Induced pluripotent stem cells (iPSCs) can self-renew indefinitely in culture and differentiate into all specialized cell types including gametes. iPSCs do not exist naturally and are instead generated (“induced” or “reprogrammed”) in culture from somatic cells through ectopic co-expression of defined pluripotency factors. Since they can be generated from any healthy person or patient, iPSCs are considered as a valuable resource for regenerative medicine to replace diseased or damaged tissues. In addition, reprogramming technology has provided a powerful tool to study mechanisms of cell fate decisions and to model human diseases, thereby substantially potentiating the possibility to (i) discover new drugs in screening formats and (ii) treat life-threatening diseases through cell therapy-based strategies. However, various legal and ethical barriers arise when aiming to exploit the full potential of iPSCs to minimize abuse or unauthorized utilization. In this review, we discuss bioethical, legal, and societal concerns associated with research and therapy using iPSCs. Furthermore, we present key questions and suggestions for stem cell scientists, legal authorities, and social activists investigating and working in this field.
In this work, poly(acrylic acid) (PAA) and PAA/multi-walled carbon nanotube (MWNTs) nanofibrous membranes are fabricated by electrospinning to immobilize acetylcholinesterase (AChE).3-Aminopropyltriethoxysilane (APTES) and glutaraldehyde are used for surface modification and PAA membrane stabilization in aqueous media. The structure of the nanofibrous membrane was studied by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, thermogravimetric and mechanical analyses. The AChE enzyme was immobilized on the PAA nanofibers with different amounts of MWNTs concentrations from 0 to 5 wt%. The SEM images revealed that the average diameter of the PAA nanofibers was 226 AE 25 nm which was increased by increasing the MWNTs concentration. The tensile strength and modulus of the nanofibrous membranes increased by 1.87 and 4.39 fold respectively after a crosslinking process. The results show that membranes containing MWNTs are a more appropriate support for enzyme immobilization. In comparison to pure PAA, the activity of the sample containing 4 wt% of MWNTs was increased by 5.07 fold. Also, the immobilized enzyme showed excellent reusability even after 10 cycles of washing and samples maintained more than 90% of their original activities. Moreover, the pH and thermal stability of the immobilized enzyme was improved compared to the free enzyme. The results show that a PAA/MWNTs nanofibrous membrane could be counted as a suitable support for AChE immobilization in addition to different applications such as biosensor manufacturing.
Hybrid surfaces with tunable topography, chemistry, and stiffness have potential to rebuild native extracellular matrix (ECM) and manipulate cell behavior in vitro. However, the fabrication of controllable hybrid surfaces is still challenging. In this study, colloidal self-assembly technology was used to program particles into highly ordered structures with hybrid chemistry and stiffness at biointerfaces. These colloidal self-assembled patterns (cSAPs), including unary, binary, and ternary cSAPs, composed of silicon (Si), polystyrene (PS), and/or poly(N-isopropylacrylamide) (pNIPAM) nanogels (PNGs), were fabricated using either coassembly or layer-by-layer (LBL) methods. The selected binary cSAPs (i.e., PS/PNG and PNG/PS) have a tunable surface topography and wettability between 25 and 37 °C; thus, they can be used as dynamic cell culture substrates. Human adipose-derived mesenchymal stem cells (hASCs), bone marrow-derived mesenchymal stem cells (hBMSCs), and macrophages (THP-1) were investigated on these hybrid cSAPs under a static or dynamic system. The results showed that hybrid cSAPs significantly influenced the focal adhesions, cell morphology, cell migration, and gene expressions of stem cells. In general, stem cells had more vinculin puncta, smaller spreading size, and faster migration speed than the TCPS control. Hybrid cSAPs up-regulated gene expressions of focal adhesion kinase (FAK) and chondrocytes (AGG and SOX9) under static culture, while they also up-regulated osteocytes (COL1 and RUNX2) under dynamic culture. THP-1 macrophages were at M0 state on all cSAPs under static culture. However, cells became sensitive under dynamic culture. For example, some M1 genes (i.e., IL6, CD68, and TNFα) and M2 genes (i.e., IL10 and CD206) were down-regulated, while other M1 genes (i.e., IL1β) and M2 genes (i.e., TGF-β and IL1ra) were up-regulated, depending on the particle combinations. In conclusion, new hybrid cSAPs with thermoresponsive surface properties are versatile materials for stem cells and macrophages manipulation.
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