Limited specificity of xenoantibodies in diabetic patients transplanted with fetal porcine islet cell clusters. Main antibody reactivity against α-linked galactose-containing epitopes

Abstract Background The transplantation of porcine islet cells provides a new potential therapy to treat patients with type 1 diabetes mellitus (T1DM). Compared to other biomedical technologies, xenotransplantation stands out in terms of its involvement of animals as graft sources, as well as the possible transmission of infectious diseases. As these aspects are especially relevant for potential xenotransplantation recipients, it is important to assess their opinion regarding this technology, in particular in terms of the requirements that should be met in the informed consent process for xenotransplantation. Methods We conducted qualitative interviews with seven T1DM patients to assess their information needs prior to xenotransplantation. Before the interview, the participants received a model informed consent form for a clinical trial with porcine islet cells transplantation. The interviews were transcribed and analysed using qualitative content analysis. Results In the interviews, we identified several requirements that are crucial for patients with T1DM in order to consider xenotransplantation as a potential treatment option: therapy-related requirements, professional care and supervision, successful behaviour and attitude management, improving quality of life, and managing control/self-determination challenges. Regarding the informed consent form, several of the participants’ questions remained open and should be addressed in more detail. The interviewees stressed the importance of personal consultations. Conclusions To become a sustainable therapeutic option, patients especially expected an improved diabetes control and a reduction of diabetes-related burdens. Health-related aspects prove to be pivotal for diabetic patients when considering porcine islet cell transplantation. The use of pigs as source for organ retrievals was not considered as problematic.

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Erastin-induced ferroptosis is a regulator for the growth and function of human pancreatic islet-like cell clusters

Cell Regeneration ◽

10.1186/s13619-020-00055-3 ◽

2020 ◽

Vol 9 (1) ◽

Author(s):

Xing Yu Li ◽

Po Sing Leung

Keyword(s):

Cell Death ◽

Cell Viability ◽

Pancreatic Islet ◽

Islet Cell ◽

Diabetic Patients ◽

Dependent Manner ◽

Pancreatic Islet Cell ◽

Human Pancreatic Islet ◽

Cell Clusters ◽

And Function

AbstractFerroptosis is a newly identified and novel form of cell death, which is characterized by an iron- and reactive oxygen species (ROS)-dependent manner. Potential utility of ferroptotic cell death has been recently proposed for cancer treatment. Meanwhile, ROS generation and apoptosis are inherently consequent to cell apoptosis and dysfunction during islet cell preparation and transplantation. Whether ferroptosis induction is a regulator for cell viability and function in human pancreatic islet-cell clusters (ICCs) derived from pancreatic progenitor cells (PPCs) remains elusive. We thus sought to induce ferroptosis in our established cell culture system of human PPCs/ICCs, examine the effects of ferroptosis on ICCs, and explore the potential regulatory pathways involved. Our results showed that ICCs were prone to the use of ferroptosis-inducing and inhibiting agents under our culture conditions. Erastin, a ferroptosis inducer, was found to trigger ferroptosis in ICCs, without the apparent detection of other types of cell death involved, such as apoptosis and autophagy. In corroboration, the use of ferroptosis inhibitor, ferrostatin-1 (Fer-1), was found to enhance the cell viability of ICCs and prevent them from ferroptosis as well as improve its function. Mechanistically, the erastin-induced ferroptosis in ICCs was probably mediated via activation of JNK/P38/MAPK pathways and upregulation of NOX4 expression. Together, our findings may provide a scientific basis of ferroptosis inhibition as a potential for the amelioration of ICC survival and functionality during islet transplantation in diabetic patients.

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Fetuin-A impairs maturation of pig neonatal islet cell clusters

10.1055/s-0038-1641768 ◽

2018 ◽

Author(s):

F Gerst ◽

AK Fritz ◽

E Lorza Gil ◽

E Wolf ◽

HU Häring ◽

...

Keyword(s):

Islet Cell ◽

Fetuin A ◽

Cell Clusters

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