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Review
. 2024 Mar 21;25(6):3562.
doi: 10.3390/ijms25063562.

Therapeutic Applications of Stem Cell-Derived Exosomes

Omar Abdulhakeem Ahmed Yusuf Abdulmalek  1 , Khaled Hameed Husain  1 , Haya Khaled Ali Abdulla AlKhalifa  1 , Mariam Masood Abdulkarim Bahrooz Alturani  1 , Alexandra E Butler  2 , Abu Saleh Md Moin  2
Affiliations
Review

Therapeutic Applications of Stem Cell-Derived Exosomes

Omar Abdulhakeem Ahmed Yusuf Abdulmalek et al. Int J Mol Sci. .

Abstract

Exosomes are extracellular vesicles of endosomal origin, ranging from 30 to 150 nm in diameter, that mediate intercellular transfer of various biomolecules, such as proteins, lipids, nucleic acids, and metabolites. They modulate the functions of recipient cells and participate in diverse physiological and pathological processes, such as immune responses, cell-cell communication, carcinogenesis, and viral infection. Stem cells (SCs) are pluripotent or multipotent cells that can differentiate into various cell types. SCs can also secrete exosomes, which exhibit remarkable therapeutic potential for various diseases, especially in the field of regenerative medicine. For example, exosomes derived from mesenchymal stem cells (MSCs) contain proteins, lipids, and miRNAs that can ameliorate endocrine disorders, such as diabetes and cancer. Exosomes from SCs (sc-exos) may offer similar advantages as SCs, but with reduced risks and challenges. Sc-exos have lower tumorigenicity, immunogenicity, and infectivity. They can also deliver drugs more efficiently and penetrate deeper into tissues. In this review, we provide an overview of the recent advances in sc-exos and their therapeutic applications in various diseases, such as diabetes and cancer. We also elucidate how the biological effects of sc-exos depend on their molecular composition. We also address the current challenges and future directions of using sc-exos.

Keywords: diabetic microvascular complications; exosomes; microRNAs; precision medicine; stem cells.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Biogenesis of exosomes. The chart depicts the transformation of endosomes into early-sorting endosomes (ESEs) (Step 1), their progression to late-sorting endosomes (LSEs) (Step 2), and the subsequent journey through the Endosomal Sorting Complex Required for Transport (ESCRT) and ESCRT-independent pathways to form multivesicular bodies (MVBs) (Step 3). Subsequently, with the assistance of Ras-related protein Rab-27A (RAB27A) and RAB27B, they are transported along microtubules for exocytosis (Step 4). These exosomes typically comprise Cluster of Differentiation (CD)63, CD81, CD9, DNA fragments, messenger RNA (mRNA), microRNA (miRNA), proteins, molecules and other components.
Figure 2
Figure 2
Comprehensive Flowchart of Exosome Production from stem cells. Beginning with tissue biopsy and proceeding through stem cell identification, cultivation, exosome induction, purification, characterization, and concluding with storage preparation for therapeutic or diagnostic applications. TEM: transmission electron microscopy; NTA: nanoparticle tracking analysis.
Figure 3
Figure 3
Therapeutic applications of MSC-exos in diabetes treatment and its microvascular complications. MSC-exos can be used to modulate a wide range of diabetes manifestations, including: pancreatic beta cell function and insulin sensitivity; diabetic retinopathy; diabetic nephropathy; and diabetic neuropathy. MSC-exos: mesenchymal stem cell-derived exosomes; T1D: type 1 diabetes mellitus; miR: microRNA. Upward green arrows indicate positive modulation and downward red arrows indicate negative modulation, respectively.
Figure 4
Figure 4
Therapeutic applications of MSC-exos in cancer treatment. The applications of MSC-exos for cancer can be broadly divided into 3 categories: to enhance chemosensitivity, to deliver drugs, and as a direct therapeutic agent via its miRNA cargo. Upward green arrow indicate positive modulation. Downward red arrows indicate negative modulation. MSC-exos: mesenchymal stem cell-derived exosomes; miR: micro-RNA; HCC: hepatocellular carcinoma; Cho: cholesterol-modified; RHPN2: rhophilin Rho GTPase binding protein 2; TRIM59: tripartite motif containing 59. Green arrows indicate the modulation of the respective pathways.
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This research received no external funding.