Nanoparticles in tissue engineering: applications, challenges and prospects

Anwarul Hasan,1 Mahboob Morshed,2 Adnan Memic,3 Shabir Hassan,4,5 Thomas J Webster,6 Hany El-Sayed Marei7 1Department of Mechanical and Industrial Engineering, Qatar University, Doha, Qatar; 2School of Life Sciences, Independent University, Bangladesh (IUB), Dhaka, Bangladesh; 3Center of Nanotechnology, King Abdulaziz University, Jeddah, Saudi Arabia; 4Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA; 5Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA; 6Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 7Biomedical Research Center, Qatar University, Doha, Qatar Abstract: Tissue engineering (TE) is an interdisciplinary field integrating engineering, material science and medical biology that aims to develop biological substitutes to repair, replace, retain, or enhance tissue and organ-level functions. Current TE methods face obstacles including a lack of appropriate biomaterials, ineffective cell growth and a lack of techniques for capturing appropriate physiological architectures as well as unstable and insufficient production of growth factors to stimulate cell communication and proper response. In addition, the inability to control cellular functions and their various properties (biological, mechanical, electrochemical and others) and issues of biomolecular detection and biosensors, all add to the current limitations in this field. Nanoparticles are at the forefront of nanotechnology and their distinctive size-dependent properties have shown promise in overcoming many of the obstacles faced by TE today. Despite tremendous progress in the use of nanoparticles over the last 2 decades, the full potential of the applications of nanoparticles in solving TE problems has yet to be realized. This review presents an overview of the diverse applications of various types of nanoparticles in TE applications and challenges that need to be overcome for nanotechnology to reach its full potential. Keywords: nanoparticles, tissue engineering, antibacterial applications, mechanotransduction, gene deliver

Therapeutic potential of human olfactory bulb neural stem cells for spinal cord injury in rats.

STUDY DESIGN: Adult human olfactory bulb neural stem cells (OBNSCs) were isolated from human patients undergoing craniotomy for tumor resection. They were genetically engineered to overexpresses green fluorescent protein (GFP) to help trace them following engraftment. Spinal cord injury (SCI) was induced in rats using standard laminectomy protocol, and GFP-OBNSC were engrafted into rat model of SCI at day 7 post injury. Three rat groups were used: (i) Control group, (ii) Sham group (injected with cerebrospinal fluid) and treated group (engrafted with OBNSCs). Tissues from different groups were collected weekly up to 2 months. The collected tissues were fixed in 4% paraformaldehyde, processed for paraffin sectioning, immunohistochemically stained for different neuronal and glial markers and examined with bright-field fluorescent microscopy. Restoration of sensory motor functions we assessed on a weekly bases using the BBB score. OBJECTIVES: To assess the therapeutic potential of OBNSCs-GFP and their ability to survive, proliferate, differentiate and to restore lost sensory motor functions following their engraftment in spinal cord injury (SCI). METHODS: GFP-OBNSC were engrafted into a rat model of SCI at day 7 post injury and were followed-up to 8 weeks using behavioral and histochemical methods. RESULTS: All transplanted animals exhibited successful engraftment. The survival rate was about 30% of initially transplanted cells. Twenty-seven percent of the engrafted cells differentiated along the NG2 and O4-positive oligodendrocyte lineage, 16% into MAP2 and β-tubulin-positive neurons, and 56% into GFAP-positive astrocytes. CONCLUSION: GFP-OBNSCs had survived for >8 weeks after engraftment and were differentiated into neurons, astrocytes and oligodendrocytes, The engrafted cells were distributed throughout gray and white matter of the cord with no evidence of abnormal morphology or any mass formation indicative of tumorigenesis. However, the engrafted cells failed to restore lost sensory and motor functions as evident from behavioral analysis using the BBB score test.BRC, Q

Aspirin inhibits proliferation and promotes differentiation of neuroblastoma cells via p21Waf1 protein up-regulation and Rb1 pathway modulation.

Several clinical and experimental studies have demonstrated that regular use of aspirin (acetylsalicylic acid, ASA) correlates with a reduced risk of cancer and that the drug exerts direct anti-tumour effects. We have previously reported that ASA inhibits proliferation of human glioblastoma multiforme-derived cancer stem cells. In the present study, we analysed the effects of ASA on nervous system-derived cancer cells, using the SK-N-SH (N) human neuroblastoma cell line as an experimental model. ASA treatment of SK-N-SH (N) dramatically reduced cell proliferation and motility, and induced neuronal-like differentiation, indicated by the appearance of the neuronal differentiation marker tyrosine hydroxylase (TH) after 5 days. ASA did not affect cell viability, but caused a time-dependent accumulation of cells in the G0 /G1 phase of the cell cycle, with a concomitant decrease in the percentage of cells in the G2 phase. These effects appear to be mediated by a COX-independent mechanism involving an increase in p21Waf1 and underphosphorylated retinoblastoma (hypo-pRb1) protein levels. These findings may support a potential role of ASA as adjunctive therapeutic agent in the clinical management of neuroblastoma

PDGF receptor alpha inhibition induces apoptosis in glioblastoma cancer stem cells refractory to anti-Notch and anti-EGFR treatment

Cancer stem cells (CSC) represent a rare fraction of cancer cells characterized by resistance to chemotherapy and radiation, therefore nowadays there is great need to develop new targeted therapies for brain tumors and our study aim to target pivotal transmembrane receptors such as Notch, EGFR and PDGFR, which are already under investigation in clinical trials setting for the treatment of Glioblastoma Multiforme (GBM)

Gene expression profile of adult human olfactory bulb and embryonic neural stem cell suggests distinct signaling pathways and epigenetic control

Global gene expression profiling was performed using RNA from human embryonic neural stem cells (hENSC), and adult human olfactory bulb-derived neural stem cells (OBNSCs), to define a gene expression pattern and signaling pathways that are specific for each cell lineage. We have demonstrated large differences in the gene expression profile of human embryonic NSC, and adult human OBNSCs, but less variability between parallel cultures. Transcripts of genes involved in neural tube development and patterning (ALDH1A2, FOXA2), progenitor marker genes (LMX1a, ALDH1A1, SOX10), proliferation of neural progenitors (WNT1 and WNT3a), neuroplastin (NPTN), POU3F1 (OCT6), neuroligin (NLGN4X), MEIS2, and NPAS1 were up-regulated in both cell populations. By Gene Ontology, 325 out of 3875 investigated gene sets were scientifically different. 41 out of the 307 investigated Cellular Component (CC) categories, 45 out of the 620 investigated Molecular Function (MF) categories, and 239 out of the 2948 investigated Biological Process (BP) categories were significant. KEGG Pathway Class Comparison had revealed that 75 out of 171 investigated gene sets passed the 0.005 significance threshold. Levels of gene expression were explored in three signaling pathways, Notch, Wnt, and mTOR that are known to be involved in NS cell fates determination. The transcriptional signature also deciphers the role of genes involved in epigenetic modifications. SWI/SNF DNA chromatin remodeling complex family, including SMARCC1 and SMARCE1, were found specifically up-regulated in our OBNSC but not in hENSC. Differences in gene expression profile of transcripts controlling epigenetic modifications, and signaling pathways might indicate differences in the therapeutic potential of our examined two cell populations in relation to in cell survival, proliferation, migration, and differentiation following engraftments in different CNS insults

Gene expression profile of adult human olfactory bulb and embryonic neural stem cell suggests distinct signaling pathways and epigenetic control

Global gene expression profiling was performed using RNA from human embryonic neural stem cells (hENSC), and adult human olfactory bulb-derived neural stem cells (OBNSCs), to define a gene expression pattern and signaling pathways that are specific for each cell lineage. We have demonstrated large differences in the gene expression profile of human embryonic NSC, and adult human OBNSCs, but less variability between parallel cultures. Transcripts of genes involved in neural tube development and patterning (ALDH1A2, FOXA2), progenitor marker genes (LMX1a, ALDH1A1, SOX10), proliferation of neural progenitors (WNT1 and WNT3a), neuroplastin (NPTN), POU3F1 (OCT6), neuroligin (NLGN4X), MEIS2, and NPAS1 were up-regulated in both cell populations. By Gene Ontology, 325 out of 3875 investigated gene sets were scientifically different. 41 out of the 307 investigated Cellular Component (CC) categories, 45 out of the 620 investigated Molecular Function (MF) categories, and 239 out of the 2948 investigated Biological Process (BP) categories were significant. KEGG Pathway Class Comparison had revealed that 75 out of 171 investigated gene sets passed the 0.005 significance threshold. Levels of gene expression were explored in three signaling pathways, Notch, Wnt, and mTOR that are known to be involved in NS cell fates determination. The transcriptional signature also deciphers the role of genes involved in epigenetic modifications. SWI/SNF DNA chromatin remodeling complex family, including SMARCC1 and SMARCE1, were found specifically up-regulated in our OBNSC but not in hENSC. Differences in gene expression profile of transcripts controlling epigenetic modifications, and signaling pathways might indicate differences in the therapeutic potential of our examined two cell populations in relation to in cell survival, proliferation, migration, and differentiation following engraftments in different CNS insults