Alfredo Gorio

University of Milan | UNIMI · Faculty of Medicine

In this review, we describe a new avenue that involves the therapeutic use of human adipose tissue. In the past two decades, thousands of papers have described the potential clinical use of human fat and adipose tissue. Moreover, mesenchymal stem cells have been a source of great enthusiasm in clinical studies, and these have generated curiosity at...

In recent years, Autologous Fat Grafting (AFG) and related therapies using Adipose-derived stem cells (ADSCs) have garnered increasing attention for their potential in regenerating tissue. However, the available literature exhibits substantial variation, making it difficult to determine whether AFG is superior to conventional wound care or other tr...

Understanding the molecular basis of adipogenesis is vital to identify new therapeutic targets to improve anti-obesity drugs. The adipogenic process could be a new target in the management of this disease. Our aim was to evaluate the effect of GMG-43AC, a selective peroxisome proliferator-activated receptor γ (PPARγ) modulator, during adipose diffe...

Mesenchymal stem cells (MSCs) are multipotent cells able to differentiate into multiple cell types, including adipocytes, osteoblasts, and chondrocytes. The role of adipose-derived stem cells (ADSCs) in cancers is significantly relevant. They seem to be involved in the promotion of tumour development and progression and relapse processes. For this...

Spinal cord injury (SCI) is a devastating disease, which leads to paralysis and is associated to substantially high costs for the individual and society. At present, no effective therapies are available. Here, the use of mechanically-activated lipoaspirate adipose tissue (MALS) in a murine experimental model of SCI is presented. Our results show th...

The adipose tissue is a source of inflammatory proteins, such as TNF, IL-6, and CXCL8. Most of their production occurs in macrophages that act as scavengers of dying adipocytes. The application of an orbital mechanical force for 6-10 min at 97 g to the adipose tissue, lipoaspirated and treated according to Coleman procedures, abolishes the expressi...

Background Spinal cord injury (SCI) is a debilitating condition characterized by a complex of neurological dysfunctions ranging from loss of sensation to partial or complete limb paralysis. Recently, we reported that intravenous administration of neural precursors physiologically releasing erythropoietin (namely Er-NPCs) enhances functional recover...

The complex architecture of adult brain derives from tightly regulated migration and differentiation of precursor cells generated during embryonic neurogenesis. Changes at transcriptional level of genes that regulate migration and differentiation may lead to neurodevelopmental disorders. Androgen receptor (AR) is a transcription factor that is alre...

AR consensus sites in the genomic context of Sox2 upstream region. White box, Sox2 gene; gray boxes, region tested by ChIP with ChIP-grade antibodies; vertical red lines, AR consensus sites (ARE). The direction of Sox2 gene transcription is shown with arrow. The phylogenetic conservation (CNS) Mouse-human of ARSO-Sox2OTsequence is shown below the g...

Supplementary material

Aims: Hyperoxic breathing might lead to redox imbalance and signaling changes that affect cerebral function. Paradoxically, hypoxic breathing is also believed to cause oxidative stress. Our aim is to dissect the cerebral tissue responses to altered O2 fractions in breathed air by assessing the redox imbalance and the recruitment of the hypoxia sig...

Erythropoietin-releasing neural precursor cells (Er-NPCs) are a subclass of subventricular zone-derived neural progenitors, capable of surviving for 6 hr after death of donor. They present higher neural differentiation. Here, Er-NPCs were studied in animal model of Parkinson’s disease. Dopaminergic degeneration was caused by 1-methyl-4-phenyl-1,2,3...

The advent of therapies for lymphangioleiomyiomatosis (LAM) has made early diagnosis important in women with tuberous sclerosis complex (TSC), although the lifelong cumulative radiation exposure caused by CT imaging screening should not be underestimated. In 200 TSC outpatients of San Paolo Hospital (Milan, Italy) we retrospectively investigated 1)...

The advent of pharmacological therapies for lymphangioleiomyomatosis (LAM) has made early diagnosis important in women with tuberous sclerosis complex (TSC), although the lifelong cumulative radiation exposure caused by chest computer tomography (CT) should not be underestimated. We retrospectively investigated, in a cohort of TSC outpatients of Sa...

Epithelial-to-mesenchymal transition (EMT) is a core process underlying cell movement during embryonic development and morphogenesis. Cancer cells hijack this developmental program to execute a multi-step cascade, leading to tumorigenesis and metastasis. CD133 (PROM1), a marker of cancer stem cells, has been shown to facilitate EMTin various cancer...

Pulmonary lymphangioleiomyomatosis (LAM) is a rare lung disease caused by mutations in the tumor suppressor genes encoding Tuberous Sclerosis Complex (TSC) 1 and TSC2. The protein product of the TSC2 gene is a well-known suppressor of the mTOR pathway. Emerging evidence suggests that the pituitary hormone prolactin (Prl) has both endocrine and para...

Since 2005, SOX2 has raised the attention of the scientific community for being one of the key transcription factors responsible for pluripotency induction in somatic stem cells. Our research investigated the turnover regulation of SOX2 mRNA in human adipose-derived stem cells, considered one of the most valuable sources of somatic stem cells in re...

Although effective and safe, carotid endarterectomy (CEA) implies a reduced blood flow to the brain and likely an ischemia/reperfusion event. The high rate of uneventful outcomes associated with CEA suggests the activation of brain endogenous protection mechanisms aimed at limiting the possible ischemia/reperfusion damage. This study aims at assess...

Tuberous Sclerosis Complex (TSC) is characterized by the presence of benign tumors in the brain, kidneys, heart, eyes, lungs, and skin. The typical brain lesions are cortical tubers, subependimal nodules and subependymal giant-cell astrocytomas. The occurrence of malignant astrocytomas such as glioblastoma is rare. We report on a child with a clini...

The only available treatment of traumatic spinal cord injury (TSCI) is high-dose methylprednisolone (MP) administered acutely after injury. However, as the efficacy of MP is controversial, we assessed the superiority of erythropoietin (EPO) versus MP in improving clinical outcome of acute TSCI. Patients aged 18 to 65 years after C5-T12 injury, and...

Background: Among all the possible sources of mesenchymal stem cells, adipose tissue has raised great interest and has become one of the most investigated sources. Several protocols are available for isolating adipose-derived stromal cells (ASCs) and, recently, the International Fat Applied Technology Society (IFATS) highlighted the importance of s...

EGFR belongs to the HER/ErbB family of tyrosine kinase receptors and its activation in cancer cells has been linked with increased proliferation, angiogenesis, and metastasis. Lymphangioleiomyomatosis (LAM) is a rare, low-grade neoplasm that occurs sporadically or in association with tuberous sclerosis complex (TSC), a genetic, multisystem disorder...

Spinal cord injury is a devastating clinical condition, characterized by a complex of neurological dysfunctions. Animal models of spinal cord injury can be used both to investigate the biological responses to injury and to test potential therapies. Contusion or compression injury delivered to the surgically exposed spinal cord are the most widely u...

Spinal cord injury (SCI) is a debilitating clinical condition, characterized by a complex of neurological dysfunctions. Neural stem cells from the subventricular zone of the forebrain have been considered a potential tool for cell replacement therapies. We isolated recently a subclass of neural progenitors from the cadaver of mouse donors. These ce...

Spinal cord injury (SCI) is a debilitating clinical condition, characterized by a complex of neurological dysfunctions. Adult neural stem cells (NSCs) from the subventricular zone of the forebrain have been considered a potential tool for cell replacement therapies. We have recently isolated a subclass of neural progenitors from the cadaver of mous...

Spinal cord injury (SCI) is a debilitating clinical condition, characterized by a complex of neurological dysfunctions. Adult neural stem cells (NSCs) from the subventricular zone of the forebrain have been considered a potential tool for cell replacement therapies. We have recently isolated a subclass of neural progenitors from the cadaver of mous...

Background. We recently isolated a subclass of neural progenitors, capable of surviving a powerful ischemia insult: these cells were named Post Mortem Neural Precursor Cells (PM-NPCs). Differentiation yield mostly neurons (about 30-40%) compared to regular NPCs. Also the cholinergic yield is higher. PM-NPCs but not classical NPCs synthesize EPO and...

Background. Parkinson?s disease is the second most common neurodegenerative disease. The transplantation of stem cells has emerged as a promising approach to replace lost neurons in order to restore dopamine levels in the striatum. Post Mortem Neural Precursor Cells (PM-NPCs) are a subclass of SVZ-derived neural progenitors, capable of surviving ho...

Rat dermis is a source of cells capable of growing in vitro and, in appropriate conditions, forming floating spheres constituted by nestin-positive cells. We have clonally grown these spheres up to the 15th generation. These spheres can be dissociated into cells that differentiate in vitro under appropriate conditions, these cells are labeled by an...

BACKGROUND: Several types of cell-mediated treatments have been studied in order to establish their potential usefulness in promoting neural tissue regeneration and repair after spinal cord injury (SCI). We recently isolated a subclass of mouse neural progenitors, capable of surviving a powerful ischemia insult, and their differentiation yield most...

The subcutaneous adipose tissue provides a clear advantage over other mesenchymal stem cells sources due to the ease with which it can be accessed as well as to the ease of isolating the residing stem cells. Human adipose derived stem cells (hADSCs) localize in the stromal-vascular portion and can be ex vivo isolated using a combination of washing...

Lymphangioleiomyomatosis (LAM) is a rare lung disease affecting almost exclusively women, characterized by the invasion and abnormal proliferation of smooth muscle-like cells in pulmonary parenchyma and axial lymphatics. LAM cells bear mutations in Tuberous Sclerosis Complex (TSC) genes. It has been hypothesized that uterus might be the primary sit...

Figure S1 Densitometric analysis of protein levels of phospho-S6, S6, phospho-Erk, Erk was evaluated by western blotting (Fig. 3B) following incubation with rapamycin and EGFR Ab3 for 6 days 3 hrs after plating. Densitometric analysis was evaluated relatively to β-actin levels. Error bars represent the SD for four independent experiments. *P < 0.05...

Figure S3 (A) Levels of phospho-FAK, phospho-Akt, phospho-mTOR (Ser 2448), phospho-mTOR (Ser2481) and phospho-S6 (representative experiments) were evaluated by western blotting in TSC2−/meth, TSC2−/− ASM cells and in HASMCs after incubation with PF573228 (PF228; 1 or 10 μM). β-actin was evaluated as loading control. (B) Relative intensity by densit...

Figure S2 Densitometric analysis of protein levels of phospho-FAK, phospho-Akt, phospho-mTOR (Ser 2448), phospho-mTOR (Ser2481) and phospho-S6 was evaluated by western blotting (Fig. 4G) in A and NA LAM/TSC cells and after incubation with PF228 (1 or 10 μM). Densitometric analysis was measured relatively to β-actin levels. Error bars represent the...

Tuberous sclerosis complex (TSC) is caused by mutations in TSC1 or TSC2 genes. Lymphangioleiomyomatosis (LAM) can be sporadic or associated with TSC and is characterized by widespread pulmonary proliferation of abnormal α-smooth muscle (ASM)-like cells. We investigated the features of ASM cells isolated from chylous thorax of a patient affected by...

Spinal cord injury presents a significant therapeutic challenge since the treatments available are mostly vain. The use of stem cells to treat this condition represents a promising new therapeutic strategy; therefore, a variety of stem cells treatments have been recently examined in animal models of CNS trauma. In this work, we analyzed the effects...

We have previously observed changes in the RNA editing of AMPA receptors after acute spinal cord injury (SCI); this implies that post-transcriptional modifications are capable of affecting the physiological properties of glutamate receptor channels and related signal transduction in this neurodegenerative condition. Here, we report that the editing...

There have been considerable interests in attempting to reverse the deficit due to a spinal cord injury by restoring neural pathways through the lesion and by rebuilding tissue network. In order to provide an appropriate micro-environment for regrowing axotomized neurons and proliferating and migrating cells, we have implanted small block of pHPMA...

Tuberous sclerosis complex (TSC) is a multi-systemic syndrome caused by mutations in TSC1 or TSC2 gene. In TSC2-null cells Rheb, a member of the Ras family of GTPases, is constitutively activated. Statins inhibit HMG-CoA reductase and block the synthesis of isoprenoid lipids with inhibition of Rheb farnesylation and RhoA geranylgeranylation. The ef...

Hair follicle (HF) regression is characterized by the activation of apoptosis in HF cells. Dermal papilla cells play a leading role in the regulation of HF development and cycling. Human follicular dermal papilla cells (HFDPC) were used to investigate the protective activities of rutin, sperimidine and zeaxanthine. HFDP cell incubation with stauros...

Lymphangioleiomyomatosis (LAM) is an interstitial lung disease characterized by invasion and proliferation of abnormal smooth muscle (ASM) cells in lung parenchyma and axial lymphatics. LAM cells bear mutations in tuberous sclerosis (TSC) genes. TSC2(-/-) ASM cells, derived from a human renal angiomyolipoma, require epidermal growth factor (EGF) fo...

Spinal cord injury (SCI) is a debilitating clinical condition, characterized by a complex of neurological dysfunctions. It has been shown in rats that the acute administration of recombinant human erythropoietin (rhEPO) following a contusive SCI improves the recovery of hindlimb motor function, as measured with the locomotor BBB (Basso, Beattie, Br...

A novel type of adult neural precursor cells (NPCs) has been isolated from the subventricular zone of the mouse 6 hr after animal death (T6-NPCs). This condition is supposed to select hypoxia-resistant cells of scientific and clinical interest. Ionic channels are ultimately the expression of the functional maturation of neurons, so the aim of this...

Our aim was the search for new sources of cells potentially useful for central nervous system regenerative medicine. Extra-embryonic tissues are promising sources of pluripotent stem cells. Among these, human second-trimester amniotic fluid (AF) contains cell populations exhibiting self-renewal capacity, multipotency and the expression of embryonic...

Purpose: Our aim was the search for new sources of cells potentially useful for central nervous system regenerative medicine. Extra-embryonic tissues are promising sources of pluripotent stem cells. Among these, human second-trimester amniotic fluid (AF) contains cell populations exhibiting self-renewal capacity, multipotency and the expression of...

Phenotype plasticity of mesenchymal stem cells from human adipose-derived LipostemTM tissue

Erythropoietin (EPO), originally identified for its critical function in regulating production and survival of erythrocytes, is a member of the type 1 cytokine superfamily. Recent studies have shown that EPO has cytoprotective effects in a wide variety of cells and tissues. Here is presented the analysis of EPO effects on spinal cord injury (SCI),...

The purpose of this study was to determine the fate and the effects of undifferentiated embryonic stem cells (ESCs) in mice after contusive lesion of the spinal cord (SCI). Reproducible traumatic lesion to the cord was performed at T8 level by means of the Infinite Horizon Device, and was followed by intravenous injection of one million of undiffer...

Spinal cord injury (SCI) triggers a complex ischemic and inflammatory reaction, involving activation of neurotransmitter systems, in particular glutamate, culminating in cell death. We hypothesized that SCI might lead to alteration in the RNA editing of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors that govern critical deter...

The cells comprising pulmonary lymphangioleiomyomatosis (LAM) and renal angiomyolipomas (AMLs) are heterogeneous, with variable mixtures of cells exhibiting differentiation towards smooth muscle, fat, and vessels. Cells grown from LAM and AMLs have likewise tended to be heterogeneous. The discovery that LAM and AMLs contain cells with mutations in...

Spinal cord injury (SCI) is one of the most frustrating maladies faced in neurology and medicine. The vast majority of traumatic SCI patients are young, and most survivors of significant injury face the prospect of limited recovery and permanent disability. The incidence of new SCI is high, and in Italy it has been increasing dramatically recently....

Tuberous sclerosis complex (TSC) is an autosomal-dominant disease that is caused by mutations in either the TSC1 or TSC2 gene. Smooth muscle-like cells (ASMs) were isolated from an angiomyolipoma of a patient with TSC. These cells lacked tuberin, were labeled by both HMB45 and CD44v6 antibodies, and had constitutive S6 phosphorylation. The cells be...

Spinal cord injury (SCI) is a devastating event which causes dramatic changes in the everyday life of the patient. We have found that acute SCI reduced BDNF expression selectively in the hippocampus of lesioned rats, a decrease which persists at least 1 week, thus identifying the modulation of the neurotrophin biosynthesis as an important mechanism...

Effect of rapamycin (rapa) on TSC2−/−ASM cell growth. Rapamycin addition at the concentrations of 5 ng/ml 3 hours after plating did not have any significant effect on cell growth while 10, and 20 ng/ml slowed TSC2−/−ASM proliferation only after 7 days of incubation. Mean values±SEM. Significant differences (*P<0.05) versus control were evaluated by...

Densitometric analysis of phosphorylation of Akt in TSC2−/−ASM cells in complete medium or following 24 hours starvation. Incubation of TSC2−/−ASM cells and following TSC2-transfection for 2 hours with IGF-I (50 ng/ml) induced Akt phosphorylation. Incubation with PI3K inhibitor, LY294002 (LY; 20 µM), or ERK inhibitor, PD98059 (PD; 30 µM), did not i...

The aim of the study was the assessment of the effects of adult neural stem cell (NSC) transplantation in a mouse model of spinal cord injury (SCI). The contusion injury was performed by means of the Infinite Horizon Device to allow the generation of reproducible traumatic lesion to the cord. We administered green fluorescent-labeled (GFP-)NSCs eit...

Polymeric materials based on epsilon-caprolactone (CL), 1,5-dioxepan-2-one (DXO), and trimethylene carbonate (TMC) were prepared and evaluated as possible candidates for polymer-on-multielectrode (PoM) applications. CL was copolymerized with either DXO or TMC in the presence of the diol initiator 1,4-benzenedimethanol (BDM). The ring-opening polyme...

Tuberous sclerosis complex (TSC), a tumor syndrome caused by mutations in TSC1 or TSC2 genes, is characterized by the development of hamartomas. We previously isolated, from an angiomyolipoma of a TSC2 patient, a homogenous population of smooth muscle-like cells (TSC2(-/-) ASM cells) that have a mutation in the TSC2 gene as well as TSC2 loss of het...

Using a standardized rat model of contusive spinal cord injury (SCI; [Gorio A, Gokmen N, Erbayraktar S, Yilmaz O, Madaschi L, Cichetti C, Di Giulio AM, Vardar E, Cerami A, Brines M (2002) Recombinant human erythropoietin counteracts secondary injury and markedly enhances neurological recovery from experimental spinal cord trauma. Proc Natl Acad Sci...