Topic
Transplantation
About: Transplantation is a research topic. Over the lifetime, 276584 publications have been published within this topic receiving 7961661 citations.
Papers published on a yearly basis
Papers
More filters
TL;DR: The ability of ES cell-derived oligodendrocytes to myelinate axons in culture and to replace lost myelin in the injured adult CNS is demonstrated.
Abstract: Demyelination contributes to the loss of function consequent to central nervous system (CNS) injury. Enhanced remyelination through transplantation of myelin-producing cells may offer a pragmatic approach to restoring meaningful neurological function. An unlimited source of cells suitable for such transplantation therapy can be derived from embryonic stem (ES) cells, which are both pluripotent and genetically flexible. In this paper we show that oligodendrocyte cultures can be reliably produced from retinoic acid-induced ES cells and that these oligodendrocytes can myelinate axons in vitro. Methods were further developed for generating highly enriched cultures of oligodendrocytes through an additional culturing step, producing an intermediate “oligosphere” stage. To test whether ES cells can survive, migrate, and differentiate into mature myelin-producing cells in areas of demyelination in the adult CNS, ES cells were transplanted into the dorsal columns of adult rat spinal cord 3 days after chemical demyelination. In the demyelination site, large numbers of ES cells survived and differentiated primarily into mature oligodendrocytes that were capable of myelinating axons. Furthermore, when oligosphere cells were transplanted into the spinal cords of myelin-deficient shiverer (shi/shi) mutant mice, the ES cell-derived oligodendrocytes migrated into the host tissue, produced myelin and myelinated host axons. These studies demonstrate the ability of ES cell-derived oligodendrocytes to myelinate axons in culture and to replace lost myelin in the injured adult CNS. Transplantation of ES cells may be a practical approach to treatment of primary and secondary demyelinating diseases in the adult CNS.
634 citations
TL;DR: In vitro generation of putative rod and cone photoreceptors from mouse, monkey and human ES cells by stepwise treatments under defined culture conditions, in the absence of retinal tissues, may facilitate the development of human ES cell–based transplantation therapies for retinal diseases.
Abstract: We previously reported the differentiation of mouse embryonic stem (ES) cells into retinal progenitors. However, these progenitors rarely differentiate into photoreceptors unless they are cultured with embryonic retinal tissues. Here we show the in vitro generation of putative rod and cone photoreceptors from mouse, monkey and human ES cells by stepwise treatments under defined culture conditions, in the absence of retinal tissues. With mouse ES cells, Crx+ photoreceptor precursors were induced from Rx+ retinal progenitors by treatment with a Notch signal inhibitor. Further application of fibroblast growth factors, Shh, taurine and retinoic acid yielded a greater number of rhodopsin+ rod photoreceptors, in addition to default cone production. With monkey and human ES cells, feeder- and serum-free suspension culture combined with Wnt and Nodal inhibitors induced differentiation of Rx+ or Mitf+ retinal progenitors, which produced retinal pigment epithelial cells. Subsequent treatment with retinoic acid and taurine induced photoreceptor differentiation. These findings may facilitate the development of human ES cell–based transplantation therapies for retinal diseases.
632 citations
TL;DR: In mice, tumours derived from transplanted human CD271+ melanoma cells were capable of metastatsis in vivo, which helps to explain why T-cell therapies directed at these antigens usually result in only temporary tumour shrinkage.
Abstract: The question of whether tumorigenic cancer stem cells exist in human melanomas has arisen in the last few years. Here we show that in melanomas, tumour stem cells (MTSCs, for melanoma tumour stem cells) can be isolated prospectively as a highly enriched CD271(+) MTSC population using a process that maximizes viable cell transplantation. The tumours sampled in this study were taken from a broad spectrum of sites and stages. High-viability cells isolated by fluorescence-activated cell sorting and re-suspended in a matrigel vehicle were implanted into T-, B- and natural-killer-deficient Rag2(-/-)gammac(-/-) mice. The CD271(+) subset of cells was the tumour-initiating population in 90% (nine out of ten) of melanomas tested. Transplantation of isolated CD271(+) melanoma cells into engrafted human skin or bone in Rag2(-/-)gammac(-/-) mice resulted in melanoma; however, melanoma did not develop after transplantation of isolated CD271(-) cells. We also show that in mice, tumours derived from transplanted human CD271(+) melanoma cells were capable of metastatsis in vivo. CD271(+) melanoma cells lacked expression of TYR, MART1 and MAGE in 86%, 69% and 68% of melanoma patients, respectively, which helps to explain why T-cell therapies directed at these antigens usually result in only temporary tumour shrinkage.
632 citations
TL;DR: Findings indicate that hypoxic cells are a common feature of solid tumors in rodents and provide no evidence that Hypoxic cells should not be present in human tumors.
Abstract: Hypoxic fractions are measured by indirect techniques, which compare the response of tumors to large single doses of radiation given under normal aeration and artificial hypoxia. This paper reviews hypoxic fraction measurements and measurement techniques, giving particular attention to the biological, technical, and statistical aspects of the assays; the implicit assumptions underlying the analyses; and the dependence of the determinations on the assay conditions and the tumor and host characteristics. The three major hypoxic fraction assay techniques (paired survival curve, clamped tumor control, and clamped growth delay) share common biological assumptions. They require that the survival curves of naturally and artificially hypoxic cells have the same slope and intercept. They assume that the majority of the cells are either fully oxic or fully hypoxic. They assume that the methods used to induce artificial hypoxia leave no oxygenated regions and that tumor cells rendered artificially hypoxic are no less viable than cells in normally-aerated tumors. The universal validity of these assumptions is questionable. Each technique uses additional special assumptions and each may measure a different population of hypoxic cells. This paper reviews 92 hypoxic fraction determinations in 42 tumor systems. Radiobiologically hypoxic cells appear to be present in the majority of macroscopic solid rodent tumors. The hypoxic fraction was found to increase as the tumor size increased from microscopic to macroscopic; the dependence of hypoxic fraction on tumor size at macroscopic sizes was less clear. The site of tumor implantation, the use of anesthesia, and certain host characteristics may influence the hypoxic fraction. The hypoxic fraction generally did not depend on the tumor growth rate, transplantation history, or histology. These findings indicate that hypoxic cells are a common feature of solid tumors in rodents and provide no evidence that hypoxic cells should not be present in human tumors.
631 citations
TL;DR: Severe ADAMTS13 deficiency does not detect all patients who may be appropriately diagnosed with TTP-HUS and who may respond to plasma exchange treatment, and many patients in all ADAMts13 activity categories apparently responded to Plasma exchange treatment.
630 citations