Respiratory muscle paralysis due to trauma or neurodegenerative diseases can have devastating consequences. Only a few studies have investigated the reconstruction of motor function in denervated diaphragms caused by such conditions. Here, we studied the efficacy of transplanting E14 embryonic spinal motor neurons (SMNs) into peripheral nerve grafts for functionally reconstructing a denervated diaphragm in a rat model. The diaphragms of 8-week-old male Fischer 344 rats were first denervated by transecting the phrenic nerves. Subsequently, peripheral nerve grafts taken from the lower limb were used for neurotization of the denervated diaphragms. One week later, fetal E14 SMNs were transplanted into the peripheral nerve grafts. After 3 months, we observed functional contraction of the diaphragm following neuromuscular electrical stimulation (NMES) of the peripheral nerve graft. Additionally, we confirmed that SMN transplantation into the peripheral nerve graft had an inhibitory effect on diaphragm muscle atrophy. The SMNs transplanted into the peripheral nerve grafts formed a structure similar to the spinal cord, and the neuromuscular junction of the denervated diaphragm was reinnervated. These findings suggest the establishment of an ectopic motor neuron pool in the peripheral nerve graft. Free peripheral intra-nerve SMN transplantation in combination with NMES, which can be applied for diaphragmatic pacing, offers novel insights into the development of neuroregenerative therapies for treating life-threatening and intractable respiratory muscle paralysis caused by severe nerve damage and degenerative diseases.

Brachial plexus injuries (BPI), although rare, often results in significant morbidity. Stem cell was thought to be one of BPI treatment modalities because of their nerve-forming regeneration potential. Although there is a possibility for the use of mesenchymal stem cells as one of BPI treatment, it is still limited on animal studies. Therefore, this systematic review aimed to analyze the role of mesenchymal stem cells in nerve regeneration in animal models of brachial plexus injury.

This study is a systematic review with PROSPERO registration number CRD4202128321. Literature searching was conducted using keywords experimental, animal, brachial plexus injury, mesenchymal stem cell implantation, clinical outcomes, electrophysiological outcomes, and histologic outcomes. Searches were performed in the PubMed, Scopus, and ScienceDirect databases. The risk of bias was assessed using SYRCLE's risk of bias tool for animal studies. The data obtained were described and in-depth analysis was performed.

Four studies were included in this study involving 183 animals from different species those are rats and rabbits. There was an increase in muscle weight and shortened initial onset time of muscle contraction in the group treated with stem cells. Electrophysiological results showed that mesenchymal stem cells exhibited higher (Compound muscle action potential) CMAP amplitude and shorter CMAP latency than control but not better than autograft. Histological outcomes showed an increase in axon density, axon number, and the formation of connections between nerve cells and target muscles.

Mesenchymal stem cell implantation to animals with brachial plexus injury showed its ability to regenerate nerve cells as evidenced by clinical, electrophysiological, and histopathological results. However, this systematic study involved experimental animals from various species so that the results cannot be uniformed, and conclusion should be drawn cautiously.

Central nervous system (CNS) diseases are a leading cause of death and disability. Due to CNS neurons have no self-renewal and regenerative ability as they mature, their loss after injury or disease is irreversible and often leads to functional impairments. Unfortunately, therapeutic options for CNS diseases are still limited, and effective treatments for these notorious diseases are warranted to be explored. At present, stem cell therapy has emerged as a potential therapeutic strategy for improving the prognosis of CNS diseases. Accumulating preclinical and clinical evidences have demonstrated that multiple molecular mechanisms, such as cell replacement, immunoregulation and neurotrophic effect, underlie the use of stem cell therapy for CNS diseases. However, several issues have yet to be addressed to support its clinical application. Thus, this review article aims to summarize the role and underlying mechanisms of stem cell therapy in treating CNS diseases. And it is worthy of further evaluation for the potential therapeutic applications of stem cell treatment in CNS disease.