Rat Bone Mesenchymal Stem Cell‐Derived Exosomes Loaded with miR‐494 Promoting Neurofilament Regeneration and Behavioral Function Recovery after Spinal Cord Injury

Abstract

Exosomes (Exo) exhibit numerous advantages (e.g., good encapsulation, high targeting efficiency, and easy to penetrate the blood-brain barrier to the central nervous system). Exosomes are recognized as prominent carriers of mRNAs, siRNAs, miRNAs, proteins, and other bioactive molecules. As confirmed by existing studies, miR-494 is important to regulate the occurrence, progression, and repair of spinal cord injury (SCI). We constructed miR-494-modified exosomes (Exo-miR-494). As indicated from related research in vitro and vivo, Exo-miR-494 is capable of effectively inhibiting the inflammatory response and neuronal apoptosis in the injured area, as well as upregulating various anti-inflammatory factors and miR-494 to protect neurons. Moreover, it can promote the regeneration of the neurofilament and improve the recovery of behavioral function of SCI rats.

Therapeutic Effect of Exosomes Derived From Stem Cells in Spinal Cord Injury: A Systematic Review Based on Animal Studies

“…A total of 701 related articles were obtained. After excluding the literature based on the exclusion criteria, eventually 32 studies were included ( 19 – 21 , 28 – 56 ). The entire screening process is summarized in Figure 1 .…”

“…Among the included 32 studies, only two studies were controlled studies ( 29 , 33 ), and the remaining 30 studies were randomized controlled studies. The species of animals included SD rats ( 19 – 21 , 28 – 37 , 39 , 40 , 42 – 44 , 46 , 47 , 49 – 53 , 55 , 56 ), Wistar rats ( 41 , 54 ), and C57BL/6 mice ( 38 , 45 , 48 ); gender included male ( 28 , 30 – 32 , 38 – 45 , 49 , 53 , 54 ) and female ( 19 , 20 , 29 , 33 , 34 , 36 , 37 , 46 – 48 , 50 – 52 , 55 , 56 ), two studies did not report the sex of the animals ( 21 , 35 ); the weights of animals were between 150 ( 41 ) and 300 g ( 20 , 44 ), the weight of the mouse was between 17 and 22 g ( 48 ), and seven of the studies did not report the weight of the animals ( 21 , 29 , 30 , 38 , 42 , 45 , 50 ); age was between 6 ( 38 , 44 , 45 , 50 , 51 ) and 12 weeks ( 47 , 56 ), and nine of the studies did not report the age of the animals ( …”

“…Six studies reported types of exosomes but did not report specific sources ( 31 , 32 , 38 , 40 , 45 , 46 ). The transplantation route of exosomes included tail vein ( 19 – 21 , 29 – 32 , 34 – 50 , 52 – 56 ), intranasally ( 33 ) and subcutaneous ( 51 ), and one study did not report the route of exosome transplantation ( 28 ); the time transplantation of exosome ranged from 0 ( 19 , 20 , 31 , 38 , 41 , 44 – 47 , 49 ) to 24 h ( 42 , 43 ) after modeling, one study did not report the time of exosome transplantation ( 40 ); dose of exosomes ranged from 20 ( 29 ) to 200 μg ( 28 , 30 – 33 , 36 – 38 , 41 , 43 , 45 – 49 , 53 , 56 ); the control group includes PBS ( 19 – 21 , 28 – 32 , 34 , 35 , 38 , 39 , 41 , 43 – 51 , 53 – 56 ), saline ( 33 , 36 , 37 , 40 , 42 ), and blank ( 52 ). Basic information of the study subjects was summarized in Supplementary Table 2 .…”

“…Among the included 32 studies, only two studies were controlled studies (29,33), and the remaining 30 studies were randomized controlled studies. The species of animals included SD rats (19-21, 28-37, 39, 40, 42-44, 46, 47, 49-53, 55, 56), Wistar rats (41,54), and C57BL/6 mice (38,45,48); gender included male (28, 30-32, 38-45, 49, 53, 54) and female (19, 20, 29, 33, 34, 36, 37, 46-48, 50-52, 55, 56), two studies did not report the sex of the animals (21,35); the weights of animals were between 150 (41) and 300 g (20,44), the weight of the mouse was between 17 and 22 g ( 48), and seven of the studies did not report the weight of the animals (21,29,30,38,42,45,50); age was between 6 (38,44,45,50,51) and 12 weeks (47, 56), and nine of the studies did not report the age of the animals (19, 21, 35-37, 42, 46, 51, 52); samples size were between 10 (51) and 100 (41); models of SCI included contusion (20, 21, 28-32, 34-53, 56), hemisection (54), and transection (19,33,55); the types of exosomes included the exosomes of bone marrow mesenchymal stem cells of SD rats (BMSCs-Exo) (20, 21, 28, 30, 34-37, 39, 42-44, 47, 49, 52, 53, 56), BMSCs-Exo of Wistar rats (41,54), BMSCs-Exo of human (19,33,…”

“…For example, Huang et al tracked exosomes through an animal imaging system and found that most of the exosomes still gather in the liver and lungs, and are finally swallowed by monocytes. In fact, only a limited number of exosomes reach the spinal cord ( 20 , 21 ). However, Chen et al reported that exosomes are much smaller than stem cells and are easily accessible through the blood-brain barrier without being captured by liver or lung tissue ( 22 ).…”