Microgravity culture conditions decrease immunogenicity but maintain excellent morphology of pancreatic islets

Rutzky, Lynne P.; Kloc, Małgorzata; Biliński, S; Phan, T.; Zhang, H.; Stepkowski, S. M.; Katz, Stephen M.

doi:10.1016/s0041-1345(00)02799-8

Cited by 11 publications

(3 citation statements)

References 2 publications

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“…These changes in the differentiated state of isolated islets prior to and following transplantation are suggested to lead to the failure of islets to restore glucohomeostasis in a significant population of transplant recipients. [9][10][11][12][13] This model could, therefore, provide valuable insight into the control of adult islet cell differentiation.…”

Section: Introductionmentioning

confidence: 99%

Signals for death and differentiation: a two-step mechanism for in vitro transformation of adult islets of Langerhans to duct epithelial structures

Lipsett

Hazrati

et al. 2003

Cell Death Differ

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Phenotypic change of adult pancreatic islets has been implicated in the development of certain pancreatic cancers and in islet transplant failure. The aim of this study was to characterize intracellular events that mediate changes in adult islet phenotype. Using an in vitro islet-to-duct transformation model, canine islets were induced to undergo phenotypic transformation to duct-like epithelial structures through a two-stage process. Stage one was characterized by widespread islet cell apoptosis associated with the formation of cavitary spaces within the islets. During this stage, c-Jun Nterminal regulated kinase (JNK) and caspase-3 activities were elevated, while extracellular signal-regulated kinase (ERK) and Akt activities were decreased. The second stage of the process was characterized by an inversion in the balance in activity between these signal transduction pathways and by a concomitant decrease in apoptosis. The transformed islets were no longer immunoreactive for islet cell hormones, but expressed the duct epithelial cell marker CK-AE1/AE3. In contrast to islet cells, these duct epithelial cells were highly proliferative. To clarify the role of the identified changes in signal transduction events, we performed additional studies using pharmacological inhibitors of enzyme activity and demonstrated that inhibition of JNK and caspase-3 activity prevented cystic transformation. Our results indicate that the balance in signaling activity between ERK/Akt and JNK/ caspase-3 appears to be an important regulator of islet cell death and differentiation.

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Section: Introductionmentioning

confidence: 99%

Signals for death and differentiation: a two-step mechanism for in vitro transformation of adult islets of Langerhans to duct epithelial structures

Lipsett

Hazrati

et al. 2003

Cell Death Differ

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“…Cells are more differentiated and thus, rotating bioreactors are more suitable for the growth and maintenance of construction of functional tissue than static systems (12)(13)(14)(15)(16).…”

Section: Proliferation Of Keratocytes Under Simulated Microgravity 727mentioning

confidence: 99%

“…Many cell types and tissues were successfully cultured under simulated microgravity conditions, such as the construction of three-dimensional fibroblastpolymer tissues (17), intestinal epithelial organoids (18), and so on (14).…”

Section: Proliferation Of Keratocytes Under Simulated Microgravity 727mentioning

confidence: 99%

Morphological Characteristics and Proliferation of Keratocytes Cultured Under Simulated Microgravity

Chen

Gao

2007

Artificial Organs

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This study probed the changes of keratocytes cultured under simulated microgravity. Keratocytes were isolated from rabbit corneas using collagenase digestion method. Cells were seeded in a 55-mL capacity high-aspect-ratio vessel (HARV) of rotary cell culture system (RCCS) at a density of 1 x 10(4) cells/mL. Dehydrated bovine acellular corneal stroma (5 x 5 x 1 mm, n = 30) was used as a carrier for keratocyte culture. Rotational speed was set at 15, 20, and 30 rpm in the first, second, and third week of culture, respectively. Histological evaluation showed that keratocytes in simulated microgravity culture grew into carriers, but those under conventional gravity grew on the surface of carriers. Scanning electron microscopic evaluation showed that after 19 days in culture, keratocytes on the carriers were spherical and spread in the spaces among the collagen fibers. Cells were dendritic or spindle shaped, and they developed many foot processes linked with surrounding cells. The absorbance values of the simulated microgravity group were significantly higher (P < 0.01) than that of the conventional group from 10 to 19 days of culture. The RCCS obviously enhanced the proliferation of rabbit keratocytes and facilitated the cells' growth into or on the dehydrated bovine acellular corneal stroma. Cells showed more natural morphology.

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Advances in islet transplantation and the UK islet transplant consortium

Paget

Downing

2003

Pract Diab Int

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Islet transplantation has surpassed whole pancreas transplantation as a cure for diabetes mellitus since the success of the Edmonton group. It is a safer procedure and requires minimal surgical intervention, yet offers excellent results in terms of achieving insulin independence. It also offers a more physiological insulin profile than current insulin replacement therapy. The UK Islet Transplant Consortium, founded by Diabetes UK, is in the process of establishing a programme of clinical islet transplantation in the UK.The immunosuppression required to protect islet grafts remains a threat to the long‐term health of transplant recipients and research into the possibility of circumventing the need for immunosuppression continues. The main areas under investigation include immunoisolation of islet grafts, HLA class II mismatching between donor and recipient, destruction of immune‐reactive dendritic cells in culture, in vitro pre‐treatment of islets to reduce their immunogenicity and genetic modification of islets to produce localised immunosuppression and prevent the release of MHC molecules.Because of the shortage of donors, researchers are looking toward alternative sources of glucose‐responsive insulin‐secreting tissue. Xenotransplantation would offer an attractive solution if the risk of transferring animal endogenous retroviruses can be eliminated. The expansion of mature beta‐cells, beta‐cell progenitors in pancreatic ducts or embryonic stem cells into viable tissue for transplant is also being researched in the hope of finding a solution for the tissue shortage issue. Encouraging advances have been made in many of these areas, creating a sense of anticipation and excitement for the future. Copyright © 2003 John Wiley & Sons, Ltd.

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Microgravity culture conditions decrease immunogenicity but maintain excellent morphology of pancreatic islets

Cited by 11 publications

References 2 publications

Signals for death and differentiation: a two-step mechanism for in vitro transformation of adult islets of Langerhans to duct epithelial structures

Signals for death and differentiation: a two-step mechanism for in vitro transformation of adult islets of Langerhans to duct epithelial structures

Morphological Characteristics and Proliferation of Keratocytes Cultured Under Simulated Microgravity

Advances in islet transplantation and the UK islet transplant consortium

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