wanda lattanzi - Academia.edu (original) (raw)

Papers by wanda lattanzi

Research paper thumbnail of Quali-quantitative differences of adipose tissuederived stromal cells from superficial and deep subcutaneous lipoaspirates: a matter of fat

Subcutaneous fat (or hypoderm) represents a valuable reservoir of adiposederived stem cells (ASCs... more Subcutaneous fat (or hypoderm) represents a valuable reservoir of adiposederived stem cells (ASCs), residing in the stromal vascular fraction (SVF), widely exploited in regenerative medicine applications, being easily harvested through lipoaspiration. The lack for standardized procedures for autologous fat grafting, guided research efforts aimed at identifying possible differences related to the harvesting site, that may affect cell isolation yield, cell growth properties and clinical outcomes. The hypoderm features a complex architecture: the superficial fascia separates the superficial adipose tissue (SAT) from the deep layer (DAT). Aim of this study was to unravel the differences between SAT and DAT, considering morphological structure, SVF composition and ASCs’ properties. SAT and DAT specimens were collected from three distinct anatomical regions (abdomen, thigh and knee) of female individuals and comparatively analyzed through histology, flow citometry, and qPCR. ASCs were iso...

Research paper thumbnail of BMP2 or not BMP2? A SMAD6-related question in craniosynostosis

European Journal of Human Genetics, 2019

Research paper thumbnail of Cloning of the Minimal Functional Domainof Human Lim Mineralization Protein-3 Able ToInduce Bone Mineralization: In Vitro and In VivoStudy

Research paper thumbnail of Schizophrenia and human self-domestication: a linguistic approach

Schizophrenia (SZ) is a pervasive neurodevelopmental disorder entailing social and cognitive defi... more Schizophrenia (SZ) is a pervasive neurodevelopmental disorder entailing social and cognitive deficits, including marked problems with language. SZ incidence has always been high and quite stable in human populations, across time and regardless of cultural implications, due to unclear reasons. Also, its complex multifactorial aetiopathogenesis, including genetic and environmental factors, is widely uncertain. It has been hypothesised that SZ pathophysiology may involve the biological components that changed during the recent human evolutionary history and led to our distinctive mode of cognition, which includes language skills. In this paper we explore this possibility, focusing on the self-domestication of the human species. This has been claimed to account for many human-specific distinctive traits, including aspects of our linguistic abilities. The “domestication syndrome” in mammals comprises the constellation of traits exhibited by domesticated strains, seemingly resulting from ...

Research paper thumbnail of Shaping modern human skull through epigenetic, transcriptional and post-transcriptional regulation of the RUNX2 master bone gene

Scientific Reports

RUNX2 encodes the master bone transcription factor driving skeletal development in vertebrates, a... more RUNX2 encodes the master bone transcription factor driving skeletal development in vertebrates, and playing a specific role in craniofacial and skull morphogenesis. The anatomically modern human (AMH) features sequence changes in the RUNX2 locus compared with archaic hominins’ species. We aimed to understand how these changes may have contributed to human skull globularization occurred in recent evolution. We compared in silico AMH and archaic hominins’ genomes, and used mesenchymal stromal cells isolated from skull sutures of craniosynostosis patients for in vitro functional assays. We detected 459 and 470 nucleotide changes in noncoding regions of the AMH RUNX2 locus, compared with the Neandertal and Denisovan genomes, respectively. Three nucleotide changes in the proximal promoter were predicted to alter the binding of the zinc finger protein Znf263 and long-distance interactions with other cis-regulatory regions. By surface plasmon resonance, we selected nucleotide substitutions...

Research paper thumbnail of Personalized Bone Reconstruction and Regeneration in the Treatment of Craniosynostosis

Applied Sciences

Craniosynostosis (CS) is the second most prevalent craniofacial congenital malformation due to th... more Craniosynostosis (CS) is the second most prevalent craniofacial congenital malformation due to the premature fusion of skull sutures. CS care requires surgical treatment of variable complexity, aimed at resolving functional and cosmetic defects resulting from the skull growth constrain. Despite significant innovation in the management of CS, morbidity and mortality still exist. Residual cranial defects represent a potential complication and needdedicated management to drive a targeted bone regeneration while modulating suture ossification. To this aim, existing techniques are rapidly evolving and include the implementation of novel biomaterials, 3D printing and additive manufacturing techniques, and advanced therapies based on tissue engineering. This review aims at providing an exhaustive and up-to-date overview of the strategies in use to correct these congenital defects, focusing on the technological advances in the fields of biomaterials and tissue engineering implemented in ped...

Research paper thumbnail of Basic and Preclinical Research for Personalized Medicine

Journal of Personalized Medicine

Basic and preclinical research founded the progress of personalized medicine by providing a prodi... more Basic and preclinical research founded the progress of personalized medicine by providing a prodigious amount of integrated profiling data and by enabling the development of biomedical applications to be implemented in patient-centered care and cures. If the rapid development of genomics research boosted the birth of personalized medicine, further development in omics technologies has more recently improved our understanding of the functional genome and its relevance in profiling patients’ phenotypes and disorders. Concurrently, the rapid biotechnological advancement in diverse research areas enabled uncovering disease mechanisms and prompted the design of innovative biological treatments tailored to individual patient genotypes and phenotypes. Research in stem cells enabled clarifying their role in tissue degeneration and disease pathogenesis while providing novel tools toward the development of personalized regenerative medicine strategies. Meanwhile, the evolving field of integra...

Research paper thumbnail of Challenges and Innovations in Osteochondral Regeneration: Insights from Biology and Inputs from Bioengineering toward the Optimization of Tissue Engineering Strategies

Journal of Functional Biomaterials

Due to the extremely high incidence of lesions and diseases in aging population, it is critical t... more Due to the extremely high incidence of lesions and diseases in aging population, it is critical to put all efforts into developing a successful implant for osteochondral tissue regeneration. Many of the patients undergoing surgery present osteochondral fissure extending until the subchondral bone (corresponding to a IV grade according to the conventional radiographic classification by Berndt and Harty). Therefore, strategies for functional tissue regeneration should also aim at healing the subchondral bone and joint interface, besides hyaline cartilage. With the ambition of contributing to solving this problem, several research groups have been working intensively on the development of tailored implants that could promote that complex osteochondral regeneration. These implants may be manufactured through a wide variety of processes and use a wide variety of (bio)materials. This review aimed to examine the state of the art regarding the challenges, advantages, and drawbacks of the cu...

Research paper thumbnail of Graphene Quantum Dots’ Surface Chemistry Modulates the Sensitivity of Glioblastoma Cells to Chemotherapeutics

International Journal of Molecular Sciences

Recent evidence has shown that graphene quantum dots (GQDs) are capable of crossing the blood–bra... more Recent evidence has shown that graphene quantum dots (GQDs) are capable of crossing the blood–brain barrier, the barrier that reduces cancer therapy efficacy. Here, we tested three alternative GQDs’ surface chemistries on two neural lineages (glioblastoma cells and mouse cortical neurons). We showed that surface chemistry modulates GQDs’ biocompatibility. When used in combination with the chemotherapeutic drug doxorubicin, GDQs exerted a synergistic effect on tumor cells, but not on neurons. This appears to be mediated by the modification of membrane permeability induced by the surface of GQDs. Our findings highlight that GQDs can be adopted as a suitable delivery and therapeutic strategy for the treatment of glioblastoma, by both directly destabilizing the cell membrane and indirectly increasing the efficacy of chemotherapeutic drugs.

Research paper thumbnail of GLI1 and AXIN2 Are Distinctive Markers of Human Calvarial Mesenchymal Stromal Cells in Nonsyndromic Craniosynostosis

International Journal of Molecular Sciences

All skeletal bones house osteogenic stem cell niches, in which mesenchymal stromal cells (MSC) pr... more All skeletal bones house osteogenic stem cell niches, in which mesenchymal stromal cells (MSC) provide progenitors for tissue growth and regeneration. They have been widely studied in long bones formed through endochondral ossification. Limited information is available on the composition of the osteogenic niche in flat bones (i.e., skull vault bones) that develop through direct membranous ossification. Craniosynostosis (CS) is a congenital craniofacial defect due to the excessive and premature ossification of skull vault sutures. This study aimed at analysing the expression of GLI1, AXIN2 and THY1 in the context of the human skull vault, using nonsyndromic forms of CS (NCS) as a model to test their functional implication in the aberrant osteogenic process. The expression of selected markers was studied in NCS patients’ calvarial bone specimens, to assess the in vivo location of cells, and in MSC isolated thereof. The marker expression profile was analysed during in vitro osteogenic ...

Research paper thumbnail of Correction: SMAD6 variants in craniosynostosis: genotype and phenotype evaluation

Genetics in Medicine

An amendment to this paper has been published and can be accessed via a link at the top of the pa... more An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Research paper thumbnail of Rising Roles of Small Noncoding RNAs in Cotranscriptional Regulation: In Silico Study of miRNA and piRNA Regulatory Network in Humans

Genes

Gene expression regulation is achieved through an intricate network of molecular interactions, in... more Gene expression regulation is achieved through an intricate network of molecular interactions, in which trans-acting transcription factors (TFs) and small noncoding RNAs (sncRNAs), including microRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs), play a key role. Recent observations allowed postulating an interplay between TFs and sncRNAs, in that they may possibly share DNA-binding sites. The aim of this study was to analyze the complete subset of miRNA and piRNA sequences stored in the main databases in order to identify the occurrence of conserved motifs and subsequently predict a possible innovative interplay with TFs at a transcriptional level. To this aim, we adopted an original in silico workflow to search motifs and predict interactions within genome-scale regulatory networks. Our results allowed categorizing miRNA and piRNA motifs, with corresponding TFs sharing complementary DNA-binding motifs. The biological interpretation of the gene ontologies of the TFs permitted observ...

Research paper thumbnail of Collagen Scaffold and Lipoaspirate Fluid-derived Stem Cells for the Treatment of Cartilage Defects in a Rabbit Model

Revista de Chimie

The purpose of the present study was to assess and compare the chondroregenerative properties of ... more The purpose of the present study was to assess and compare the chondroregenerative properties of PLA (processed lipoaspirate) and LAF (lipoaspirate fluid) cells, in a preclinical rabbit model of knee cartilage defect. The defects were repaired by a collagen I/III scaffold and added LAF-cells, PLA-cells or no cells, upon the study group. The results showed that collagen scaffolds seeded with LAF-derived stem cells appear to have slightly better activity and outcomes when compared to PLA-cells, in terms of cartilage regeneration.

Research paper thumbnail of Graphene Oxide Induced Osteogenesis Quantification by In-Situ 2D-Fluorescence Spectroscopy

International Journal of Molecular Sciences

Graphene and graphene oxide can promote the adhesion, growth and differentiation of mesenchymal s... more Graphene and graphene oxide can promote the adhesion, growth and differentiation of mesenchymal stem cells. Further, graphene surface coatings accelerate the differentiation of human mesenchymal stem cells acting as osteogenic inducers. Quantification of the osteogenic induction is conventionally performed with Alizarin Red S (ARS), an anthraquinone derivative used to identify calcium deposits in tissue sections and cell cultures. The ARS staining is quite versatile because the dye forms an Alizarin Red S–calcium complex that can be extracted from the stained monolayer of cells and readily assayed by absorbance measurements. Direct visualization of stained deposits is also feasible; however, an in-situ visualization and quantification of deposits is possible only on transparent supports and not on thick opaque materials like ceramics and graphene composites that are well-known inducers of osteogenesis. In this manuscript, the shape of the 2D-fluorescence spectra of the ARS-calcium c...

Research paper thumbnail of Liposuction Aspirate Fluid Adipose-Derived Stem Cell Injection and Secondary Healing in Fingertip Injury

Plastic and Reconstructive Surgery

www.PRSJournal.com 1400 Liposuction Aspirate Fluid Adipose-Derived Stem Cell Injection and Second... more www.PRSJournal.com 1400 Liposuction Aspirate Fluid Adipose-Derived Stem Cell Injection and Secondary Healing in Fingertip Injury: A Pilot Study: Correction T authors of the July 2018 Hand/Peripheral Nerve article entitled “Liposuction Aspirate Fluid Adipose-Derived Stem Cell Injection and Secondary Healing in Fingertip Injury: A Pilot Study” (Plast Reconstr Surg. 2018;142:136–147), wish to make the following corrections:

Research paper thumbnail of BBS9 gene in nonsyndromic craniosynostosis: Role of the primary cilium in the aberrant ossification of the suture osteogenic niche

Bone, 2018

Nonsyndromic craniosynostosis (NCS) is the premature ossification of skull sutures, without assoc... more Nonsyndromic craniosynostosis (NCS) is the premature ossification of skull sutures, without associated clinical features. Mutations in several genes account for a small number of NCS patients; thus, the molecular etiopathogenesis of NCS remains largely unclear. Our study aimed at characterizing the molecular signaling implicated in the aberrant ossification of sutures in NCS patients. Comparative gene expression profiling of NCS patient sutures identified a fused suture-specific signature, including 17 genes involved in primary cilium signaling and assembly. Cells from fused sutures displayed a reduced potential to form primary cilia compared to cells from control patent sutures of the same patient. We identified specific upregulated splice variants of the Bardet Biedl syndrome-associated gene 9 (BBS9), which encodes a structural component of the ciliary BBSome complex. BBS9 expression increased during in vitro osteogenic differentiation of suture-derived mesenchymal cells of NCS pa...

Research paper thumbnail of Skeletal Muscle MicroRNAs as Key Players in the Pathogenesis of Amyotrophic Lateral Sclerosis

International journal of molecular sciences, Jan 22, 2018

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder, for which, to date, no... more Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder, for which, to date, no effective treatment to ameliorate the clinical manifestations is available. The long-standing view of ALS as affecting only motor neurons has been challenged by the finding that the skeletal muscle plays an active role in the disease pathogenesis and can be a valuable target for therapeutic strategies. In recent years, non-coding RNAs, including microRNAs, have emerged as important molecules that play key roles in several cellular mechanisms involved in the pathogenic mechanisms underlying various human conditions. In this review, we summarize how the expression of some microRNAs is dysregulated in the skeletal muscle of ALS mouse models and patients. Shedding light on the mechanisms underlying microRNAs dysregulation in the skeletal muscle could clarify some of the processes involved in the pathogenesis of ALS and especially identify new promising therapeutic targets in patients.

Research paper thumbnail of A craniosynostosis massively parallel sequencing panel study in 309 Australian and New Zealand patients: findings and recommendations

Genetics in medicine : official journal of the American College of Medical Genetics, Sep 7, 2017

PurposeThe craniosynostoses are characterized by premature fusion of one or more cranial sutures.... more PurposeThe craniosynostoses are characterized by premature fusion of one or more cranial sutures. The relative contribution of previously reported genes to craniosynostosis in large cohorts is unclear. Here we report on the use of a massively parallel sequencing panel in individuals with craniosynostosis without a prior molecular diagnosis.MethodsA 20-gene panel was designed based on the genes' association with craniosynostosis, and clinically validated through retrospective testing of an Australian and New Zealand cohort of 233 individuals with craniosynostosis in whom previous testing had not identified a causative variant within FGFR1-3 hot-spot regions or the TWIST1 gene. An additional 76 individuals were tested prospectively.ResultsPathogenic or likely pathogenic variants in non-FGFR genes were identified in 43 individuals, with diagnostic yields of 14% and 15% in retrospective and prospective cohorts, respectively. Variants were identified most frequently in TCF12 (N = 22)...

Research paper thumbnail of Four-Dimensional Bioprinting As a New Era for Tissue Engineering and Regenerative Medicine

Frontiers in bioengineering and biotechnology, 2017

Research paper thumbnail of Adipose-derived stem cell therapies for bone regeneration

Expert Opinion on Biological Therapy

Introduction: Cell-based therapies exploit the heterogeneous and self-sufficient biological envir... more Introduction: Cell-based therapies exploit the heterogeneous and self-sufficient biological environment of stem cells to restore, maintain and improve tissue functions. Adipose-derived stem cells (ASCs) are, to this aim, promising cell types thanks to advantageous isolation procedures, growth kinetics, plasticity and trophic properties. Specifically, bone regeneration represents a suitable, though often challenging, target setting to test and apply ASC-based therapeutic strategies. Areas covered: ASCs are extremely plastic and secrete bioactive peptides that mediate paracrine functions, mediating their trophic actions in vivo. Numerous preclinical studies demonstrated that ASCs improve bone healing. Clinical trials are ongoing to validate the clinical feasibility of these approaches. This review is intended to define the state-of-the-art on ASCs, encompassing the biological features that make them suitable for bone regenerative strategies, and to provide an update on existing preclinical and clinical applications. Expert opinion: ASCs offer numerous advantages over other stem cells in terms of feasibility of clinical translation. Data obtained from in vivo experimentation are encouraging, and clinical trials are ongoing. More robust validations are thus expected to be achieved during the next few years, and will likely pave the way to optimized patient-tailored treatments for bone regeneration.

Research paper thumbnail of Quali-quantitative differences of adipose tissuederived stromal cells from superficial and deep subcutaneous lipoaspirates: a matter of fat

Subcutaneous fat (or hypoderm) represents a valuable reservoir of adiposederived stem cells (ASCs... more Subcutaneous fat (or hypoderm) represents a valuable reservoir of adiposederived stem cells (ASCs), residing in the stromal vascular fraction (SVF), widely exploited in regenerative medicine applications, being easily harvested through lipoaspiration. The lack for standardized procedures for autologous fat grafting, guided research efforts aimed at identifying possible differences related to the harvesting site, that may affect cell isolation yield, cell growth properties and clinical outcomes. The hypoderm features a complex architecture: the superficial fascia separates the superficial adipose tissue (SAT) from the deep layer (DAT). Aim of this study was to unravel the differences between SAT and DAT, considering morphological structure, SVF composition and ASCs’ properties. SAT and DAT specimens were collected from three distinct anatomical regions (abdomen, thigh and knee) of female individuals and comparatively analyzed through histology, flow citometry, and qPCR. ASCs were iso...

Research paper thumbnail of BMP2 or not BMP2? A SMAD6-related question in craniosynostosis

European Journal of Human Genetics, 2019

Research paper thumbnail of Cloning of the Minimal Functional Domainof Human Lim Mineralization Protein-3 Able ToInduce Bone Mineralization: In Vitro and In VivoStudy

Research paper thumbnail of Schizophrenia and human self-domestication: a linguistic approach

Schizophrenia (SZ) is a pervasive neurodevelopmental disorder entailing social and cognitive defi... more Schizophrenia (SZ) is a pervasive neurodevelopmental disorder entailing social and cognitive deficits, including marked problems with language. SZ incidence has always been high and quite stable in human populations, across time and regardless of cultural implications, due to unclear reasons. Also, its complex multifactorial aetiopathogenesis, including genetic and environmental factors, is widely uncertain. It has been hypothesised that SZ pathophysiology may involve the biological components that changed during the recent human evolutionary history and led to our distinctive mode of cognition, which includes language skills. In this paper we explore this possibility, focusing on the self-domestication of the human species. This has been claimed to account for many human-specific distinctive traits, including aspects of our linguistic abilities. The “domestication syndrome” in mammals comprises the constellation of traits exhibited by domesticated strains, seemingly resulting from ...

Research paper thumbnail of Shaping modern human skull through epigenetic, transcriptional and post-transcriptional regulation of the RUNX2 master bone gene

Scientific Reports

RUNX2 encodes the master bone transcription factor driving skeletal development in vertebrates, a... more RUNX2 encodes the master bone transcription factor driving skeletal development in vertebrates, and playing a specific role in craniofacial and skull morphogenesis. The anatomically modern human (AMH) features sequence changes in the RUNX2 locus compared with archaic hominins’ species. We aimed to understand how these changes may have contributed to human skull globularization occurred in recent evolution. We compared in silico AMH and archaic hominins’ genomes, and used mesenchymal stromal cells isolated from skull sutures of craniosynostosis patients for in vitro functional assays. We detected 459 and 470 nucleotide changes in noncoding regions of the AMH RUNX2 locus, compared with the Neandertal and Denisovan genomes, respectively. Three nucleotide changes in the proximal promoter were predicted to alter the binding of the zinc finger protein Znf263 and long-distance interactions with other cis-regulatory regions. By surface plasmon resonance, we selected nucleotide substitutions...

Research paper thumbnail of Personalized Bone Reconstruction and Regeneration in the Treatment of Craniosynostosis

Applied Sciences

Craniosynostosis (CS) is the second most prevalent craniofacial congenital malformation due to th... more Craniosynostosis (CS) is the second most prevalent craniofacial congenital malformation due to the premature fusion of skull sutures. CS care requires surgical treatment of variable complexity, aimed at resolving functional and cosmetic defects resulting from the skull growth constrain. Despite significant innovation in the management of CS, morbidity and mortality still exist. Residual cranial defects represent a potential complication and needdedicated management to drive a targeted bone regeneration while modulating suture ossification. To this aim, existing techniques are rapidly evolving and include the implementation of novel biomaterials, 3D printing and additive manufacturing techniques, and advanced therapies based on tissue engineering. This review aims at providing an exhaustive and up-to-date overview of the strategies in use to correct these congenital defects, focusing on the technological advances in the fields of biomaterials and tissue engineering implemented in ped...

Research paper thumbnail of Basic and Preclinical Research for Personalized Medicine

Journal of Personalized Medicine

Basic and preclinical research founded the progress of personalized medicine by providing a prodi... more Basic and preclinical research founded the progress of personalized medicine by providing a prodigious amount of integrated profiling data and by enabling the development of biomedical applications to be implemented in patient-centered care and cures. If the rapid development of genomics research boosted the birth of personalized medicine, further development in omics technologies has more recently improved our understanding of the functional genome and its relevance in profiling patients’ phenotypes and disorders. Concurrently, the rapid biotechnological advancement in diverse research areas enabled uncovering disease mechanisms and prompted the design of innovative biological treatments tailored to individual patient genotypes and phenotypes. Research in stem cells enabled clarifying their role in tissue degeneration and disease pathogenesis while providing novel tools toward the development of personalized regenerative medicine strategies. Meanwhile, the evolving field of integra...

Research paper thumbnail of Challenges and Innovations in Osteochondral Regeneration: Insights from Biology and Inputs from Bioengineering toward the Optimization of Tissue Engineering Strategies

Journal of Functional Biomaterials

Due to the extremely high incidence of lesions and diseases in aging population, it is critical t... more Due to the extremely high incidence of lesions and diseases in aging population, it is critical to put all efforts into developing a successful implant for osteochondral tissue regeneration. Many of the patients undergoing surgery present osteochondral fissure extending until the subchondral bone (corresponding to a IV grade according to the conventional radiographic classification by Berndt and Harty). Therefore, strategies for functional tissue regeneration should also aim at healing the subchondral bone and joint interface, besides hyaline cartilage. With the ambition of contributing to solving this problem, several research groups have been working intensively on the development of tailored implants that could promote that complex osteochondral regeneration. These implants may be manufactured through a wide variety of processes and use a wide variety of (bio)materials. This review aimed to examine the state of the art regarding the challenges, advantages, and drawbacks of the cu...

Research paper thumbnail of Graphene Quantum Dots’ Surface Chemistry Modulates the Sensitivity of Glioblastoma Cells to Chemotherapeutics

International Journal of Molecular Sciences

Recent evidence has shown that graphene quantum dots (GQDs) are capable of crossing the blood–bra... more Recent evidence has shown that graphene quantum dots (GQDs) are capable of crossing the blood–brain barrier, the barrier that reduces cancer therapy efficacy. Here, we tested three alternative GQDs’ surface chemistries on two neural lineages (glioblastoma cells and mouse cortical neurons). We showed that surface chemistry modulates GQDs’ biocompatibility. When used in combination with the chemotherapeutic drug doxorubicin, GDQs exerted a synergistic effect on tumor cells, but not on neurons. This appears to be mediated by the modification of membrane permeability induced by the surface of GQDs. Our findings highlight that GQDs can be adopted as a suitable delivery and therapeutic strategy for the treatment of glioblastoma, by both directly destabilizing the cell membrane and indirectly increasing the efficacy of chemotherapeutic drugs.

Research paper thumbnail of GLI1 and AXIN2 Are Distinctive Markers of Human Calvarial Mesenchymal Stromal Cells in Nonsyndromic Craniosynostosis

International Journal of Molecular Sciences

All skeletal bones house osteogenic stem cell niches, in which mesenchymal stromal cells (MSC) pr... more All skeletal bones house osteogenic stem cell niches, in which mesenchymal stromal cells (MSC) provide progenitors for tissue growth and regeneration. They have been widely studied in long bones formed through endochondral ossification. Limited information is available on the composition of the osteogenic niche in flat bones (i.e., skull vault bones) that develop through direct membranous ossification. Craniosynostosis (CS) is a congenital craniofacial defect due to the excessive and premature ossification of skull vault sutures. This study aimed at analysing the expression of GLI1, AXIN2 and THY1 in the context of the human skull vault, using nonsyndromic forms of CS (NCS) as a model to test their functional implication in the aberrant osteogenic process. The expression of selected markers was studied in NCS patients’ calvarial bone specimens, to assess the in vivo location of cells, and in MSC isolated thereof. The marker expression profile was analysed during in vitro osteogenic ...

Research paper thumbnail of Correction: SMAD6 variants in craniosynostosis: genotype and phenotype evaluation

Genetics in Medicine

An amendment to this paper has been published and can be accessed via a link at the top of the pa... more An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Research paper thumbnail of Rising Roles of Small Noncoding RNAs in Cotranscriptional Regulation: In Silico Study of miRNA and piRNA Regulatory Network in Humans

Genes

Gene expression regulation is achieved through an intricate network of molecular interactions, in... more Gene expression regulation is achieved through an intricate network of molecular interactions, in which trans-acting transcription factors (TFs) and small noncoding RNAs (sncRNAs), including microRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs), play a key role. Recent observations allowed postulating an interplay between TFs and sncRNAs, in that they may possibly share DNA-binding sites. The aim of this study was to analyze the complete subset of miRNA and piRNA sequences stored in the main databases in order to identify the occurrence of conserved motifs and subsequently predict a possible innovative interplay with TFs at a transcriptional level. To this aim, we adopted an original in silico workflow to search motifs and predict interactions within genome-scale regulatory networks. Our results allowed categorizing miRNA and piRNA motifs, with corresponding TFs sharing complementary DNA-binding motifs. The biological interpretation of the gene ontologies of the TFs permitted observ...

Research paper thumbnail of Collagen Scaffold and Lipoaspirate Fluid-derived Stem Cells for the Treatment of Cartilage Defects in a Rabbit Model

Revista de Chimie

The purpose of the present study was to assess and compare the chondroregenerative properties of ... more The purpose of the present study was to assess and compare the chondroregenerative properties of PLA (processed lipoaspirate) and LAF (lipoaspirate fluid) cells, in a preclinical rabbit model of knee cartilage defect. The defects were repaired by a collagen I/III scaffold and added LAF-cells, PLA-cells or no cells, upon the study group. The results showed that collagen scaffolds seeded with LAF-derived stem cells appear to have slightly better activity and outcomes when compared to PLA-cells, in terms of cartilage regeneration.

Research paper thumbnail of Graphene Oxide Induced Osteogenesis Quantification by In-Situ 2D-Fluorescence Spectroscopy

International Journal of Molecular Sciences

Graphene and graphene oxide can promote the adhesion, growth and differentiation of mesenchymal s... more Graphene and graphene oxide can promote the adhesion, growth and differentiation of mesenchymal stem cells. Further, graphene surface coatings accelerate the differentiation of human mesenchymal stem cells acting as osteogenic inducers. Quantification of the osteogenic induction is conventionally performed with Alizarin Red S (ARS), an anthraquinone derivative used to identify calcium deposits in tissue sections and cell cultures. The ARS staining is quite versatile because the dye forms an Alizarin Red S–calcium complex that can be extracted from the stained monolayer of cells and readily assayed by absorbance measurements. Direct visualization of stained deposits is also feasible; however, an in-situ visualization and quantification of deposits is possible only on transparent supports and not on thick opaque materials like ceramics and graphene composites that are well-known inducers of osteogenesis. In this manuscript, the shape of the 2D-fluorescence spectra of the ARS-calcium c...

Research paper thumbnail of Liposuction Aspirate Fluid Adipose-Derived Stem Cell Injection and Secondary Healing in Fingertip Injury

Plastic and Reconstructive Surgery

www.PRSJournal.com 1400 Liposuction Aspirate Fluid Adipose-Derived Stem Cell Injection and Second... more www.PRSJournal.com 1400 Liposuction Aspirate Fluid Adipose-Derived Stem Cell Injection and Secondary Healing in Fingertip Injury: A Pilot Study: Correction T authors of the July 2018 Hand/Peripheral Nerve article entitled “Liposuction Aspirate Fluid Adipose-Derived Stem Cell Injection and Secondary Healing in Fingertip Injury: A Pilot Study” (Plast Reconstr Surg. 2018;142:136–147), wish to make the following corrections:

Research paper thumbnail of BBS9 gene in nonsyndromic craniosynostosis: Role of the primary cilium in the aberrant ossification of the suture osteogenic niche

Bone, 2018

Nonsyndromic craniosynostosis (NCS) is the premature ossification of skull sutures, without assoc... more Nonsyndromic craniosynostosis (NCS) is the premature ossification of skull sutures, without associated clinical features. Mutations in several genes account for a small number of NCS patients; thus, the molecular etiopathogenesis of NCS remains largely unclear. Our study aimed at characterizing the molecular signaling implicated in the aberrant ossification of sutures in NCS patients. Comparative gene expression profiling of NCS patient sutures identified a fused suture-specific signature, including 17 genes involved in primary cilium signaling and assembly. Cells from fused sutures displayed a reduced potential to form primary cilia compared to cells from control patent sutures of the same patient. We identified specific upregulated splice variants of the Bardet Biedl syndrome-associated gene 9 (BBS9), which encodes a structural component of the ciliary BBSome complex. BBS9 expression increased during in vitro osteogenic differentiation of suture-derived mesenchymal cells of NCS pa...

Research paper thumbnail of Skeletal Muscle MicroRNAs as Key Players in the Pathogenesis of Amyotrophic Lateral Sclerosis

International journal of molecular sciences, Jan 22, 2018

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder, for which, to date, no... more Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder, for which, to date, no effective treatment to ameliorate the clinical manifestations is available. The long-standing view of ALS as affecting only motor neurons has been challenged by the finding that the skeletal muscle plays an active role in the disease pathogenesis and can be a valuable target for therapeutic strategies. In recent years, non-coding RNAs, including microRNAs, have emerged as important molecules that play key roles in several cellular mechanisms involved in the pathogenic mechanisms underlying various human conditions. In this review, we summarize how the expression of some microRNAs is dysregulated in the skeletal muscle of ALS mouse models and patients. Shedding light on the mechanisms underlying microRNAs dysregulation in the skeletal muscle could clarify some of the processes involved in the pathogenesis of ALS and especially identify new promising therapeutic targets in patients.

Research paper thumbnail of A craniosynostosis massively parallel sequencing panel study in 309 Australian and New Zealand patients: findings and recommendations

Genetics in medicine : official journal of the American College of Medical Genetics, Sep 7, 2017

PurposeThe craniosynostoses are characterized by premature fusion of one or more cranial sutures.... more PurposeThe craniosynostoses are characterized by premature fusion of one or more cranial sutures. The relative contribution of previously reported genes to craniosynostosis in large cohorts is unclear. Here we report on the use of a massively parallel sequencing panel in individuals with craniosynostosis without a prior molecular diagnosis.MethodsA 20-gene panel was designed based on the genes' association with craniosynostosis, and clinically validated through retrospective testing of an Australian and New Zealand cohort of 233 individuals with craniosynostosis in whom previous testing had not identified a causative variant within FGFR1-3 hot-spot regions or the TWIST1 gene. An additional 76 individuals were tested prospectively.ResultsPathogenic or likely pathogenic variants in non-FGFR genes were identified in 43 individuals, with diagnostic yields of 14% and 15% in retrospective and prospective cohorts, respectively. Variants were identified most frequently in TCF12 (N = 22)...

Research paper thumbnail of Four-Dimensional Bioprinting As a New Era for Tissue Engineering and Regenerative Medicine

Frontiers in bioengineering and biotechnology, 2017

Research paper thumbnail of Adipose-derived stem cell therapies for bone regeneration

Expert Opinion on Biological Therapy

Introduction: Cell-based therapies exploit the heterogeneous and self-sufficient biological envir... more Introduction: Cell-based therapies exploit the heterogeneous and self-sufficient biological environment of stem cells to restore, maintain and improve tissue functions. Adipose-derived stem cells (ASCs) are, to this aim, promising cell types thanks to advantageous isolation procedures, growth kinetics, plasticity and trophic properties. Specifically, bone regeneration represents a suitable, though often challenging, target setting to test and apply ASC-based therapeutic strategies. Areas covered: ASCs are extremely plastic and secrete bioactive peptides that mediate paracrine functions, mediating their trophic actions in vivo. Numerous preclinical studies demonstrated that ASCs improve bone healing. Clinical trials are ongoing to validate the clinical feasibility of these approaches. This review is intended to define the state-of-the-art on ASCs, encompassing the biological features that make them suitable for bone regenerative strategies, and to provide an update on existing preclinical and clinical applications. Expert opinion: ASCs offer numerous advantages over other stem cells in terms of feasibility of clinical translation. Data obtained from in vivo experimentation are encouraging, and clinical trials are ongoing. More robust validations are thus expected to be achieved during the next few years, and will likely pave the way to optimized patient-tailored treatments for bone regeneration.