Current Issue : April - June Volume : 2012 Issue Number : 2 Articles : 8 Articles
Human induced pluripotent stem cells (hiPSCs) have core properties of unlimited self-renewal and differentiation potential and\nhave emerged as exciting cell sources for applications in regenerative medicine, drug discovery, understanding of development,\nand disease etiology. Key among numerous criteria to assess pluripotency includes the in vivo teratoma assay that has been widely\nproposed as a standard functional assay to demonstrate the pluripotency of hiPSCs. Yet, the lack of reliability across methodologies,\nlack of definitive clinical significance, and associated expenses bring into question use of the teratoma assay as the ââ?¬Å?gold standardââ?¬Â\nfor determining pluripotency.We propose use of the in vitro embryoid body (EB) assay as an important alternative to the teratoma\nassay. This paper summarizes the methodologies for creating EBs from hiPSCs and the subsequent analyses to assess pluripotency\nand proposes its use as a cost-effective, controlled, and reproducible approach that can easily be adopted to determine pluripotency\nof generated hiPSCs....
Intervertebral disc degeneration (IVD) is a frequent pathological condition. Conservative management often fails, and patients\r\nwith IVD degeneration may require surgical intervention. Several treatment strategies have been proposed, although only surgical\r\ndiscectomy and arthrodesis have been proved to be predictably effective. The aim of biological strategies is to prevent and manage\r\nIVD degeneration, improve the function, the anabolic and reparative capabilities of the nucleus pulposus and annulus fibrosus\r\ncells, and inhibit matrix degradation. At present, clinical applications are still in their infancy. Further studies are required to\r\nclarify the role of mesenchymal stem cells and gene therapy for the prevention and treatment of IVD degeneration....
While small bone defects heal spontaneously, large bone defects need surgical intervention for bone transplantation. Autologous\r\nbone grafts are the best and safest strategy for bone repair. An alternative method is to use allogenic bone graft. Both methods\r\nhave limitations, particularly when bone defects are of a critical size. In these cases, bone constructs created by tissue engineering\r\ntechnologies are of utmost importance. Cells are one main component in the manufacture of bone construct. A few cell types,\r\nincluding embryonic stem cells (ESCs), adult osteoblast, and adult stem cells, can be used for this purpose. Mesenchymal stem\r\ncells (MSCs), as adult stem cells, possess characteristics that make them good candidate for bone repair. This paper discusses\r\ndifferent aspects of MSCs that render them an appropriate cell type for clinical use to promote bone regeneration....
The development of the vascular system begins with the formation of hemangioblastic cells, hemangioblasts, which organize\nin blood islands in the yolk sac. The hemangioblasts differentiate into hematopoietic and angioblastic cells. Subsequently, the\nhematopoietic line will generate blood cells, whereas the angioblastic cells will give rise to vascular endothelial cells (ECs). In\nresponse to specific molecular and hemodynamic stimuli, ECs will acquire either arterial or venous identity. Recruitment towards\nthe endothelial tubes and subsequent differentiation of pericyte and/or vascular smooth muscle cells (vSMCs) takes place and\nthe mature vessel is formed. The Notch signaling pathway is required for determining the arterial program of both endothelial\nand smooth muscle cells; however, it is simultaneously involved in the generation of hematopoietic stem cells (HSCs), which will\ngive rise to hematopoietic cells. Notch signaling also regulates the function of endothelial progenitor cells (EPCs), which are bonemarrow-\nderived cells able to differentiate into ECs and which could be considered the adult correlate of the angioblast. In addition,\nNotch signaling has been reported to control sprouting angiogenesis during blood vessels formation in the adult. In this paper we\ndiscuss the physiological role of Notch in vascular development, providing an overview on the involvement of Notch in vascular\nbiology from hematopoietic stem cell to adaptive neovascularization in the adult....
Adult mesenchymal stem cells (MSCs) are being investigated further for their use in stem cell therapies. However, as they are\nfound in very low numbers in adult tissue, expansion in vitro is required to produce desired MSC numbers for clinical application.\nThe need for effective cell-based therapies is increasing due to a rise in the ageing population, increasing the prevalence of\nmusculoskeletal disorders. This review investigates how factors, age and gender of donor, as well as seeding density can affect MSC\nexpansion. Age and gender of donor have received mixed results from studies, whereas seeding density studies have produced\nconsistent results for numerous MSC sources, favouring lower seeding densities. Further research is required to reduce the risk of\ninfection, loss of cell characterisation in cell culture, and making cell-based therapies more cost effective through creating rapid\nexpansion of MSCs regardless of patient factors....
In genetic diseases, where the cells are already damaged, the damaged cells can be replaced by new normal cells, which can be\r\ndifferentiated from iPSC. To avoid immune rejection, iPSC from the patient�s own cell can be developed. However, iPSC from the\r\npatients�s cell harbors the same genetic aberration. Therefore, before differentiating the iPSCs into required cells, genetic repair\r\nshould be done. This review discusses the various technologies to repair the genetic aberration in patient-derived iPSC, or to\r\nprevent the genetic aberration to cause further damage in the iPSC-derived cells, such as Zn finger and TALE nuclease genetic\r\nediting, RNA interference technology, exon skipping, and gene transfer method. In addition, the challenges in using the iPSC and\r\nthe strategies to manage the hurdles are addressed....
Tendon injuries are a common cause of morbidity and a significant health burden on society. Tendons are structural tissues\r\nconnecting muscle to bone and are prone to tearing and tendinopathy, an overuse or degenerative condition that is characterized\r\nby failed healing and cellular depletion. Current treatments, for tendon tear are conservative, surgical repair or surgical scaffold\r\nreconstruction. Tendinopathy is treated by exercises, injection therapies, shock wave treatments or surgical tendon debridement.\r\nHowever, tendons usually heal with fibrosis and scar tissue, which has suboptimal tensile strength and is prone to reinjury, resulting\r\nin lifestyle changes with activity restriction. Preclinical studies show that cell therapies have the potential to regenerate rather\r\nthan repair tendon tissue, a process termed tenogenesis. A number of different cell lines, with varying degrees of differentiation,\r\nhave being evaluated including stem cells, tendon derived cells and dermal fibroblasts. Even though cellular therapies offer some\r\npotential in treating tendon disorders, there have been few published clinical trials to determine the ideal cell source, the number\r\nof cells to administer, or the optimal bioscaffold for clinical use....
Mouse embryonic fibroblasts (MEFs) and human foreskin fibroblasts (hFFs) are commonly used as feeder cells to maintain the\r\npluripotent state of stem cells. The aim of the present study was to evaluate the effect of MEF and hFF feeders on the cardiac\r\ndifferentiation. Two human embryonic and two induced pluripotent stem cell lines were cultured on MEF and hFF before cardiac\r\ndifferentiation. The expression of Brachyury T was higher in cell lines cultured on MEF, than if cultured on hFF, suggesting\r\nenhanced mesoderm formation. However, significant positive influence of MEF feeders on cardiac differentiation was only seen\r\nwith one cell line. Further, the ability of hFF to maintain pluripotency of stem cells originally cultured on MEF was quite poor.\r\nIn conclusion, the cells behaved differently whether cultured on hFF or MEF feeders. However, the influence of the feeder cells on\r\ndifferentiation was less than the difference observed between the cell lines....
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