Mesenchymal stem/stromal cell-derived exosomes in regenerative medicine and cancer; overview of development, challenges, and opportunities

Abstract

Recently, mesenchymal stem/stromal cells (MSCs) and their widespread biomedical applications have attracted great consideration from the scientific community around the world. However, reports have shown that the main populations of the transplanted MSCs are trapped in the liver, spleen, and lung upon administration, highlighting the importance of the development of cell-free therapies. Concerning rising evidence suggesting that the beneficial effects of MSC therapy are closely linked to MSC-released components, predominantly MSC-derived exosomes, the development of an MSC-based cell-free approach is of paramount importance. The exosomes are nano-sized (30–100 nm) lipid bilayer membrane vesicles, which are typically released by MSCs and are found in different body fluids. They include various bioactive molecules, such as messenger RNA (mRNA), microRNAs, proteins, and bioactive lipids, thus showing pronounced therapeutic competence for tissues recovery through the maintenance of their endogenous stem cells, the enhancement of regenerative phenotypic traits, inhibition of apoptosis concomitant with immune modulation, and stimulation of the angiogenesis. Conversely, the specific roles of MSC exosomes in the treatment of various tumors remain challenging. The development and clinical application of novel MSC-based cell-free strategies can be supported by better understanding their mechanisms, classifying the subpopulation of exosomes, enhancing the conditions of cell culture and isolation, and increasing the production of exosomes along with engineering exosomes to deliver drugs and therapeutic molecules to the target sites. In the current review, we deliver a brief overview of MSC-derived exosome biogenesis, composition, and isolation methods and discuss recent investigation regarding the therapeutic potential of MSC exosomes in regenerative medicine accompanied by their double-edged sword role in cancer.

RETRACTED: Mesenchymal Stem/Stromal Cells as a Vehicle for Cytokine Delivery: An Emerging Approach for Tumor Immunotherapy

“…Human MSCs have demonstrated possible clinical utility for tumor therapy because of their inherent tumor tropism, making them promising carriers for antitumor drugs or molecules (17,(46)(47)(48). (18).…”

“…Besides, further knowledge of the specific molecular mechanisms complicated in the protumorigenic activities of MSCs is urgently required. Importantly, an alternative plan for using the intact MSCs for cytokine delivery is the utilizing MSC-derived conditioned medium, which potently attenuates the cell growth of MSCderived tumor cell (47,141,142).…”

Stem Cells and Exosomes: New Therapies for Intervertebral Disc Degeneration

“…Despite the promising results outlined above, there are still several limitations that need to be addressed before the use of stem cell-based therapies can be introduced as a standard treatment in the clinical setting. A primary concern with stem cell-based therapies is with the potential loss of cells and diminished viability upon administration [ 28 ]. Due to the biological and ethical concerns that arise with the use of stem cells, it would be difficult to justify repeated implantation, which could potentially be necessary if challenges associated with administration cannot be adequately addressed [ 23 ].…”

“…While initially considered a waste product, exosomes have recently been highlighted for their role in intercellular communication [ 25 , 26 ]. Exosomes show pronounced therapeutic competence for tissue regeneration through the maintenance of their endogenous stem cells, their ability to inhibit apoptosis and modulate the immune response, their enhancement of regenerative phenotypic traits, and stimulation of angiogenesis [ 27 , 28 ]. Stem cell-derived exosomes (SC-Exos), specifically, present a significant opportunity for the safe and effective treatment of IVDD because of their ability to maintain the therapeutic benefit of their origin cells without the risks associated with stem cell-based therapies [ 29 ].…”

Protective Effect of Adipose-Derived Mesenchymal Stem Cell Secretome against Hepatocyte Apoptosis Induced by Liver Ischemia-Reperfusion with Partial Hepatectomy Injury

“…The regenerative effects of transplanted stem cells are mainly attributed to the paracrine regulation of endogenous cells via secreted factors [ 25 ]. The secretome of a cell population refers to the biologically active factors secreted by the cells into the extracellular space, including soluble proteins, free nucleic acids, lipids, and extracellular vesicles [ 26 ], that aid in intercellular communication and transport.…”