Role of bone marrow and mesenchymal stem cells in healing after traumatic injury

Abstract

The role of bone marrow-derived cells (BMDCs) and mesenchymal stem cells (MSC) in healing of traumatic-induced injury remains poorly understood. Mesenteric lymph duct ligation (LDL) results in decreased BMDC mobilization and impaired healing. We hypothesized that LDL-mediated impaired healing would be abrogated by reinjection of BMDC or MSC. Sprague-Dawley rats were subjected to LDL + lung contusion (LC+LDL) with or without injection of BMDCs or MSCs. Unmanipulated control (UC) and lung contusion alone (LC) served as controls. BMDC and MSC homing was assessed by hematopoietic progenitor cell (HPC [granulocyte-, erythrocyte-, monocyte-, and megakaryocyte colony-forming units; erythroid burst-forming units; and erythroid colony-forming units]) colony growth and immunofluorescent microscopic tracking of tagged MSC, respectively. Histologic lung injury score (LIS) was used to grade injury. Data are mean ± SD. *P < .05/Student t test. Lung HPC growth was decreased in LC+LDL versus LC alone (HPC colonies: 2 ± 2, 4 ± 3, 4 ± 2 vs. 11 ± 2, 20 ± 6, 22 ± 9. *P < .05). LC+LDL had greater degree of lung injury on days 5 and 7 LC alone (LIS: 5 ± 1, 4 ± 1 vs. 3 ± 1, 1 ± 0.4. *P < .05). BMDC injection into rats with LC + LDL increased lung HPC growth to LC level (HPC colonies: 12 ± 2, 19 ± 5, 17 ± 4 vs 11 ± 2, 20 ± 6, 22 ± 9. P > .05). Injected MSCs into LC+LDL rats homed preferentially to contused versus noncontused lung (MSC/high-powered field: 6 ± 4 vs. 2 ± 2 *P < .05). Either BMDC or MSC injection into LC+LDL rats returned lung injury to LC level on day 7 (LIS: 1 ± 0.4 and 1 ± 1 vs. 1 ± 0.4. P > .05). LDL-mediated impaired tissue healing is abrogated by either whole BMDC or MSC injection. This highlights the critical role of BMDC and MSC on healing of trauma-induced injury.