Bone Marrow Progenitor Cell Mobilization in Diabetes
Condition: Diabetes Mellitus
MeSH terms: Diabetes Mellitus
Study type: Interventional
Phase: Phase 4

Summary: 
      Diabetes mellitus is associated with a significant reduction of circulating progenitor cells
      (CPCs). These include endothelial progenitor cells (EPCs), which are involved in
      cardiovascular homeostasis and repair. A reduction of CPCs in metabolic patients is
      associated with an increased risk of future adverse cardiovascular outcomes. Therefore, ways
      to active stimulate an increase of CPC levels in diabetes are actively pursued.

      Experimental animal studies and preliminary data in humans indicate that a bone marrow defect
      is causally related to the low CPC level in diabetes.

      Our previous data in rats indicate that diabetes reduces the bone marrow responsiveness to
      granulocyte colony-stimulating factor (G-CSF) in terms of progenitor cell mobilization.

      In the present study, we aim at investigating bone marrow responsiveness to pharmacological
      mobilization of CPC in diabetic patients as compared to non-diabetic subjects.
    

Detailed description: 
      Diabetes mellitus is associated with a significant reduction of circulating progenitor cells
      (CPCs). CPCs are defined by the surface expression of the stem cell antigen CD34 and or
      CD133. These cells include endothelial progenitor cells (EPCs), which are involved in
      cardiovascular homeostasis and repair. EPCs are characterized by the co-expression of
      endothelial antigen(s), such as KDR.

      A reduction of CPCs in metabolic patients is associated with an increased risk of future
      adverse cardiovascular outcomes, such as myocardial infarction, stroke, revascularization,
      etc. Therefore, ways to active stimulate an increase of CPC levels in diabetes are actively
      pursued. Indeed, there are several drugs that stimulate CPCs or EPCs, but it is not fully
      clear if they are active also in diabetic patients.

      The mechanisms that account for CPC reduction in diabetes include defective bone marrow
      mobilization, reduced survival and increased homing outside the bloodstream. Experimental
      animal studies and preliminary data in humans indicate that a bone marrow defect is causally
      related to the low CPC level in diabetes.

      Our previous data in rats indicate that diabetes reduces the bone marrow responsiveness to
      G-CSF in terms of c-kit+/Sca-1+ progenitor cell mobilization.

      There is also some experimental evidence in type 2 diabetic rats that a specific form of
      autonomic neuropathy impairs bone marrow mobilization of progenitor cells.

      In the present study, we aim at investigating bone marrow responsiveness to pharmacological
      mobilization of CPC in diabetic patients as compared to non-diabetic subjects.

      Diabetic subjects and control subjects will be administered with a single dose of granulocyte
      colony stimulating factor (G-CSF) and progenitor cells will be quantified before and 24 hours
      after G-CSF administration. Progenitor cells will be analyzed by flow cytometry on the basis
      of the expression of CD34, CD133 and KDR.

      Mean percentage variation of CPCs and EPCs will be compared in diabetic versus non diabetic
      patients to understand whether or not diabetes is associated with a significant defective
      mobilization of progenitor cells.

      As a secondary aim, diabetic patients will be divided in those with and without diabetic
      autonomic neuropathy (DAN) to understand if DAN modulates bone marrow responsiveness to
      G-CSF.
    

Intervention name(s): Filgrastim, hrG-CSF
Intervention type(s): Drug
Intervention description(s): Single subcutaneous injection of Filgrastim (hrG-CSF) 300 microg (30 MU)
Intervention MeSH terms: Lenograstim
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Diabetes; stem cells; bone marrow; mobilization