1. To establish optimized and standardized approaches for the isolation and characterization of BOECs in control and diabetic patients.2. To test whether the phenotype of BOECs cultured from blood of diabetic patients are significantly different…
ID
Source
Brief title
Condition
- Diabetic complications
- Nephropathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Cell metabolism, endothelial maturation markers and angiogenic markers.
Secondary outcome
nvt
Background summary
Micro- and macrovascular complications are the pathological hallmarks of
diabetes mellitus. Diabetic nephropathy is one of the most serious
microvascular complications associated with diabetes and the incidence of type
2 diabetes (T2DM) is rapidly increasing. Despite better regulation of
hyperglycemia and blood pressure, many patients still develop end-stage renal
disease (ESRD). Worldwide, the number of patients with end-stage kidney disease
necessitating dialysis or transplantation is reaching epidemic proportions.
Therefore, innovative models that can advance our understanding of kidney
disease and the potential for endogenous kidney regeneration are warranted.
Currently various attempts are underway to create kidney-organoids using human
pluripotent stem cells (hPSC) and strategies to control and guide the resulting
development of these hPSC-derived kidney tissues will be crucial for future
regenerative medicine applications. One of the main bottlenecks in
differentiation and maturation of each nephrologic segment is early presence of
a competent vasculature. One potential candidate for creation of endothelial
cells is the blood-outgrowth endothelial cell (BOEC).
Study objective
1. To establish optimized and standardized approaches for the isolation and
characterization of BOECs in control and diabetic patients.
2. To test whether the phenotype of BOECs cultured from blood of diabetic
patients are significantly different than the phenotype of cultured BOECS from
healthy persons.
3. To explore whether these BOECs phenotypic changes in diabetes are related
only to environmental cues (plasma) or also results into epigenetic changes.
4. To develop in vitro strategies to use BOECs in the *nephron-on*a*chip* model
to test for vascularization under control or diabetic circumstances.
5. To further develop the nephron*on*a*chip model with a vascularized
glomerulus under control- or diabetic conditions for drug screening, disease
modelling and regenerative kidney medicine.
Study design
The study is a non-therapeutic, basic science, experimental in vitro study that
requires the sampling of venous peripheral blood of the participants for the
isolation of BOECs and plasma. In addition, urine will be collected for
inflammatory marker analysis.
Study burden and risks
The objectives of this study can only be reached by studying diabetes patients
and healthy controls. The participants do not directly benefit from this
research, however the burden is minimal as it is restricted to a venipuncture
of negligible risk.
Participants may be requested for repeating sampling, only after new informed
consent is asked.
Albinusdreef 2
Leiden 2333 ZA
NL
Albinusdreef 2
Leiden 2333 ZA
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible to participate in this study, the following criteria must be met:
- Age 18 years or older.
- Prior diagnosis of type 2 diabetes mellitus.
- Subject is willing to participate in the study, must be able to give informed consent and the consent must be obtained prior to any study procedure.;Healthy Controls
- Age 18 years or older, participants will be age-matched with recruited patients.
- Not known with type 2 diabetes mellitus
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded from participation in this study:
- Any concurrent illness, disability or clinically significant abnormality that may, as judged by the investigator, affect interpretation.
- Non-diabetic renal disease e.g. known polycystic kidney disease.
- Prominent renal deterioration (CKD-EPI *60 ml/min/1.73m² )
- Use of LMW heparin and/or immunosuppressive drugs.
- Signs of active infection or autoimmune disease, requiring systemic treatment.
- A psychiatric, addictive or any disorder that compromises ability to give truly informed consent for participation in this study.
- Use of any investigational drug.
Design
Recruitment
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL64597.058.18 |