Abstract
Severe peripheral nerve injury, which does not promise natural healing, inevitably requires clinical treatment. Here, we demonstrated the facilitation effect of peripheral nerve regeneration using a cytokine cocktail secreted by skeletal muscle-derived stem cells (Sk-MSCs). Mouse sciatic nerve was transected with a 6 mm gap and bridged collagen tube, and the culture supernatant of Sk-MSCs with 20% adult mouse serum (AMS)/Iscove’s modified Dulbecco’s medium (IMDM) was administered into the tube immediately after the operation, followed by an injection once a week for six weeks through the skin to the surrounding tube of the cytokine (CT) group. Similarly, 20% AMS/IMDM without cytokines was administered to the non-cytokine control (NT) group. Tension recovery in the plantar flexor muscles via electrical stimulation at the upper portion of the damaged nerve site, as well as the numerical recovery of axons and myelinated fibers at the damaged site, were evaluated as an index of nerve regeneration. Specific cytokines secreted by Sk-MSCs were compared with damaged sciatic nerve-derived cytokines. Six weeks after operation, significantly higher tension output and numerical recovery of the axon and myelinated fibers were consistently observed in the CT group, showing that the present cytokine cocktail may be a useful nerve regeneration acceleration agent. We also determined 17 candidate factors, which are likely included in the cocktail.
Highlights
Peripheral nerve injury is frequently caused by various traumatic injuries such as penetrations, crushes, tractions, and lacerations, following various sports events and road accidents [1,2]
Various cell sources have been used for nerve regeneration, such as Schwann cells and/or Schwann-like cells induced from cultivated bone marrow stromal cells [5], olfactory ensheathing cells [6], adipose tissue-derived cells [7], and skeletal muscle-derived multipotent stem cells (Sk-MSCs) [8]
When comparing the tetanic tension output of plantar flexors, the CT group showed significantly higher values than the non-cytokine control (NT) group, whereas the value of the contralateral side was similar. This suggests that more recruitment of motor units occurred in plantar flexor muscles in the CT group according to the upstream nerve reinnervation/re-connection
Summary
Peripheral nerve injury is frequently caused by various traumatic injuries such as penetrations, crushes, tractions, and lacerations, following various sports events and road accidents [1,2]. In human Sk-MSC transplantation experiments, it has been suggested that the average total/final numerical/functional recovery (75–100%) over 12 weeks may include an approximately 60–80% contribution of the paracrine effects [11] This result demonstrates the possibility that the paracrine effects of Sk-MSCs may be used as a nerve regeneration acceleration agent. Med. 2021, 10, 824 the length of the gap was adjusted to 6 mm (0.5 mm on both sides was suture marginal) At this time, a 2 mm long GFP nerve graft was stitched in the central portion of the tube (Figure 1A,B). LtoonIgM, DdiMamcoentetarin1.i0ngm2m0%, Rweinlde‐rtvype,eNadIuPlRt Om,oOusseaskear,uJmap(aAnM),Sa),nadndthceullteunrgetdhfoorf2t4heh.gTahpe was adjusted to 6 mm (0.5 mm on both sides was suture marginal) The surgical wound was sutured, a transparent sterile/analgesic plastic dressing (Nobecutan spray; Yoshitomi Chemical, Japan) was sprayed over the wound, and penicillin (4000 units/100 mL) was subcutaneously administered to prevent infection
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
