This corrects the article DOI: 10.1038/bjc.2017.85.

One of the most important issues in orthopaedic surgery is the loss of bone resulting from trauma, infections, tumours or congenital deficiency. In view of the hypothetical future application of mesenchymal stem cells isolated from human adipose tissue in regenerative medicine, we have analysed and characterized adipose-derived stem cells (ASCs) isolated from adipose tissue of rat, rabbit and pig. We have compared their in vitro osteogenic differentiation abilities for exploitation in the repair of critical osteochondral defects in autologous pre-clinical models. The number of pluripotent cells per millilitre of adipose tissue is variable and the yield of rabbit ASCs is lower than that in rat and pig. However, all ASCs populations show both a stable doubling time during culture and a marked clonogenic ability. After exposure to osteogenic stimuli, ASCs from rat, rabbit and pig exhibit a significant increase in the expression of osteogenic markers such as alkaline phosphatase, extracellular calcium deposition, osteocalcin and osteonectin. However, differences have been observed depending on the animal species and/or differentiation period. Rabbit and porcine ASCs have been differentiated on granules of clinical grade hydroxyapatite (HA) towards osteoblast-like cells. These cells grow and adhere to the scaffold, with no inhibitory effect of HA during osteo-differentiation. Such in vitro studies are necessary in order to select suitable pre-clinical models to validate the use of autologous ASCs, alone or in association with proper biomaterials, for the repair of critical bone defects.

Stem cells hold great promise in tissue engineering for repairing tissues damaged by disease or injury. Mesenchymal stem cells (MSCs) are multipotent cells able to proliferate and differentiate into multiple mesodermal tissues such as bone, cartilage, muscle, tendon, and fat. We have previously reported that the low-affi nity nerve growth factor receptor (L-NGFR or CD271) defi nes a subset of cells with high proliferative, clonogenic, and multipotential differentiation ability in adult bone marrow (BM). It has been recently shown that adipose tissue is an alternative source of adult multipotent stem cells and human adipose-derived stem cells, selected by plastic adherence (PA hASCs), have been extensively characterized for their functional potentials in vitro. In this study, immunoselected L-NGFR + and CD34 + subpopulations have been analyzed and compared with the PA hASCs. Phenotypic profi le of freshly purifi ed subpopulations showed an enrichment in the expression of some stem cell markers; indeed, a great percentage of L-NGFR + cells co-expressed CD34 and CD117 antigens, whereas the endothelial-committed progenitor markers KDR and P1H12 were mainly expressed on CD34 + cells. Differently from PA hASCs, the immunoseparated fractions showed high increments in cell proliferation, and the fi broblast colony-forming activity (CFU-F) was maintained throughout the time of culture. Furthermore, the immunoselected populations showed a greater differentiative potential toward adipocytes, osteoblasts, and chondrocytelike cells, compared to PA hASCs. Our data suggest that both CD34+ and L-NGFR + hASCs can be considered alternative candidates for tissue engineering and regenerative medicine applications. IntroductionI n the recent years, the emerging fi eld of cell-based therapies for repair and regeneration of damaged tissues has been focusing on the identifi cation of the ideal source of stem cells, which combines the ability of multipotential differentiation and the accessibility in large amounts under a minimally invasive procedure, not complicated by immunological rejection concerns and ethical controversies.Adult mesenchymal stem cells (MSCs) are a population of multipotent cells able to proliferate and differentiate into multiple mesodermal tissues. MSCs have been initially identifi ed in bone marrow (BM) [ 1 ], but have been subsequently isolated from many other tissues [ 2-10 ]. Among them, human MSCs derived from adipose tissue (hASCs) show stem cell key features such as the ability to form fi broblast-like colonies (CFU-F), the expression of several common cell surface antigens, the capacity of extensive proliferation, and the potential to differentiate in vitro and in vivo into multiple lineages of mesodermal origin, and also to transdifferentiate into neurogenic and hepatic lineages [ 4 , 11-21 ]. Similarly to BM-derived MSCs (BM MSCs), hASCs are able to suppress immunoreactivity, suggesting a possible overcoming of histocompatibility limitations in allogeneic transplantation [ 22 , 23 ]; furthermore, they ar...

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Over the last decade, it has been proved that mesenchymal stem cells (MSCs) elicit anti-inflammatory effects. MSCs from adipose tissue (hASCs) differentiate into cells of the mesodermal lineage and transdifferentiate into ectodermal-origin cells. Although there are various etiologies to chronic pain, one common feature is that painful states are associated with increased inflammation. We believe in hASCs as a therapeutic tool also in pathologies involving neuroinflammation and neuronal tissue damage. We have investigated the effect of hASCs injected in a model of neuropathic pain [(mouse sciatic nerve chronic constriction injury (CCI)]. hASCs from 5 donors were characterized, and no major differences were depicted. hASCs were cryopreserved and grown on demand. About 1×10(6), 3×10(6), and 6×10(6) hASCs were intravenously injected into normal immunocompetent mice. No mouse died, and no macroscopic toxicity or behavioral changes were observed, confirming the safety of hASCs. hASCs, intravenously (i.v.) injected into C57BL/6 mice when the neuropathic pain was already established, induced a significant reduction in mechanical allodynia and a complete reversion of thermal hyperalgesia in a dose-response fashion, already 1 day after administration. Moreover, the hASCs effect can be boosted by repeated administrations, allowing a prolonged therapeutic effect. Treatment decreased the level of the CCI-induced proinflammatory cytokine interleukin (IL)-1β and activated the anti-inflammatory cytokine IL-10 in the lesioned nerve. hASCs treatment also restored normal inducible nitric oxide synthase expression in the spinal cord of CCI animals. Our data suggest that hASCs are worthy of further studies as an anti-inflammatory therapy in the treatment of neuropathic pain or chronic inflammatory diseases.