancer Progression. International Journal of Molecular Sciences, 23(9): 4855.

Abdulmalek OAAY, Husain KH, AlKhalifa HKAA, et al., 2024, Therapeutic Applications of Stem Cell-Derived Exosomes. International Journal of Molecular Sciences, 25(6): 3562.

Levy D, Jeyaram A, Born LJ, et al., Impact of Storage Conditions and Duration on Function of Native and Cargo-loaded Mesenchymal Stromal Cell Extracellular Vesicles. Cytotherapy, 25(5): 502–509.

Mettlen M, Chen PH, Srinivasan S, et al., 2018, Regulation of Clathrin-mediated Endocytosis. Annual Review of Biochemistry, 2018(87): 871–896.

Lau NCH, Yam JWP, 2023, From Exosome Biogenesis to Absorption: Key Takeaways for Cancer Research. Cancers, 15(7): 1992.

Engin A, 2021, Dark-side of Exosomes. Protein Kinase-mediated Decisions Between Life and Death, 101–131.

Hade MD, Suire CN, Suo Z, 2021, Mesenchymal Stem Cell-derived Exosomes: Applications in Regenerative Medicine. Cells, 10(8): 1959.

Kang J, Li Z, Zhi Z, et al., 2019, MiR-21 Derived from the Exosomes of MSCs Regulates the Death and Differentiation of Neurons in Patients with Spinal Cord Injury. Gene Therapy, 26(12): 491–503.

Shukla L, Yuan Y, Shayan R, 2020, Fat Therapeutics: The Clinical Capacity of Adipose-derived Stem Cells and Exosomes for Human Disease and Tissue Regeneration. Frontiers in Pharmacology, 2020(11): 158.

Yang Y, Qin M, Bao P, et al., 2017, Secretory Carrier Membrane Protein 5 is an Autophagy Inhibitor that Promotes the Secretion of alpha-synuclein via Exosome. PloS One, 12(7): e180892.

Guo J, Yang X, Chen J, et al., 2023, Exosomal miR-125b-5p Derived from Adipose-derived Mesenchymal Stem Cells Enhance Diabetic Hindlimb Ischemia Repair via Targeting Alkaline Ceramidase 2. Journal of Nanobiotechnology, 21(1): 189.

Wan R, Hussain A, Behfar A, 2022, The Therapeutic Potential of Exosomes in Soft Tissue Repair and Regeneration. International Journal of Molecular Sciences, 23(7): 3869.

Li Z, Mu D, Liu C, et al., 2022, The Impact of Ammonium Chloride-Based Erythrocyte Lysis Process on Banked Adipose-Derived Stem Cells. Biopreservation and Biobanking, 20(3): 229–237.

Lei B, Wu X, Xia K, et al., 2021, Exosomal MicroRNA-96 Derived From Bone Marrow Mesenchymal Stem Cells Inhibits Doxorubicin-Induced Myocardial Toxicity by Inhibiting the Rac1/Nuclear Factor-KappaB Signaling Pathway. Journal of the American Heart Association, 10(17): e020589.

Zeng H, Yang Y, Tou F, et al., 2023, Bone Marrow Stromal Cell-derived Exosomes Improve Oxidative Stress and Pyroptosis in Doxorubicin-induced Myocardial Injury in vitro by Regulating the Transcription of GSDMD through the PI3K-AKT-Foxo1 Pathway. Immunity, Inflammation and Disease, 11(3): e810.

Han JW, Yoon JS, 2011, Induced Pluripotent Stem Cells: Emerging Techniques for Nuclear Reprogramming. Antioxidants & Redox Signaling, 15(7): 1799–1820.

Tian Z, Guo F, Biswas S, et al., 2016, Rationale and Methodology of Reprogramming for Generation of Induced Pluripotent Stem Cells and Induced Neural Progenitor Cells. International Journal of Molecular Sciences, 17(4): 594.

Gaglani S, Gonzalez-Kozlova E, Lundon DJ, et al., 2021, Exosomes as a Next-generation Diagnostic and Therapeutic Tool in Prostate Cancer. International Journal of Molecular Sciences, 22(18): 10131.

Li L, Zhang L, Montgomery KC, et al., 2023, Advanced Technologies for Molecular Diagnosis of Cancer: State of Pre-clinical Tumour-derived Exosome Liquid Biopsies. Materials Today Bio, 18(1): 100538.

Makler A, Asghar W, 2020, Exosomal Biomarkers for Cancer Diagnosis and Patient Monitoring. Expert Review of Molecular Diagnostics, 20(4): 387–400.

Yang L, Shi P, Zhao G, et al., 2020, Targeting Cancer Stem Cell Pathways for Cancer Therapy. Signal Transduction and Targeted Therapy, 5(1): 8.

Jiao YR, Chen KX, Tang X, et al., 2024, Exosomes Derived from Mesenchymal Stem Cells in Diabetes and Diabetic Complications. Cell Death & Disease, 15(4): 271.

Cai H, Guo H, 2023, Mesenchymal Stem Cells and Their Exocytotic Vesicles. International Journal of Molecular Sciences, 24(3): 2085.

Ocansey DKW, Zhang L, Wang Y, et al., 2020, Exosome-mediated Effects and Applications in Inflammatory Bowel Disease. Biological Reviews, 95(5): 1287–1307.

Li X, Cao Y, Xu X, et al., 2023, Sleep Deprivation Promotes Endothelial Inflammation and Atherogenesis by Reducing Exosomal miR-182-5p. Arteriosclerosis, Thrombosis, and Vascular Biology, 43(6): 995–1014.

Zhou Y, Zhao B, Zhang XL, et al., 2021, Combined Topical and Systemic Administration with Human Adipose-derived Mesenchymal Stem Cells (hADSC) and hADSC-derived Exosomes Markedly Promoted Cutaneous Wound Healing and Regeneration. Stem Cell Research & Therapy, 12(1): 257.

An Y, Lin S, Tan X, et al., 2021, Exosomes from Adipose-derived Stem Cells and Application to Skin Wound Healing. Cell Proliferation, 54(3): 12993.

Wang J, Wang J, Li X, et al., 2022, Cell-derived Exosomes as Therapeutic Strategies and Exosome-derived microRNAs as Biomarkers for Traumatic Brain Injury. Journal of Clinical Medicine, 11(11): 3223.

Wang J, Sun X, Zhao J, et al., 2017, Exosomes: A Novel Strategy for Treatment and Prevention of Diseases. Frontiers in Pharmacology, 8(1): 1–13.

Li J, Gao H, Xiong Y, et al., 2022, Enhancing Cutaneous Wound Healing Based on Human Induced Neural Stem Cell-derived Exosomes. International Journal of Nanomedicine, 17(1): 5991–6006.

Huber CC, Callegari EA, Paez MD, et al., 2022, Heat Shock-induced Extracellular Vesicles Derived from Neural Stem Cells Confer Marked Neuroprotection Against Oxidative Stress and Amyloid-Beta-Caused Neurotoxicity. Molecular Neurobiology, 59(12): 7404–7412.

Chen YA, Lu CH, Ke CC, et al., 2021, Mesenchymal Stem Cell-derived Exosomes Ameliorate Alzheimer’s Disease Pathology and Improve Cognitive Deficits. Biomedicines, 9(6): 594.

Hernandez-Sapiens MA, Reza-Zaldivar EE, Cevallos RR, et al., 2020, A Three-dimensional Alzheimer’s Disease Cell Culture Model Using iPSC-derived Neurons Carrying A246E Mutation in PSEN1. Frontiers in Cellular Neuroscience, 14(1): 1–11.