Effects of mesenchymal stem cells injection on muscle protein synthesis after resistance exercise in mice with type 2 diabetes mellitus

Mito Watanabe, Satoshi Fujita, Junya Takegaki, Ryo Takagi
Purpose:

The present study aimed to investigate the effect of intramuscular injection of MSCs on muscle protein synthesis and related factors after an acute bout of resistance exercise in mice with T2DM.The present study aimed to investigate the effect of intramuscular injection of MSCs on muscle protein synthesis and related factors after an acute bout of resistance exercise in mice with T2DM.

Methods:

Male db/db mice were divided into placebo and MSCs groups (10 weeks old, N = 5 and 6, respectively). All mice were intramuscularly injected with either MSCs (2.0 × 106 cells suspended in 20 μL PBS) labeled with green fluorescence protein or vehicle-only placebo into both gastrocnemius muscle under isoflurane anesthesia. Seven days after the injection, all mice performed 3s × 10 reps × 5 sets maximal isometric contraction elicited by transcutaneous electrical stimulation as resistance exercise on the right gastrocnemius muscle. Three hours after the exercise bout, gastrocnemius muscle samples were collected. Left gastrocnemius muscle in each group was kept as sedentary. All experiments were approved by the Ethics Committee for Animal Experiments at Ritsumeikan University (BKC-2023-002).

Results:

The expression of green fluorescent protein was observed in both gastrocnemius muscle in MSCs group. Muscle protein synthesis was increased in the exercised muscle in both groups (main effect of exercise, P 0.01), but that was not enhanced by injection of MSCs. Resistance exercise increased the expression of phosphorylated p70S6K (Thr389) in both groups (main effect of exercise, P 0.0001), but injection of MSCs decreased them (main effect of MSCs, P 0.05). On the other hand, resistance exercise increased the expression of phosphorylated 4EBP1 (Thr37/46) in both groups (main effect of exercise, P 0.0001), and injection of MSCs further increased them (main effect of MSCs, P 0.01). The expression of LC3-II and K48 linkage-specific polyubiquitin were not altered by resistance exercise or injection of MSCs.

Conclusion(s):

The present results suggest that intramuscular injection of MSCs does not augment activation of muscle protein synthesis after resistance exercise in mice with T2DM.

Implications:

In T2DM, stem cell transplantation into skeletal muscle is unlikely to change the effects of exercise therapy aimed at muscle hypertrophy.

Funding acknowledgements:
This study was supported by a research grant from The Nakatomi Foundation and The Ritsumeikan Global Innovation Research Organization project.
Keywords:
type 2 diabetes mellitus
resistance exercise
mesenchymal stem cells
Primary topic:
Basic science including molecular and cellular health
Second topic:
Musculoskeletal
Third topic:
Other
Did this work require ethics approval?:
Yes
Name the institution and ethics committee that approved your work:
Ethics Committee for Animal Experiments at Ritsumeikan University
Provide the ethics approval number:
BKC-2023-002
Has any of this material been/due to be published or presented at another national or international conference prior to the World Physiotherapy Congress 2025?:
No

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