Dysfunction of bone marrow progenitor cells in chronic kidney disease

Dysfunction of bone marrow progenitor cells in chronic kidney disease - Dysfunction of BM progenitor cells in CKD

Status

Active, not recruiting

Phases

Unknown

Study type

Observational

Source

NL-OMON

Registry ID

NL-OMON41569

Enrollment

Registered

2012-10-17

Start date

2013-07-25

Completion date

Unknown

Last updated

2024-04-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

chronic kidney disease chronic renal failure

Interventions

None listed

Eligibility

Age

18 Years to 99 Years

Inclusion criteria

Inclusion criteria: CKD patients/kidney recipients: Inclusion criteria: • CKD patients undergoing renal transplantation procedure • Age>18 yrs • Written informed consent.;Donors/healthy controls: Inclusion criteria: • Healthy controls undergoing renal transplantation donor procedure or voluntarily donate BM during surgery • Age > 18 yrs • Written informed consent.

Exclusion criteria

Exclusion criteria: CKD patients/kidney recipients: Exclusion criteria: 1. Patients undergone stem cell transplantation in the past 2. Based on the exclusion for renal transplantation for CKD: • Active infection (hepatitis B and C, tuberculosis, HIV); • Life expectancy

Design outcomes

Primary

Measure	Time frame
1. Quantify and characterize BM stem and progenitor cells Using flow cytometry, we will quantify the levels of CD34, CD31, KDR, CD133, CD45, CD184, CD140b, CD14 and CD26 positive cells in BM and PB, to determine EPC (CD34, CD31, CD133 and KDR (also known as VEGFR-2)) and stem cells of leukocyte (CD45), stromal cell(CD184, CD26), mesenchymal (CD140b) or monocyte (CD14) origin. BM-cells will be studied for migration-capacity in response to angiogenic factors and for their in vitro capacity to differentiate into EPC. EPC will be studied with respect to proliferative-, adhering-, and angiogenic capacity. Human MSC will be cultured according to clinical protocol in our Gene & Cell Facility. BM-cells, EPC, SPC and MSC from CKD patients and controls will be studied for differences in gene expression and secretion of growth factors. 2.Functional assessment of BM stem and progenitor cells The in vivo neovascularization capacity will be compared of BM cells obtained from patients with CKD and BM cells from healthy controls in a hind limb ischemia animal model. 3.Laboratory testing Laboratory testing will be performed according to the transplantation protocol. In addition we will study progenitor cell mobilizing factors, as well as markers for endothelial cell dysfunction/activation, inflammation and oxidative stress (e.g. Cytokines IL1b, IL2, IL6, SDF, VEGF etc.). BM biopsy The biopsy specimen will be used for histological analysis on the composition and microscopic architecture of the BM.	—

Measure

Time frame

1. Quantify and characterize BM stem and progenitor cells Using flow cytometry, we will quantify the levels of CD34, CD31, KDR, CD133, CD45, CD184, CD140b, CD14 and CD26 positive cells in BM and PB, to determine EPC (CD34, CD31, CD133 and KDR (also known as VEGFR-2)) and stem cells of leukocyte (CD45), stromal cell(CD184, CD26), mesenchymal (CD140b) or monocyte (CD14) origin. BM-cells will be studied for migration-capacity in response to angiogenic factors and for their in vitro capacity to differentiate into EPC. EPC will be studied with respect to proliferative-, adhering-, and angiogenic capacity. Human MSC will be cultured according to clinical protocol in our Gene & Cell Facility. BM-cells, EPC, SPC and MSC from CKD patients and controls will be studied for differences in gene expression and secretion of growth factors. 2.Functional assessment of BM stem and progenitor cells The in vivo neovascularization capacity will be compared of BM cells obtained from patients with CKD and BM cells from healthy controls in a hind limb ischemia animal model. 3.Laboratory testing Laboratory testing will be performed according to the transplantation protocol. In addition we will study progenitor cell mobilizing factors, as well as markers for endothelial cell dysfunction/activation, inflammation and oxidative stress (e.g. Cytokines IL1b, IL2, IL6, SDF, VEGF etc.). BM biopsy The biopsy specimen will be used for histological analysis on the composition and microscopic architecture of the BM.

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Countries

Netherlands

Outcome results