## 3 Therapeutic Potential of Exosomes in Different Diseases
### Therapeutic Potential of Exosomes in Neural Diseases  
Peripheral nerve injury (PNI) is a well-known neurological disorder that adversely affects human health. It affects about 2.8%-5% of patients with polytrauma resulting in sensory-motor dysfunction [80]. Many factors such as immune cell deposition and conversion of Schwann cell (SC) phenotypes lead to axonal development following PNI. It is estimated that the daily growth of regenerating axons is only 1 mm, which could be difficult to manage clinically [81]. Additionally, proximal nerves extended denaturation may prolong the possibility of nervous organ irreversible atrophy [82]. Furthermore, nerve tissue damage associated with PNI increases the complexity of nerve regeneration [83; 84]. Although the gold standard in the management of PNI is the transplantation of autologous nerves, this technique is rarely performed because there is a shortage of donor sources and possible neurological damage to the donor site [85]. Many studies have incorporated new techniques for starting axon rejuvenation without sacrificing the functions of healthy nerves. Another approach is to use synthetic nerve ducts with numerous stem cells that can be beneficial, but the results are far from ideal [86]. Interestingly, another strategy for the management of peripheral nerve regeneration is the use of exosomes derived from MSC. Another study examined MSC use by modifying them to increase bioactive molecular levels which will promote PNI recovery. Furthermore, the in vitro internalization of MSC exosomes by SCs leads to a significant increase in SC proliferation and subsequently leading to axonal regeneration [87]. The nerve growth factor (NGF), fibroblast growth factor-1 (FGF-1), glial cell-derived neurotrophic factor (GDNF), insulin-like growth factor-1 (IGF-1), and brain-derived neurotrophic factor (BDNF) are some of the multiple neurotrophic causes of MSC exosomes. Nevertheless, MSC exosomes have beneficial effects which include promoting recovery from neural survival,ervation muscle atrophy, and axonal development by the use of bioactive molecules [88]. It has been demonstrated previously that axonal regeneration is controlled by macrophages and not by SCs [89]. Immune cells, primarily phagocytic neutrophils, and macrophages are the first to migrate to the degenerative site within hours or days after peripheral nerve damage, whether caused by a neurological disorder or infection. The critical role of neuroinflammation in PNI recovery cannot be overemphasized, and it starts with a process called Wallerian degeneration (WD). In this process, myelinating SCs undergo differentiation and are mainly seen in the distal portion of the nerve [90]. Thereafter, proinflammatory cytokines and chemokines are produced by differentiated SCs resulting in activation of the neuroinflammationary event. Neuroinflammatory response leads to the hiring of peripheral immune cells and circulating macrophages to the affected site [91]. The combination of resident and circulating macrophages activate the clearance of axonal debris and myelin. It is worthwhile to note here that damaged axons must be cleared of debris and myelin because they contain molecules that exert an inhibitory effect on the development of axons, most especially at the late stages of WD [92]. At the distal stump and neuronal cell body, macrophages and other phagocytic cells precipitate to promote lesion response which is the mechanism adopted by neurons to activate regeneration. Nonetheless, neuroinflammation is a double-edged sword in this scenario as it is a critical response for nerve regeneration, but the excess of it prevents nerve regeneration as well as the incorporation of pain in the neuropathic events. An important goal in PNI management is the creation of a microenvironment allowing a reasonable level of inflammation and regeneration [93]. During peripheral nerve repair, the rebuilding of the vascular network is a vital microenvironment that promotes regeneration and axonal development.