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Erythropoietin improves functional and histological recovery of traumatized skeletal muscle tissue

Apart from its hematopoietic effect, erythropoietin (EPO) is known as pleiotropic cytokine with anti‐inflammatory and anti‐apoptotic properties. Here, we evaluated for the first time the EPO‐dependent regeneration capacity in an in vivo rat model of skeletal muscle trauma. A myoblast cell line was used to study the effect of EPO on serum deprivation‐induced cell apoptosis in vitro. A crush injury was performed to the left soleus muscle in 80 rats treated with either EPO or saline. Muscle recovery was assessed by analysis of contraction capacities. Intravital microscopy, BrdU/laminin double immunohistochemistry and cleaved caspase‐3 immunohistochemistry of muscle tissue on days 1, 7, 14, and 42 posttrauma served for assessment of local microcirculation, tissue integrity, and cell proliferation. Serum deprivation‐induced myoblast apoptosis of 23.9 ± 1.5% was reduced by EPO to 17.2 ± 0.8%. Contraction force analysis in the EPO‐treated animals revealed significantly improved muscle strength with 10–20% higher values of twitch and tetanic forces over the 42‐day observation period. EPO‐treated muscle tissue displayed improved functional capillary density as well as reduced leukocytic response and consecutively macromolecular leakage over day 14. Concomitantly, muscle histology showed significantly increased numbers of BrdU‐positive satellite cells and interstitial cells as well as slightly lower counts of cleaved caspase‐3‐positive interstitial cells. EPO results in faster and better regeneration of skeletal muscle tissue after severe trauma and goes along with improved microcirculation. Thus, EPO, a compound established as clinically safe, may represent a promising therapeutic option to optimize the posttraumatic course of muscle tissue healing. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res