ABSTRACT
This study was performed to evaluate the effectiveness of mesenchymal stem cells (MSCs) on bone healing and to assess the role of various chemical stimulants and mediators in healing. Forty female mice were randomly assigned to 4 groups (10 mice each) after the induction of fixed fractures: group I: received fixation only; group II: received phosphate-buffered saline (PBS); group III: received intralesion MSCs (IL-MSCs); and group IV: received intraperitoneal MSCs (IP-MSCs). Serum alkaline phosphatase (ALP) levels and the expression of the osteocalcin (OCN), bone morphogenetic protein-2 (BMP-2), and stromal-derived factor-1 (SDF-1) genes were measured. ALP reached baseline level only in IL-MSCs, whereas OCN reached baseline level in MSCs recipients (IL-MSCs and IP-MSCs). BMP-2 significantly increased in MSCs recipients 3 weeks postfracture and increased in all groups 8 weeks postfracture with significant increases in MSC recipients than the fixation and PBS groups. The highest BMP-2 expression was reached in IL-MSC group. MSCs either locally or systemically improves or accelerates the healing of bone fractures with better results obtained after local injection, as shown by biochemical, radiological, and histological findings. MSCs are effective candidates for bone regeneration.
Subject(s)
Bone Marrow Cells/cytology , Fracture Healing/physiology , Fractures, Bone/physiopathology , Mesenchymal Stem Cells/cytology , Alkaline Phosphatase/metabolism , Animals , Bone Marrow Cells/metabolism , Bone Morphogenetic Protein 2/metabolism , Bone and Bones/metabolism , Bone and Bones/physiopathology , Cell Differentiation/physiology , Cells, Cultured , Chemokine CXCL12/metabolism , Female , Fractures, Bone/metabolism , Mesenchymal Stem Cells/metabolism , Mice , Mice, Inbred BALB C , Osteocalcin/metabolism , Osteocalcin/physiologyABSTRACT
Recently, studies suggested that the mesenchymal stem cells (MSCs) have anti-inflammatory and immune-modulatory roles in the induced acute lung injury in mice via controlling innate, humoral, and cell-mediated immunity. Sixty adult male mice were divided equally into three groups. Group A (control group) received an intraperitoneal (IP) phosphate-buffered saline. Group B was injected IP with lipopolysaccharide (LPS). Group C was injected IP with LPS, followed after 2 h by intravenous labeled bone marrow-derived MSCs (BM-MSCs). The plasma and bronchioalveolar lavage (BAL) fluid were collected at 12, 24, and 72 h postinjection. Estimation of total cell and neutrophils count and immunoglobulin M (IgM) in BAL fluid was performed. Enzyme-linked immunosorbent assay (ELISA) was used to analyze tumor necrosis factor-α (TNF-α) that is a proinflammatory cytokine and interleukin-10 (IL-10), which is an anti-inflammatory cytokine, in plasma. Lung samples were collected for histopathological examination at 12, 24, 72 h, and 1 week postinjection. Decreased TNF-α and increased IL-10 levels in the plasma of MSC-treated group compared to the LPS-infected group were observed. Also, decreased IgM level in BAL fluid of the MSC-treated group after 72 h compared to the LPS-infected group was detected with a resolution of inflammation and improvement in lung injury. Moreover, MSC-treated group showed a reduction in total leukocyte count and neutrophil percentage in comparison to control and LPS-infected groups. Histopathological improvement was detected in MSC-treated group as well. In conclusion, systemic MSCs injection has an anti-inflammatory and immune-modulatory effect in LPS-induced acute lung injury in mice.
