(MPCs) are a very peculiar population of cells present in the human adult bone marrow, only recently discovered and characterized. particular interest in the case of multipotent progenitors as MPCs that, retaining both mesengenic and angiogenic potential, possess a high clinical appeal. (MSCs) have been the object of extensive research for decades, due to their intrinsic clinical value. (MPCs), instead, were only Taladegib recently discovered and characterized. They were firstly co-isolated, in different percentages, with MSCs in human adult bone marrow cultures applying autologous serum (Petrini et al., 2009); later, the establishment of specific culture conditions selective for MPCs allowed IFI16 the isolation of these cells with a high grade of purity (>95%). Specifically, when human bone marrow mononuclear cells (hBM-MNCs) are cultured in basal medium supplemented with human serum (HS) on hydrophobic surfaces, it is possible to select slow-cycling MPCs after 6 days of culture (Trombi et al., 2009) because this was the only cell population present in the initial preparation capable of attaching on hydrophobic plastic dishes. Phenotypically, MPCs are easily distinguishable from MSCs for their fried egg-shape morphology and peculiar immuophenotype characterized by the positivity to CD18, CD31 and nestin as well as negativity to the MSC markers as CD73 and CD90. Interestingly, as MPCs initially showed to retain mesengenic, cardiomyogenic, and angiogenic potential, these cells were firstly named progenitor cells (Montali et al., 2016) in spite of (Pacini et al., 2016). This cell population has been sorted from adult human bone marrow as CD45lowCD31brightCD64brightCD14neg and showed similarities to monocytoid progenitors. Moreover, MPC morphology and phenotype partially resemble macrophages suggesting that these mesangiogenic progenitors and their counterparts (in order to predict the MPC differentiation fate resulting from different physico-chemical stimulations that selectively mimic specific aspects of the micro-environments. Bone tissue homeostasis represents a complex biological process finely regulated by humoral stimuli as hormones, growth factors and cytokines as well as by cell-cell and cell-matrix contact interactions (Florencio-Silva et al., 2015). Thus, optimal bone regenerative therapy should enhance mineralized tissue healing through enrichment of the bone defect with a micro/nanostructured matrix scaffold to support the wound, with cells that will give raise to osteoprogenitors and proper biochemical stimuli. Recently, a factor controlling the fate of many osteocompentent cells has been Taladegib introduced, taking in consideration that micro- e nano-topography of the bone architectures could have a role in the regulation of the activity of the bone cells trough the activation of cellular mechanotransduction mechanisms mediated by adhesion molecules (Green et al., 1995; Zohar, 2012). In particular, this complex bone architecture resulted mainly sustained by collagen and hydroxyapatite (HA), which together form a highly aligned composite matrix that contribute to the toughness and strength of bone itself (Weiner et al., 1999; Kerschnitzki et al., 2011). Collagen triple helices are typically around 300 nm long and 1.5 nm in diameter (Weiner et al., 1999) conferring Taladegib a linear topography to the bone structure at the nanoscale. Many studies reported the influence of nanotopography to the biology of osteoprogenitors (Dalby et al., 2007; McMurray et al., 2011; Janson Taladegib et al., 2014) suggesting to control their differentiation applying nanostructured surfaces of orthopedic implants. MPCs showed particular adhesion properties sustained by podosome-like structures, that were applied for the definition of a MPC selective culture method (Trombi et al., 2009). Further studies demonstrated that gelsolin-served F-actin podosomial structures were re-organizedn in paxillin-served F-actin stress fibers, during the mesengenic differentiation of MPCs (Pacini et al., 2013), suggesting that.