Accelerated functional recovery after skeletal muscle ischemia-reperfusion injury using freshly isolated bone marrow cells.
BACKGROUND
Relatively little information exists regarding the usefulness of bone marrow-derived cells for skeletal muscle ischemia-reperfusion injury (I/R), especially when compared with I/R that occurs in other tissues. The objectives of this study were to evaluate the ability of freshly isolated bone marrow cells to home to injured skeletal muscle and to determine their effects on muscle regeneration.


METHODS
Freshly isolated lineage-depleted bone marrow cells (Lin(-) BMCs) were injected intravenously 2 d after I/R. Bioluminescent imaging was used to evaluate cell localization for up to 28 d after injury. Muscle function, the percentage of fibers with centrally located nuclei, and the capillary-to-fiber ratio were evaluated 14 d after delivery of either saline (Saline) or saline containing Lin(-) BMCs (Lin(-) BMCs).


RESULTS
Bioluminescence was higher in the injured leg than the contralateral control leg for up to 7 d after injection (P < 0.05) suggestive of cell homing to the injured skeletal muscle. Fourteen days after injury, there was a significant improvement in maximal tetanic torque (40% versus 22% deficit; P < 0.05), a faster rate of force production (+dP/dt) (123.6 versus 94.5 Nmm/S; P < 0.05), and a reduction in the percentage of fibers containing centrally located nuclei (40 versus 17%; P < 0.05), but no change in the capillary-to-fiber ratio in the Lin(-) BMC as compared with the Saline group.


CONCLUSIONS
The homing of freshly isolated BMCs to injured skeletal muscle after I/R is associated with an increase in functional outcomes.
Department of Extremity Trauma and Regenerative Medicine, United States Army Institute of Surgical Research, Fort Sam Houston, Texas.
Benjamin T
BT
Corona
Department of Extremity Trauma and Regenerative Medicine, United States Army Institute of Surgical Research, Fort Sam Houston, Texas. Electronic address: christopher.r.rathbone.civ@mail.mil.
Christopher R
CR
Rathbone
D000818:Animals; D001835:Body Weight; D016026:Bone Marrow Transplantation; D005260:Female; D006614:Hindlimb / Q000098:blood supply / Q000473:pathology; D008163:Luminescent Measurements; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000473:pathology / Q000502:physiology; D012038:Regeneration; D015427:Reperfusion Injury / Q000473:pathology / Q000628:therapy*
Bone marrow; Injury; Ischemia; Reperfusion; Skeletal muscle; Stem cell