Application of mesenchymal stem cell-derived exosomes from different sources in intervertebral disc degeneration

Abstract

Intervertebral disc degeneration (IVDD) is a main cause of lower back pain, leading to psychological and economic burdens to patients. Physical therapy only delays pain in patients but cannot eliminate the cause of IVDD. Surgery is required when the patient cannot tolerate pain or has severe neurological symptoms. Although surgical resection of IVD or decompression of the laminae eliminates the diseased segment, it damages adjacent normal IVD. There is also a risk of re-protrusion after IVD removal. Cell therapy has played a crucial role in the development of regenerative medicine. Cell transplantation promotes regeneration of degenerative tissue. However, owing to the lack of vascular structure in IVD, sufficient nutrients cannot be provided for transplanted mesenchymal stem cells (MSCs). In addition, dead cells release harmful substances that aggravate IVDD. Extracellular vesicles (EVs) have been extensively studied as an emerging therapeutic approach. EVs generated by paracrine MSCs retain the potential of MSCs and serve as carriers to deliver their contents to target cells to regulate target cell activity. Owing to their double-layered membrane structure, EVs have a low immunogenicity and no immune rejection. Therefore, EVs are considered an emerging therapeutic modality in IVDD. However, they are limited by mass production and low loading rates. In this review, the structure of IVD and advantages of EVs are introduced, and the application of MSC-EVs in IVDD is discussed. The current limitations of EVs and future applications are described.

Mesenchymal stem cells in the treatment of spinal cord injury: Mechanisms, current advances and future challenges

“…MSCs derive from a wide range of sources and have selfproliferation and multidirectional differentiation capabilities (37). MSCs are widely used in cell therapy and regenerative medicine because of their immunomodulatory and tissue repair effects (5,38). MSCs can be isolated from almost all tissues, including bone marrow, adipose tissue, amniotic fluid, umbilical cord, liver, and heart (39).…”

“…Regenerative medicine strategies based on cell therapy have attracted interest in recent years (5). Mesenchymal stem cells (MSCs) have the ability to differentiate and self-proliferate, and there has been an increasing focus on their use as potential therapeutic agents for a variety of diseases.…”

Extracellular vesicles and their cells of origin: Open issues in autoimmune diseases

“…MSC-EVs, like their original cell sources (MSCs), are believed to have low immunogenicity as well as lower carcinogenic risk ( 178 ). They do not release certain inflammatory factors (IL-1, IL-6, and IL-8), which may be vastly released from dead cells following cell injection procedures, especially in tissues lacking adequate blood/nutrients ( 179 ). In addition, EVs demonstrate enhanced circulation stability due to the immune system’s evasion ( 39 ).…”

Biomaterials delivery strategies to repair spinal cord injury by modulating macrophage phenotypes

“…Mesenchymal stem cells secrete anti-inflammatory factors to reduce the inflammatory response around injury. 101 Mesenchymal stem cells (MSCs) exhibit major autocrine and paracrine activities that stimulate the proliferation and differentiation of other cells and themselves. 93 Transplantation of mesenchymal stem cells into an injured area results in increased numbers of M2 macrophages and decreased M1 cells.…”

“… 106 With the development of tissue engineering and regenerative medicine, extracellular vesicles (EVs) have made great progress as active biological substances for intercellular communication due to their ability to promote tissue regeneration. 101 The paracrine-derived EVs of hMSCs have been reported in many preclinical models. 102 Liu et al used Mel to pretreat hMSCs to generate EVs, before using Evs and Mel to form a delivery system (MEV) to deliver Mel to the SCI site for continuous release.…”