BackgroundOrthotopic liver transplantation is the only effective treatment for liver failure but limited with shortage of available donor organs. Recent studies show promising results of mesenchymal stem cells (MSCs)-based therapies.MethodsWe systematically investigate the therapeutic effects of MSCs or MSC-conditioned medium (MSC-CM) in ameliorating fulminant hepatic failure (FHF) and chronic liver fibrosis in mice. In addition, extensive flow cytometry analysis of spleens from vehicle and MSC- and MSC-CM-treated mice was applied to reveal the alteration of inflammatory state.ResultsIn FHF model, MSCs treatment reduced remarkably the death incidents; the analysis of gross histopathology showed that control livers were soft and shrunken with extensive extravasated blood, which was gradually reduced at later time points, while MSC–treated livers showed gross pathological changes, even 24 h after MSC infusion, and hematoxylin and eosin staining revealed dramatical hepatocellular death with cytoplasmic vacuolization suppressed by MSCs treatment; flow cytometry analysis of total lymphocytes showed that macrophages (F4/80) infiltrated into control livers more than MSC-treated livers; by contrast, MSC-CM partially ameliorates FHF. In chronic liver injury model, MSC and MSC-CM both suppressed fibrogenesis and necroinflammatory, and the later was better; activation of hepatic stellate cells (α-SMA) was inhibited; glycogen synthesis and storage (indicated by periodic acid-Schiff -staining) was improved; liver regeneration (Ki67) was promoted while liver apoptosis (TUNEL) was reduced. In the in vitro, MSCs promote macrophage line RAW264.7 apoptosis and MSC-CM promotes apoptosis and inhibits proliferation of HSC line LX-2. We also found that MSCs and MSC-CM could improve spleen; MSC-CM increased levels of Th2 and Treg cells, and reduced levels of Th17 cells, whereas levels of Th1 cells were unchanged; comparatively, MSC treatment did not affect Th17 and Treg cells and only slightly alters inflammatory state; MSC and MSC-CM treatment both substantially down-regulated macrophages in the spleens.ConclusionBoth MSCs and MSC-CM exert therapeutic effects by acting on various key cells during the pathogenesis of FHF and chronic fibrosis, stimulating hepatocyte proliferation and suppressing apoptosis, down-regulating infiltrating macrophages, converting CD4+ T lymphocyte system into an anti-inflammatory state, and facilitating hepatic stellate cell death.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-0792-1) contains supplementary material, which is available to authorized users.

Reconstruction of massive bone defects is challenging for orthopaedic clinicians, especially in cases of severe trauma and resection of tumors in various locales. Autologous iliac crest bone graft (ICBG) is the “gold standard” for bone grafting. However, the limited availability and complications at donor sites resulted in seeking other options like allografts and bone graft substitutes. Demineralized bone matrix (DBM) is a form of allograft using acidic solution to remove mineral components, while leaving much of the proteinaceous components native to bone, with small amounts of calcium‐based solids, inorganic phosphates, and some trace cell debris. It is an osteoconductive and osteoinductive biomaterial and is approved as a medical device for use in bone defects and spinal fusion. To pack consistently into the defect sites and stay firmly in the filling parts, DBM products have various forms combined with biocompatible viscous carriers, including sponges, strips, injectable putty, paste, and paste infused with chips. The present review aims to summarize the properties of various kind of viscous carriers and their clinical use combined with DBM in commercially available products. Given DBM'mercially available products. Given DBM;s long clinical track record and commercial accessibility in standard forms, opportunities to further develop and validate DBM as a versatile bone biomaterial in orthopaedic repair and regenerative medicine contexts are attractive.

Background Core decompression (CD) is an important method for the treatment of osteonecrosis of the femoral head (ONFH). Few articles investigate the influence of core decompression on outcomes of ONFH. This study was carried out to observe the safety and effectiveness of core decompression in the treatment of ONFH. Methods A comprehensive literature search of databases including PubMed, Embase, and Cochrane Library was performed to collect the related studies. The medical subject headings used were “femur head necrosis” and “Core decompression.” The relevant words in title or abstract included but not limited to “Osteonecrosis of the Femoral Head,” “femoral head necrosis,” “avascular necrosis of femoral head,” and “ischemic necrosis of femoral head.” The methodological index for nonrandomized studies was adopted for assessing the studies included in this review. Results Thirty-two studies included 1865 patients (2441 hips). Twenty-one studies (1301 hips) using Ficat staging standard, 7 studies (338hips) using Association Research Circulation Osseous (ARCO) staging standard, and University of Pennsylvania system for staging avascular necrosis (UPSS) staging criteria for 4 studies (802 hips). All the studies recorded the treatment, 22 studies (1379 hips) were treated with core decompression (CD) alone, and 7 studies (565 hips) were treated with core decompression combined with autologous bone (CD Autologous bone). Nine subjects (497 hips) were treated with core decompression combined with autologous bone marrow (CD Marrow). Twenty-seven studies (2120 hips) documented the number of conversion to total hip replacement (THA), and 26 studies (1752hips) documented the number of radiographic progression (RP). Twenty-one studies recorded the types of complications and the number of cases, a total of 69 cases. The random-effect model was used for meta-analysis, and the results showed that the overall success rate was 65%. The rate of success showed significant difference on the outcomes of different stages. The rate of success, conversion to THA, and radiographic progression showed significant difference on the outcomes of ONFH using different treatments. Conclusions Core decompression is an effective and safe method of treating ONFH. The combined use of autologous bone or bone marrow can increase the success rate. For advanced femoral head necrosis, the use of CD should be cautious. High-quality randomized controlled trials and prospective studies will be necessary to clarify the effects of different etiology factors, treatments, and postoperative rehabilitation. Until then, the surgeon can choose core decompression to treat ONFH depending on the patient’s condition. Level of evidence I Meta-analysis

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