Tumor Stroma Manipulation By MSC.

Tumor stroma (TS) plays relevant roles in all steps of cancer development. We here address several fundamental aspects related with the interaction between cancer cells and their stromal counterparts. Dissecting these players is of pivotal importance to understand oncogenesis, immunoescape and drug resistance.

A novel anti-GD2/4-1BB chimeric antigen receptor triggers neuroblastoma cell killing.

Chimeric antigen receptor (CAR)-expressing T cells are a promising therapeutic option for patients with cancer. We developed a new CAR directed against the disialoganglioside GD2, a surface molecule expressed in neuroblastoma and in other neuroectoderm-derived neoplasms. The anti-GD2 single-chain variable fragment (scFv) derived from a murine antibody of IgM class was linked, via a human CD8α hinge-transmembrane domain, to the signaling domains of the costimulatory molecules 4-1BB (CD137) and CD3-ζ.

Mesenchymal stem/stromal cells as a delivery platform in cell and gene therapies.

Regenerative medicine relying on cell and gene therapies is one of the most promising approaches to repair tissues. Multipotent mesenchymal stem/stromal cells (MSC), a population of progenitors committing into mesoderm lineages, are progressively demonstrating therapeutic capabilities far beyond their differentiation capacities. The mechanisms by which MSC exert these actions include the release of biomolecules with anti-inflammatory, immunomodulating, anti-fibrogenic, and trophic functions.

In vitro differentiation of human amniotic epithelial cells into insulin-producing 3D spheroids.

Regenerative medicine and stem cell therapy may represent the solution for the treatment of non-curable human diseases such as type 1 diabetes. In this context of growing demand for functional and safe stem cells, human amniotic epithelial cells (hAECs) from term placenta have attracted increasing interest for their wide availability, stem cell properties, and differentiation plasticity, which make them a promising tool for stem cell-based therapeutic applications. We initially assayed the stemness characteristics of hAECs in serum-free conditions.

Mesenchymal progenitors aging highlights a miR-196 switch targeting HOXB7 as master regulator of proliferation and osteogenesis.

Human aging is associated with a decrease in tissue functions combined with a decline in stem cells frequency and activity followed by a loss of regenerative capacity. The molecular mechanisms behind this senescence remain largely obscure, precluding targeted approaches to counteract aging. Focusing on mesenchymal stromal/stem cells (MSC) as known adult progenitors, we identified a specific switch in miRNA expression during aging, revealing a miR-196a upregulation which was inversely correlated with MSC proliferation through HOXB7 targeting.

Mesenchymal progenitors expressing TRAIL induce apoptosis in sarcomas.

Sarcomas are frequent tumors in children and young adults that, despite a relative chemo-sensitivity, show high relapse rates with up to 80% of metastatic patients dying in 5 years from diagnosis. The real ontogeny of sarcomas is still debated and evidences suggest they may derive from precursors identified within mesenchymal stromal/stem cells (MSC) fractions. Recent studies on sarcoma microenvironment additionally indicated that MSC could take active part in generation of a supportive stroma.

Paraplegia by spinal cord compression as the initial manifestation of Hodgkin's disease: a case report.

The 90% of Hodgkin's disease (HD) cases are originated by lymphnodes whereas 10% by extranodal regions as epidural space. Neurologic complications of HD can be classified as directly resulting from the disease or indirectly originated from the disease or from its treatment. Patients very rarely present with spinal cord compression (SCC)  due to epidural HD.

Final height and body mass index in adult survivors of childhood acute lymphoblastic leukemia treated without cranial radiotherapy: a retrospective longitudinal multicenter Italian study.

Background: Young adult survivors of childhood acute lymphoblastic leukemia (ALL) treated with protocols including cranial radiotherapy demonstrate a persistent weight gain and reduced final height. Published reports on the effects on growth of different oncologic therapies are conflicting and difficult to interpret because they combined children treated with both cranial irradiation and multi-agent chemotherapy. Our study investigated the effect of chemotherapy alone on body mass index (BMI) and on growth at the achievement of final height in a homogeneous cohort of Italian childhood ALL survivors.

cGMP-compliant transportation conditions for a prompt therapeutic use of marrow mesenchymal stromal/stem cells.

We recently described conditions for safe 18-h manufacturer-to-patient transportation of freshly harvested hBM-MSC expanded under cGMP protocols using human platelet lysate (hPL), that allowed prompt use as an advanced therapeutic medicinal product. Here we outline important considerations when comparing different transportation conditions, highlighting that although cell transportation may involve a reduction in viability, this did not undermine the ultimate bone-forming regenerative potential of the cGMP-hBM-MSC population.

Size and dispersion of urticating setae in three species of processionary moths.

Larvae of the processionary moths of the Palaearctic region bear urticating setae that are released against vertebrate predators, especially insectivorous birds. A few species are pests of forest and urban trees and, consequently, may threaten human and animal health during outbreaks, causing dermatitis, conjunctivitis and respiratory distress. Although some studies provide detailed information about the setae, particularly those of the pine processionary moth Thaumetopoea pityocampa, there is little knowledge on the morphological traits of the setae and their release by the larvae.

Sickle cell disease in areas of immigration of high-risk populations: a low cost and reproducible method of screening in northern Italy.

Background: From 2005 to 2010, we observed a 10-fold increase of newly diagnosed sickle cell disease in children in the province of Modena (northern Italy). The median age at diagnosis was 24 months. Since these children are too old for optimal disease management, earlier detection of the disease is needed for prophylaxis and comprehensive care before the occurrence of clinical manifestations.

Predictive diagnostic value for the clinical features accompanying intellectual disability in children with pathogenic copy number variations: a multivariate analysis.

Background: Array comparative genomic hybridization (a-CGH) has become the first-tier investigation in patients with unexplained developmental delay/intellectual disability (DD/ID). Although the costs are progressively decreasing, a-CGH is still an expensive and labour-intensive technique: for this reason a definition of the categories of patients that can benefit the most of the analysis is needed. Aim of the study was to retrospectively analyze the clinical features of children with DD/ID attending the outpatient clinic of the Mother & Child Department of the University Hospital of Modena subjected to a-CGH, to verify by uni- and multivariate analysis the independent predictors of pathogenic CNVs.

Dancing eye syndrome as first symptom of neuroblastoma.

Background: "Dancing eye syndrome", also called Kinsbourne syndrome or Opsoclonus-Myoclonus-Ataxia Syndrome (OMS) is a rare neurological disorder that in children is frequently associated to occult, low-grade neuroblastoma (NB) (>50% of the cases). OMS may also be triggered by infections and it is often associated to developmental impairment and disability.

Case Presentation: We discuss the case of a 16 months old female with acutely onset of OMS associated to occult stage III NB.

Delayed marrow infusion in mice enhances hematopoietic and osteopoietic engraftment by facilitating transient expansion of the osteoblastic niche.

Transplantation of bone marrow cells leads to engraftment of osteopoietic and hematopoietic progenitors. We sought to determine whether the recently described transient expansion of the host osteoblastic niche after marrow radioablation promotes engraftment of both osteopoietic and hematopoietic progenitor cells. Mice infused with marrow cells 24 hours after total body irradiation (TBI) demonstrated significantly greater osteopoietic and hematopoietic progenitor chimerism than did mice infused at 30 minutes or 6 hours.

Transportation conditions for prompt use of ex vivo expanded and freshly harvested clinical-grade bone marrow mesenchymal stromal/stem cells for bone regeneration.

Successful preliminary studies have encouraged a more translational phase for stem cell research. Nevertheless, advances in the culture of human bone marrow-derived mesenchymal stromal/stem cells (hBM-MSC) and osteoconductive qualities of combined biomaterials can be undermined if necessary cell transportation procedures prove unviable. We aimed at evaluating the effect of transportation conditions on cell function, including the ability to form bone in vivo, using procedures suited to clinical application.

Adipose stromal/stem cells assist fat transplantation reducing necrosis and increasing graft performance.

Autologous fat transfer (AFT) is a procedure for adipose tissue (AT) repair after trauma, burns, post-tumor resections and lipodystrophies still negatively impacted by the lack of graft persistence. The reasons behind this poor outcome are unclear and seem to involve damages in either harvested/transplanted mature adipocytes or on their mesenchymal progenitors, namely adipose stromal/stem cells (ASC), and due to post-transplant AT apoptosis and involution. A rabbit subcutaneous AT regeneration model was here developed to first evaluate graft quality at different times after implant focusing on related parameters, such as necrosis and vasculogenesis.

IGF-1-mediated osteoblastic niche expansion enhances long-term hematopoietic stem cell engraftment after murine bone marrow transplantation.

The efficiency of hematopoietic stem cell (HSC) engraftment after bone marrow (BM) transplantation depends largely on the capacity of the marrow microenvironment to accept the transplanted cells. While radioablation of BM damages osteoblastic stem cell niches, little is known about their restoration and mechanisms governing their receptivity to engraft transplanted HSCs. We previously reported rapid restoration and profound expansion of the marrow endosteal microenvironment in response to marrow radioablation.

Intellectual function evaluation of first generation immigrant children with sickle cell disease: the role of language and sociodemographic factors.

Background: Sickle Cell Disease (SCD) is the most common genetic disease worldwide. Neurological events are among the most worrisome clinical complications of SCD and are frequently accompanied by cognitive impairment. Intellectual function in SCD may vary according to genetic and environmental factors.

Megakaryocytes promote murine osteoblastic HSC niche expansion and stem cell engraftment after radioablative conditioning.

Successful hematopoietic stem cell (HSC) transplantation requires donor HSC engraftment within specialized bone marrow microenvironments known as HSC niches. We have previously reported a profound remodeling of the endosteal osteoblastic HSC niche after total body irradiation (TBI), defined as relocalization of surviving megakaryocytes to the niche site and marked expansion of endosteal osteoblasts. We now demonstrate that host megakaryocytes function critically in expansion of the endosteal niche after preparative radioablation and in the engraftment of donor HSC.

Isolation, characterization, and transduction of endometrial decidual tissue multipotent mesenchymal stromal/stem cells from menstrual blood.

Mesenchymal stromal/stem cells (MSCs) reveal progenitor cells-like features including proliferation and differentiation capacities. One of the most historically recognized sources of MSC has been the bone marrow, while other sources recently include adipose tissue, teeth, bone, muscle, placenta, liver, pancreas, umbilical cord, and cord blood. Frequently, progenitor isolation requires traumatic procedures that are poorly feasible and associated with patient discomfort.

Unusual osseous presentation of blastomycosis in an immigrant child: a challenge for European pediatricians.

Background: Blastomycosis, caused by the thermally dimorphic fungus Blastomyces dermatitidis is a systemic pyogranulomatous infection, endemic in United States and Canada, with few reported cases in Africa and Asia. It is uncommon among children and adolescents, ranging from 3% to 10%. Clinical features vary from asymptomatic spontaneously healing pneumonia, through acute or chronic pneumonia, to a malignant appearing lung mass.

MSC and Tumors: Homing, Differentiation, and Secretion Influence Therapeutic Potential.

: Mesenchymal stromal/stem cells (MSC) are adult multipotent progenitors with fibroblast-like morphology able to differentiate into adipocytic, osteogenic, chondrogenic, and myogenic lineages. Due to these properties, MSC have been studied and introduced as therapeutics in regenerative medicine. Preliminary studies have also shown a possible involvement of MSC as precursors of cellular elements within tumor microenvironments, in particular tumor-associated fibroblasts (TAF).

Incidental diagnosis of thoracic ganglioneuroblastoma in a 3-year-old female with wheezing.

Ganglioneuroblastoma (GNB) is a cancer of the peripheral sympathetic nervous system and represents the 30% of cases of Neuroblastoma. When originates from thoracic ganglia it may appear very late, with severe symptoms like respiratory distress or neurological dysfunctions. We present an incidental diagnosis of thoracic GNB, discovered by a chest radiography during a recurrent wheezing unresponsive to bronchodilators.

Leukemia risk in children exposed to benzene and PM10 from vehicular traffic: a case-control study in an Italian population.

Benzene, a recognized occupational leukemogen in adults, has been hypothesized to also increase the risk of childhood leukemia. We carried out a population-based case-control study in a northern Italy community involving 83 cases with acute childhood leukemia diagnosed in the years 1998-2009 and 332 matched controls. We assessed residential exposure to benzene and to particulate matter ≤10 μm (PM10) from motorized traffic using geocoded residences and detailed emission and dispersion modeling.

Epidemiology of infections in children with acquired aplastic anaemia: a retrospective multicenter study in Italy.

Infection is a significant cause of death in patients with aplastic anaemia (AA). However, few studies have examined the characteristics of infections in patients with AA, especially in children. The aim of this retrospective study was to evaluate the incidence and types of infections in a large cohort of paediatric patients with AA referred to eight AIEOP (Italian Association of Paediatric Oncology and Haematology) centres in Italy.