Christopher Malcuit
Advanced Cell Technology
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Featured researches published by Christopher Malcuit.
Stem Cells | 2009
Bin Lu; Christopher Malcuit; Shaomei Wang; S. Girman; Peter J. Francis; Linda Lemieux; Robert Lanza; Raymond D. Lund
Assessments of safety and efficacy are crucial before human ESC (hESC) therapies can move into the clinic. Two important early potential hESC applications are the use of retinal pigment epithelium (RPE) for the treatment of age‐related macular degeneration and Stargardt disease, an untreatable form of macular dystrophy that leads to early‐onset blindness. Here we show long‐term functional rescue using hESC‐derived RPE in both the RCS rat and Elov14 mouse, which are animal models of retinal degeneration and Stargardt, respectively. Good Manufacturing Practice‐compliant hESC‐RPE survived subretinal transplantation in RCS rats for prolonged periods (>220 days). The cells sustained visual function and photoreceptor integrity in a dose‐dependent fashion without teratoma formation or untoward pathological reactions. Near‐normal functional measurements were recorded at >60 days survival in RCS rats. To further address safety concerns, a Good Laboratory Practice‐compliant study was carried out in the NIH III immune‐deficient mouse model. Long‐term data (spanning the life of the animals) showed no gross or microscopic evidence of teratoma/tumor formation after subretinal hESC‐RPE transplantation. These results suggest that hESCs could serve as a potentially safe and inexhaustible source of RPE for the efficacious treatment of a range of retinal degenerative diseases. STEM CELLS 2009;27:2126–2135
Investigative Ophthalmology & Visual Science | 2011
Ilene K. Sugino; Qian Sun; Jianqiu Wang; Celia F. Nunes; Noounanong Cheewatrakoolpong; Aprille Rapista; Adam C. Johnson; Christopher Malcuit; Irina Klimanskaya; Robert Lanza; Marco A. Zarbin
PURPOSE To compare RPE derived from human embryonic stem cells (hES-RPE) and fetal RPE (fRPE) behavior on human Bruchs membrane (BM) from aged and AMD donors. METHODS hES-RPE of 3 degrees of pigmentation and fRPE were cultured on BM explants. Explants were assessed by light, confocal, and scanning electron microscopy. Integrin mRNA levels were determined by real-time polymerase chain reaction studies. Secreted proteins in media were analyzed by multiplex protein analysis after 48-hour exposure at culture day 21. RESULTS hES-RPE showed impaired initial attachment compared to fRPE; pigmented hES-RPE showed nuclear densities similar to fRPE at day 21. At days 3 and 7, hES-RPE resurfaced BM to a limited degree, showed little proliferation (Ki-67), and partial retention of RPE markers (MITF, cytokeratin, and CRALBP). TUNEL-positive nuclei were abundant at day 3. fRPE exhibited substantial BM resurfacing at day 3 with decreased resurfacing at later times. Most fRPE retained RPE markers. Ki-67-positive nuclei decreased with time in culture. TUNEL staining was variable. Increased integrin mRNA expression did not appear to affect cell survival at day 21. hES-RPE and fRPE protein secretion was similar on equatorial BM except for higher levels of nerve growth factor and thrombospondin-2 (TSP2) by hES-RPE. On submacular BM, fRPE secreted more vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor, and platelet-derived growth factor; hES-RPE secreted more TSP2. CONCLUSIONS Although pigmented hES-RPE and fRPE resurfaced aged and AMD BM to a similar, limited degree at day 21, cell behavior at earlier times was markedly dissimilar. Differences in protein secretion may indicate that hES-RPE may not function identically to native RPE after seeding on aged or AMD BM.
Developments in ophthalmology | 2014
Ilene K. Sugino; Qian Sun; Noounanong Cheewatrakoolpong; Christopher Malcuit; Marco A. Zarbin
Suspensions of human embryonic stem cell-derived retinal pigment epithelium (hES-RPE) and human fetal RPE resurface aged and age-related macular degeneration (AMD) Bruchs membrane to a limited degree at day 21 in organ culture. Survival and differentiation of hES-RPE and human fetal RPE on aged or AMD Bruchs membrane are enhanced greatly (200%) if a biologically synthesized extracellular matrix (bovine corneal endothelial cell extracellular matrix) is laid down on Bruchs membrane prior to transplantation. Transplanted RPE survival is enhanced even more (400-1,000%) if Bruchs membrane is treated with bovine corneal endothelial cell-conditioned medium during organ culture of hES-RPE or fetal RPE on aged or AMD Bruchs membrane. Future efforts are focused on identifying the bioactive components of bovine corneal endothelial cell-conditioned medium, so that this material can be reconstituted for clinical use as an adjunct to improve RPE transplant survival and differentiation in AMD eyes.
Archive | 2011
Raymond L. Page; Christopher Malcuit; Tanja Dominko
Induced pluripotent stem (iPS) cells are embryonic stem-like cells produced by forcing expression of a minimal number of key factors in differentiated somatic cells. In many ways, they are indistinguishable from embryonic stem cells in that they can differentiate into any cell type in the body. This development has led to worldwide excitement over the possibility to develop cell-based therapies for a variety of degenerative diseases using cells derived from and thus genetically matched to the patient they are aimed to treat. This chapter reviews the scientific foundation that has led to the ability to create iPS cells and the current methods used to make them, as well as the studies that have been conducted to help decipher the molecular pathways involved. The evolution of steps developed in recent years to improve both the efficiency and the safety of the process for clinical and in vitro diagnostic use is also presented.
Archive | 2002
Raymond Page; Tanja Dominko; Christopher Malcuit
Archive | 2010
Irina Klimanskaya; Shi-Jiang Lu; Robert Lanza; Michael D. West; Karen Chapman; Roy Geoffrey Sargent; Raymond L. Page; Tanja Dominko; Christopher Malcuit
Archive | 2010
Christopher Malcuit; Linda Lemieux; William Holmes; Pedro Huertas; Lucy Vilner
Archive | 2008
Christopher Malcuit; Linda Lemieux; Willliam Holmes; Pedro Huertas; Lucy Vilner
Archive | 2008
Christopher Malcuit; Linda Lemieux; William Holmes; Pedro Huertas; Lucy Vilner
Archive | 2010
Christopher Malcuit; Linda Lemieux; William Holmes; Pedro Huertas; Lucy Vilner