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Yamada K, Shah JA, Tanabe T, Lanaspa MA, Johnson RJ. Xenotransplantation: Where Are We with Potential Kidney Recipients? Recent Progress and Potential Future Clinical Trials. CURRENT TRANSPLANTATION REPORTS 2017; 4:101-109. [PMID: 28989853 DOI: 10.1007/s40472-017-0149-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
PURPOSE Inter-species transplantation, xenotransplantation, is becoming a realistic strategy to solve the organ shortage crisis. Here we focus on seminal publications that have driven research in xenotransplantation, as well as recently published literature and future endeavors. RECENT FINDINGS Advances in gene editing technology have allowed for the efficient production of multi-transgenic porcine donors leading improved xenograft survival in baboons, up to 2-years following heterotopic heart xenotransplantation and from weeks to several months following life-supporting kidney xenotransplanation. As technology evolves, additional challenges have arisen, including the development of proteinuria, early graft loss associated with porcine CMV, disparities in organ growth between donors and recipients as well as high-dose continuous immunosuppression requirements. To address these issues, our laboratory developed a tolerance-inducing protocol which has allowed for >6 months survival of a life-supporting kidney with further approaches currently underway to address the challenges mentioned above. SUMMARY Our recent findings, reviewed in this article, led us to develop methods to overcome obstacles, which, in conjunction with the work of others, are promising for future clinical applications of xenotransplantation.
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Affiliation(s)
- Kazuhiko Yamada
- Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY
| | - Jigesh A Shah
- Transplantation Biology Research Laboratories, Massachusetts general Hospital, Harvard Medical School, Boston, MA
| | - Tatsu Tanabe
- Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY
| | - Miguel A Lanaspa
- Division of Renal Diseases and Hypertension, University of Colorado, Aurora CO
| | - Richard J Johnson
- Division of Renal Diseases and Hypertension, University of Colorado, Aurora CO
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Meng FY, Liu L, Liu J, Li CY, Wang JP, Yang FH, Chen ZS, Zhou P. Hepatocyte isolation from resected benign tissues: Results of a 5-year experience. World J Gastroenterol 2016; 22:8178-8186. [PMID: 27688659 PMCID: PMC5037086 DOI: 10.3748/wjg.v22.i36.8178] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2016] [Revised: 09/01/2016] [Accepted: 09/08/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To analyze retrospectively a 5-year experience of human hepatocyte isolation from resected liver tissues with benign disease.
METHODS We established a method of modified four-step retrograde perfusion to isolate primary human hepatocytes. Samples were collected from the resected livers of patients with intrahepatic duct calculi (n = 7) and liver hemangioma (n = 17). Only the samples weighing ≥ 15 g were considered suitable for hepatocyte isolation. By using the standard trypan blue exclusion technique, hepatocyte viability and yield were immediately determined after isolation.
RESULTS Twenty-four liver specimens, weighing 15-42 g, were immediately taken from the margin of the removed samples and transferred to the laboratory for hepatocyte isolation. Warm ischemia time was 5-35 min and cold ischemia time was 15-45 min. For the 7 samples of intrahepatic duct calculi, the method resulted in a hepatocyte yield of 3.49 ± 2.31 × 106 hepatocytes/g liver, with 76.4% ± 10.7% viability. The 17 samples of liver hemangioma had significantly higher yield of cells (5.4 ± 1.71 × 106 cells/g vs 3.49 ± 2.31 × 106 cells/g, P < 0.05) than the samples of intrahepatic duct calculi. However, there seems to be no clear difference in cell viability (80.3% ± 9.67% vs 76.4% ± 10.7%, P > 0.05). We obtained a cell yield of 5.31 ± 1.87 × 106 hepatocytes/g liver when the samples weighed > 20 g. However, for the tissues weighing ≤ 20 g, a reduction in yield was found (3.08 ± 1.86 × 106 cells/g vs 5.31 ± 1.87 × 106 cells/g, P < 0.05).
CONCLUSION Benign diseased livers are valuable sources for large-number hepatocyte isolation. Our study represents the largest number of primary human hepatocytes isolated from resected specimens from patients with benign liver disease. We evaluated the effect of donor liver characteristics on cell isolation, and we found that samples of liver hemangioma can provide better results than intrahepatic duct calculi, in terms of cell yield. Furthermore, the size of the tissues can affect the outcome of hepatocyte isolation.
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Cheng M, Zhang J, Jiang W, Chen Y, Tian Z. Natural killer cell lines in tumor immunotherapy. Front Med 2012; 6:56-66. [PMID: 22460449 DOI: 10.1007/s11684-012-0177-7] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2011] [Accepted: 11/23/2011] [Indexed: 12/11/2022]
Abstract
Natural killer (NK) cells are considered to be critical players in anticancer immunity. However, cancers are able to develop mechanisms to escape NK cell attack or to induce defective NK cells. Current NK cell-based cancer immunotherapy is aimed at overcoming NK cell paralysis through several potential approaches, including activating autologous NK cells, expanding allogeneic NK cells, usage of stable allogeneic NK cell lines and genetically modifying fresh NK cells or NK cell lines. The stable allogeneic NK cell line approach is more practical for quality-control and large-scale production. Additionally, genetically modifying NK cell lines by increasing their expression of cytokines and engineering chimeric tumor antigen receptors could improve their specificity and cytotoxicity. In this review, NK cells in tumor immunotherapy are discussed, and a list of therapeutic NK cell lines currently undergoing preclinical and clinical trials of several kinds of tumors are reviewed.
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Affiliation(s)
- Min Cheng
- Institute of Immunology, Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei 230027, China
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Mejía-Toiber J, Castillo CG, Giordano M. Strategies for the Development of Cell Lines for Ex Vivo Gene Therapy in the Central Nervous System. Cell Transplant 2011; 20:983-1001. [DOI: 10.3727/096368910x546599] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Disorders of the central nervous system (CNS) as a result of trauma or ischemic or neurodegenerative processes still pose a challenge for modern medicine. Due to the complexity of the CNS, and in spite of the advances in the knowledge of its anatomy, pharmacology, and molecular and cellular biology, treatments for these diseases are still limited. The development of cell lines as a source for transplantation into the damaged CNS (cell therapy), and more recently their genetic modification to favor the expression and delivery of molecules with therapeutic potential (ex vivo gene therapy), are some of the techniques used in search of novel restorative strategies. This article reviews the different approaches that have been used and perfected during the last decade to generate cell lines and their use in experimental models of neuronal damage, and evaluates the prospects of applying these methods to treat CNS disorders.
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Affiliation(s)
- Jana Mejía-Toiber
- Laboratorio de Plasticidad Neuronal, Departamento de Neurobiología Conductual y Cognitiva, Instituto de Neurobiología, Universidad Nacional Autónoma de Mexico, Querétaro, Mexico
| | - Claudia G. Castillo
- Departamento de Bioquímica, Facultad de Medicina, Universidad Autónoma de San Luis Potosí, San Luis Potosí, Mexico
| | - Magda Giordano
- Laboratorio de Plasticidad Neuronal, Departamento de Neurobiología Conductual y Cognitiva, Instituto de Neurobiología, Universidad Nacional Autónoma de Mexico, Querétaro, Mexico
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Cheng M, Ma J, Chen Y, Zhang J, Zhao W, Zhang J, Wei H, Ling B, Sun R, Tian Z. Establishment, characterization, and successful adaptive therapy against human tumors of NKG cell, a new human NK cell line. Cell Transplant 2011; 20:1731-46. [PMID: 21669033 DOI: 10.3727/096368911x580536] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
Natural killer (NK) cells play important roles in adoptive cellular immunotherapy against certain human cancers. This study aims to establish a new human NK cell line and to study its role for adoptive cancer immunotherapy. Peripheral blood samples were collected from 54 patients to establish the NK cell line. A new human NK cell line, termed as NKG, was established from a Chinese male patient with rapidly progressive non-Hodgkin's lymphoma. NKG cells showed LGL morphology and were phenotypically identified as CD56(bright) NK cell with CD16(-), CD27(-), CD3(-), αβTCR(-), γδTCR(-), CD4(-), CD8(-), CD19(-), CD161(-), CD45(+), CXCR4(+), CCR7(+), CXCR1(-), and CX3CR1(-). NKG cells showed high expression of adhesive molecules (CD2, CD58, CD11a, CD54, CD11b, CD11c), an array of activating receptors (NKp30, NKp44, NKp46, NKG2D, NKG2C), and cytolysis-related receptors and molecules (TRAIL, FasL, granzyme B, perforin, IFN-γ). The cytotoxicity of NKG cells against tumor cells was higher than that of the established NK cell lines NK-92, NKL, and YT. NKG cell cytotoxicity depended on the presence of NKG2D and NKp30. When irradiated with 8 Gy, NKG cells were still with high cytotoxicity and activity in vitro and with safety in vivo, but without proliferation. Further, the irradiated NKG cells exhibited strong cytotoxicity against human primary ovarian cancer cells in vitro, and against human ovarian cancer in a mouse xenograft model. The adoptive transfer of NKG cells significantly inhibited the ovarian tumor growth, decreased the mortality rate and prolonged the survival, even in cases of advanced diseases. A number of NKG cells were detected in the ovarian tumor tissues during cell therapy. In use of the new human NK cell line, NKG would a promising cellular candidate for adoptive immunotherapy of human cancer.
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Affiliation(s)
- Min Cheng
- Institute of Immunology, Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, China
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Eve DJ, Fillmore RW, Borlongan CV, Sanberg PR. Stem cell research in cell transplantation: sources, geopolitical influence, and transplantation. Cell Transplant 2010; 19:1493-509. [PMID: 21054954 DOI: 10.3727/096368910x540612] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
If the rapidly progressing field of stem cell research reaches its full potential, successful treatments and enhanced understanding of many diseases are the likely results. However, the full potential of stem cell science will only be reached if all possible avenues can be explored and on a worldwide scale. Until 2009, the US had a highly restrictive policy on obtaining cells from human embryos and fetal tissue, a policy that pushed research toward the use of adult-derived cells. Currently, US policy is still in flux, and retrospective analysis does show the US lagging behind the rest of the world in the proportional increase in embryonic/fetal stem cell research. The majority of US studies being on either a limited number of cell lines, or on cells derived elsewhere (or funded by other sources than Federal) rather than on freshly isolated embryonic or fetal material. Neural, mesenchymal, and the mixed stem cell mononuclear fraction are the most commonly investigated types, which can generally be classified as adult-derived stem cells, although roughly half of the neural stem cells are fetal derived. Other types, such as embryonic and fat-derived stem cells, are increasing in their prominence, suggesting that new types of stem cells are still being pursued. Sixty percent of the reported stem cell studies involved transplantation, of which over three quarters were allogeneic transplants. A high proportion of the cardiovascular systems articles were on allogeneic transplants in a number of different species, including several autologous studies. A number of pharmaceutical grade stem cell products have also recently been tested and reported on. Stem cell research shows considerable promise for the treatment of a number of disorders, some of which have entered clinical trials; over the next few years it will be interesting to see how these treatments progress in the clinic.
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Affiliation(s)
- David J Eve
- Center of Excellence for Aging & Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, Tampa, FL 33612, USA.
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Meng FY, Chen ZS, Han M, Hu XP, He XX, Liu Y, He WT, Huang W, Guo H, Zhou P. Porcine hepatocyte isolation and reversible immortalization mediated by retroviral transfer and site-specific recombination. World J Gastroenterol 2010; 16:1660-4. [PMID: 20355246 PMCID: PMC2848376 DOI: 10.3748/wjg.v16.i13.1660] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To develop a hepatocyte cell line, we immortalized primary porcine hepatocytes with a retroviral vector SSR#69 containing the Simian Virus 40 T antigen (SV40Tag).
METHODS: We first established a method of porcine hepatocyte isolation with a modified four-step retrograde perfusion technique. Then the porcine hepatocytes were immortalized with retroviral vector SSR#69 expressing SV40T and hygromycin-resistance genes flanked by paired loxP recombination targets. SV40T cDNA in the expanded cells was subsequently excised by Cre/LoxP site-specific recombination.
RESULTS: The resultant hepatocytes with high viability (97%) were successfully immortalized with retroviral vector SSR#69. One of the immortalized clones showed the typical morphological appearance, TJPH-1, and was selected by clone rings and expanded in culture. After excision of the SV40T gene with Cre-recombinase, cells stopped growing. The population of reverted cells exhibited the characteristics of differentiated hepatocytes.
CONCLUSION: In conclusion, we herein describe a modified method of hepatocyte isolation and subsequently established a porcine hepatocyte cell line mediated by retroviral transfer and site-specific recombination.
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Shahid JM, Iwamuro M, Sasamoto H, Kubota Y, Seita M, Kawamoto H, Nakaji S, Noguchi H, Yamamoto K, Kobayashi N. Establishment of an immortalized porcine liver cell line JSNK-1 with retroviral transduction of SV40T. Cell Transplant 2010; 19:849-856. [PMID: 20955660 DOI: 10.3727/096368910x508979] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Maintenance of freshly isolated porcine liver cells in vitro is limited for a short period of time. Therefore, establishment of easy handling cell lines is extremely important for in vitro study for liver cells and their possible utilization for cell differentiation and growth of stem cells. Porcine liver cells were transduced with a retroviral vector SSR#69 expressing SV40T, one of SSR#69-immortalized porcine liver cell lines, JSNK-1, was established and characterized. Morphology of JSNK-1 cells was spindle shaped. When the cells became confluent, JSNK-1 cells revealed hills-and-valleys pattern. In the presence of vitamin A, JSNK-1 cells showed big droplets inside the cytoplasm, which were positive with PAS staining. JSNK-1 cells showed the gene expression of collagen type 1α1, collagen type 1α2, FLT-1, β-actin, and SV40T. Immunostaining study revealed that JSNK-1 cells produced collagen, vimentin, and α-smooth muscle actin. JSNK-1 cells possessed the characteristics of the liver stellate cells. JSNK-1 cells produced hepatocyte growth factor (HGF) in a time-dependent manner. When cocultured with iPS cells towards the hepatic differentiation, JSNK-1 cells facilitated their hepatic differentiation in terms of albumin production. In conclusion, JSNK-1 cells would be valuable in the study of liver stellate cell pathophysiology and contribute to the optimization of hepatic differentiation of iPS cells.
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Affiliation(s)
- Javed M Shahid
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
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Iwamuro M, Komaki T, Kubota Y, Seita M, Kawamoto H, Yuasa T, Shahid JM, Hassan RARA, Hassan WARA, Nakaji S, Nishikawa Y, Kondo E, Yamamoto K, Fox IJ, Kobayashi N. Hepatic differentiation of mouse iPS cells in vitro. Cell Transplant 2010; 19:841-847. [PMID: 20955659 DOI: 10.3727/096368910x508960] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
Induced pluripotent stem (iPS) cells are pluripotent and are able to unlimitedly proliferate in vitro. This technical breakthrough in creating iPS cells from somatic cells has noteworthy implications for overcoming the immunological rejection and the ethical issues associated with the derivation of embryonic stem cells from embryos. In the current work, we present an efficient hepatic differentiation of mouse iPS cells in vitro. iPS cells were cultured free floating to induce the formation of embryoid bodies (EB) for 5 days. EB were transferred to a gelatin-coated plate and treated with 100 ng/ml activin A and 100 ng/ml basic fibroblast growth factor (bFGF) for 3 days to induce definitive endoderm. Cells were further cultured for 8 days with 100 ng/ml hepatocyte growth factor (HGF) to generate hepatocytes. Characterization was performed by RT-PCR assay. Functional analysis for albumin secretion and ammonia removal was also carried out. iPS cell-derived hepatocyte-like cells (iPS-Heps) were obtained at the end of the differentiation program. Expression levels of a gestational hepatocyte gene and lineage-specific hepatic genes intensified in iPS-Heps. The production of albumin increased in a time-dependent manner. iPS-Heps were capable of metabolizing ammonia. We present here instant hepatic differentiation of mouse iPS cells using combined 3-day treatments of activin A and bFGF with subsequent 8-day HGF. Our study will be an important step to generate hepatocytes from human iPS cells as a new source for liver-targeted cell therapies.
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Affiliation(s)
- Masaya Iwamuro
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
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Iwamuro M, Komaki T, Kubota Y, Seita M, Kawamoto H, Yuasa T, Shahid JM, Hassan RARA, Hassan WARA, Nakaji S, Nishikawa Y, Kondo E, Yamamoto K, Kobayashi N. Comparative analysis of endoderm formation efficiency between mouse ES cells and iPS cells. Cell Transplant 2010; 19:831-839. [PMID: 20955658 DOI: 10.3727/096368910x508951] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
Definitive endoderm (DE) derived from stem cells holds potential to differentiate into hepatocytes. Stem cell therapy using those cells has potential for a treatment of liver disease. To date, various ways of inducing hepatocytes from embryonic stem (ES) cells have been reported by researchers. However, it has not been proved enough that induced pluripotent stem (iPS) cells behave in the same manner as ES cells in endoderm differentiation. The purpose of this study was to establish an efficient method to induce DE from iPS cells, through comparatively analyzing the efficacy of endoderm formation from mouse ES cells. Furthermore, the efficiency of a serum-free medium in the differentiation into DE was investigated. Mouse ES cells and iPS cells were floated in culture medium for 2 or 5 days and embryoid bodies (EB) were formed. Subsequently, DE was induced with 100 ng/ml activin A and 100 ng/ml basic fibroblast growth factor (bFGF). RT-PCR and real-time PCR analyses were carried out at each step to determine the gene expression of EB markers. The difference in cellular proliferation between serum-containing and serum-free media was examined by an MTS assay in EB and DE induction. iPS cells showed the paralleled mRNA expression to ES cells in each step of differentiation into EB, but the levels of expression of Sox17 and Foxa2 were relatively higher in ES cell-derived DE, whereas Cxcr4 expression was higher in iPS cell-derived DE. The utilization of serum-free medium for iPS cells showed significantly favorable cellular proliferation during EB formation and subsequent DE induction. Forming EB for 5 days and subsequently DE induction with activin A and bFGF with serum-free medium was an appropriate protocol in iPS cells. This may represent an important step for generating hepatocytes from iPS cells for the development of cell therapy.
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Affiliation(s)
- Masaya Iwamuro
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
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Gupta A, Vara D, Punshon G, Sales K, Winslet M, Seifalian A. In vitro small intestinal epithelial cell growth on a nanocomposite polycaprolactone scaffold. Biotechnol Appl Biochem 2009; 54:221-9. [PMID: 19860739 PMCID: PMC2825731 DOI: 10.1042/ba20090214] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2009] [Revised: 10/21/2009] [Accepted: 10/27/2009] [Indexed: 12/05/2022]
Abstract
Tissue engineering of the small intestine remains experimental despite worldwide attempts to develop a functional substitute for short bowel syndrome. Most published studies have reported predominant use of PLLA (poly-L-lactide acid)/PGA (polyglycolic acid) copolymer as the scaffold material, and studies have been limited by in vivo experiments. This lack of progress has inspired a fresh perspective and provoked further investigation and development in this field of tissue engineering. In the present paper, we exploit a relatively new nanocomposite of POSS (polyhedral oligomeric silsesquioxane) and PCL [poly(caprolactone-urea)urethane] as a material to develop porous scaffolds using a solvent casting/particulate leaching technique to fabricate porous scaffolds in different pore sizes and porosities. Scaffolds were characterized for pore morphology and porosity using scanning electron microscopy and micro-computed tomography. Rat intestinal epithelial cells were then seeded on to the polymer scaffolds for an in vitro study of cell compatibility and proliferation, which was assessed by Alamar Blue and lactate dehydrogenase assays performed for 21 days post-seeding. The results obtained demonstrate that POSS-PCL nanocomposite was produced as a macroporous scaffold with porosity over the range of 40-80% and pore size over the range of 150-250 microm. This scaffold was shown to support epithelial cell proliferation and growth. In conclusion, as a further step in investigating small intestinal tissue engineering, the nanocomposite employed in this study may prove to be a useful alternative to poly(lactic-co-glycolic acid) in the future.
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Key Words
- intestinal epithelial cell (iec)
- nanocomposite
- poly(caprolactone-urea)urethane (pcl)
- scaffold
- tissue engineering
- dmac, dimethylacetamide
- ftir, fourier-transform infrared
- iec, intestinal epithelial cell
- ldh, lactate dehydrogenase
- micro-ct, micro-computed tomography
- pcl, poly(caprolactone-urea)urethane
- pcu, poly(carbonate-urea)urethane
- pga, polyglycolic acid
- plga, poly(lactic-co-glycolic acid)
- pn, parenteral
- poss, polyhedral oligomeric silsesquioxane
- sbs, short bowel syndrome
- sem, scanning electron microscopy
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Affiliation(s)
- Ashish Gupta
- *Centre for Nanotechnology, Biomaterials and Tissue Engineering, University College London, London, U.K
- †Gastroenterology Research Group, UCL Division of Surgery and Interventional Science, University College London, London, U.K
| | - Dina S. Vara
- *Centre for Nanotechnology, Biomaterials and Tissue Engineering, University College London, London, U.K
| | - Geoffrey Punshon
- *Centre for Nanotechnology, Biomaterials and Tissue Engineering, University College London, London, U.K
- †Gastroenterology Research Group, UCL Division of Surgery and Interventional Science, University College London, London, U.K
| | - Kevin M. Sales
- ‡Stem Cells Research Group, University College London, London, U.K
| | - Marc C. Winslet
- †Gastroenterology Research Group, UCL Division of Surgery and Interventional Science, University College London, London, U.K
- §Royal Free Hampstead NHS Trust Hospital, London, U.K
- ∥University College London Hospital, London, U.K
| | - Alexander M. Seifalian
- *Centre for Nanotechnology, Biomaterials and Tissue Engineering, University College London, London, U.K
- †Gastroenterology Research Group, UCL Division of Surgery and Interventional Science, University College London, London, U.K
- ‡Stem Cells Research Group, University College London, London, U.K
- §Royal Free Hampstead NHS Trust Hospital, London, U.K
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Affiliation(s)
- Naoya Kobayashi
- Department of Surgery Okayama University Graduate School of Medicine and Dentistry
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