Extracorporeal shock wave promotes growth and differentiation of bone-marrow stromal cells towards osteoprogenitors associated with induction of TGF-β1

Abstract

Extracorporeal shock-wave (ESW) treatment has been shown to be effective in promoting the healing of fractures. We aimed to determine whether ESW could enhance the growth of bone-marrow osteoprogenitor cells. We applied ESW to the left femur of rats 10 mm above the knee at 0.16 mJ/mm2 in a range of between 250 and 2000 impulses. Bone-marrow cells were harvested after ESW for one day and subjected to assessment of colony-forming unit (CFU) granulocytes, monocytes, erythocytes, megakaryocytes (CFU-Mix), CFU-stromal cells (CFU-S) and CFU-osteoprogenitors (CFU-O). We found that the mean value for the CFU-O colonies after treatment with 500 impulses of ESW was 168.2 CFU-O/well (SEM 11.3) compared with 88.2 CFU-O/well (SEM 7.2) in the control group. By contrast, ESW treatment did not affect haematopoiesis as shown by the CFU-Mix (p = 0.557). Treatment with 250 and 500 impulses promoted CFU-O, but not CFU-Mix formations whereas treatment with more than 750 impulses had an inhibiting effect. Treatment with 500 impulses also enhanced the activity of bone alkaline phosphatase in the subculture of CFU-O (p<0.01), indicating a selective promotion of growth of osteoprogenitor cells. Similarly, formation of bone nodules in the long-term culture of bone-marrow osteoprogenitor cells was also significantly enhanced by ESW treatment with 500 impulses. The mean production of TGF-beta1 was 610 pg/ml (SEM 84.6) in culture supernatants from ESW-treated rats compared with 283 pg/ml (SEM 36.8) in the control group. Our findings suggest that optimal treatment with ESW could enhance rat bone-marrow stromal growth and differentiation towards osteoprogenitors presumably by induction of TGF-beta1.

Effect of Extracorporeal Shock Wave Therapy on Cultured Tenocytes

“…Treatment with 500 shocks proved to be within the safe range in the energy intensity of 0.17mJ/mm 2 ( Figure 4A). 19,20 Further, we found that pathologic expression of MMPs 1 and 13 and IL-6 was decreased in diseased cells with shock wave treatment.…”

Effects of shock wave therapy in the skin of patients with progressive systemic sclerosis: a pilot study

“…It has been recently demonstrated that, in addition to angiogenesis due to migration and proliferation of endothelial cells in situ, EPCs contribute to neovascularization in ischemic tissue through a vasculogenetic mechanism and through secretion of a variety of angiogenic factors [18][19]. Finally, recent studies have marked out that ESW are able to recruit stem cells and to stimulate their differentiation in various damaged tissues inducing reparative phenomena [20][21][22].…”

Microvascular Response to Shock Wave Application in Striated Skin Muscle

“…The successful treatment of bony non-union when using ESWA was thought to be related to CP by causing microfractures and stimulating healing [5]. However, molecular biological investigations in rat femurs exposed to ESW demonstrated the stimulation of bone-marrow stromal growth and its differentiation towards osteoprogenitors through the induction of tumor growth factor (TGF-b1) [6]. Similar findings in a segmental bone defect model indicated a predominant chemotactic and…”