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Regulated self-consumption, also known as autophagy, is an evolutionary conserved process that degrades cellular components by directing them to the lysosomal compartment of eukaryotic cells. As a major intracellular degradation and recycling pathway, autophagy is crucial for maintaining and remodeling cellular homeostasis during normal cellular and tissue development. Recent studies have demonstrated that autophagy is necessary for the maintenance of cellular stemness and for a number of differentiation processes, including the lineage determination of mesenchymal stem cells. These are multipotent progenitor cells with self-renewal capacities that can give rise to a subset of tissues and thus hold a consistent potential in regenerative medicine. Here, we review the current literature on the complex liaison between autophagy induced by various extra- or intracellular stimuli and the molecular targets that affect mesenchymal stem cells proliferation and differentiation. [ABSTRACT FROM AUTHOR]

Blood vessels have a fundamental role both in skeletal homeostasis and in bone repair. Angiogenesis is also important for a successful bone engineering. Therefore, scaffolds should be tested for their ability to favour endothelial cell adhesion, proliferation and functions. The type of endothelial cell to use for in vitro assays should be carefully considered, because the properties of these cells may depend on their source. Morphological and functional relationships between endothelial cells and osteoblasts are evaluated with co-cultures, but this model should still be standardized, particularly for distinguishing the two cell types. Platelet-rich plasma and recombinant growth factors may be useful for stimulating angiogenesis. [ABSTRACT FROM AUTHOR]

Autologous platelet gel, which is usually prepared by adding thrombin and calcium to a platelet concentrate, is used to accelerate bone repair as a possible alternative to recombinant growth factors (GF), through the osteogenic GF released from alpha-granules. The advantages of platelet gel lie in its mimicking the GF effects of the physiological bone healing and regenerative processes, in addition to a relatively simple and low cost technique. Moreover, if autologous platelet gel is used, immunological reactions are avoided. In in vitro systems, platelet gel stimulated osteogenic differentiation of bone marrow stromal cells, while it inhibited complete osteoclast differentiation and activation. Moreover, platelet gel favoured endothelial cell proliferation and expression of pro-osteogenic functions. In experimental animals and in clinical application, the efficacy of platelet gel was increased by the combination with bone allografts, acting as scaffolds, and with bone marrow stromal cells. [ABSTRACT FROM AUTHOR]

Freeze-dried bone allograft (FDBA) might be more effective in combination with platelet rich plasma (PRP) and bone marrow stromal cells (BMSC) in accelerating bone healing. The isolation of BMSC through density gradient (pBMSC) is not extensively applicable in clinical practice, because it increases the risk of infection. Alternatively, BMSC can be concentrated by simple centrifugation (wBMSC) directly in the operating room. However, we do not know if wBMSC act in the same way as pBMSC. BMSC from 10 donors were tested whether, in the presence of a combination of FDBA and autologous PRP, the osteogenic differentiation of the cells concentrated by simple centrifugation (wBMSC + FDBA + PRP) was similar to that of pBMSC. Cell-associated alkaline phosphatase, osterix and fibroblast growth factor-2 were higher in wBMSC + FDBA + PRP. In conclusion, the combination of FDBA and PRP had a favouring effect on the differentiation towards osteoblasts and allowed BMSC concentrated by simple centrifugation to differentiate as fast as BMSC purified by density gradient. [ABSTRACT FROM AUTHOR]

Marrow stromal cells (MSC) are increasingly being introduced in orthopaedic practice as potentially powerful effectors of bone regeneration. Since cell recovery of MSC is affected by a high degree of individual variability, sources for collecting adequate amounts of safe and effective MSC under routine conditions are needed. We analysed if femoral bone marrow, which is usually discarded during total hip arthroplasty procedures, is a reliable source of MSC to enhance bone healing and regeneration. Mononuclear cells were isolated, assayed for typical MSC markers, harvested under appropriate culture conditions and evaluated for their ability to differentiate into osteoblasts. Cell recovery and osteogenic potential were independent from donor gender or age, suggesting that elderly individuals are eligible for autologous cell therapy. Although heterogeneous, the pool of MSC recoveredfrom femoral marrow without further in vitro selection or manipulation proved highly effective in proliferating and differentiating along the osteogenic lineage. In conclusion, this source of MSC offers a valuable tool to be used to promote osteogenesis and implant fixation. [ABSTRACT FROM AUTHOR]