Relation between the frequency of CD34+ bone marrow derived circulating progenitor cells and the number of diseased coronary arteries in patients with myocardial ischemia and diabetes

Abstract

BackgroundBone marrow-derived circulating progenitor cells (BM-CPCs) in patients with coronary heart disease are impaired with respect to number and mobilization. However, it is unknown whether the mobilization of BM-CPCs depends on the number of diseased coronary arteries. Therefore, in our study, we analysed the correlation between the diseased coronary arteries and the frequency of CD34/45+ BM-CPCs in peripheral blood (PB) in patients with ischemic heart disease (IHD).MethodsThe frequency of CD34/45+ BM-CPCs was measured by flow cytometry in 120 patients with coronary 1 vessel (IHD1, n = 40), coronary 2 vessel (IHD2, n = 40), coronary 3 vessel disease (IHD3, n = 40) and in a control group of healthy subjects (n = 40). There was no significant difference of the total number of cardiovascular risk factors between IHD groups, beside diabetes mellitus (DM), which was significantly higher in IHD3 group compared to IHD2 and IHD1 groups.ResultsThe frequency of CD34/45+ BM-CPCs was significantly reduced in patients with IHD compared to the control group (CD34/45+; p < 0.001). The frequency of BM-CPCs was impaired in patients with IHD3 compared to IHD1 (CD34/45+; p < 0.001) and to IHD2 (CD34/45+; p = 0.001). But there was no significant difference in frequency of BM-CPCs between the patients with IHD2 and IHD1 (CD34/45+; p = 0.28). In a subgroup we observed a significant negative correlation between levels of hemoglobin AIc (HbAIc) and the frequency of BM-CPCs (CD34/45+; p < 0.001, r = -0.8).ConclusionsThe frequency of CD34/45+ BM-CPCs in PB is impaired in patients with IHD. This impairment may augment with an increased number of diseased coronary arteries. Moreover, the frequency of CD34/45+ BM-CPCs in ischemic tissue is further impaired by diabetes in patients with IHD.

Umbilical Cord Blood‐Derived Aldehyde Dehydrogenase‐Expressing Progenitor Cells Promote Recovery from Acute Ischemic Injury

“…First, we have identified a mixed population of hematopoietic/myeloid and nonhematopoietic/endothelial ALDH hi progenitor cells from human UCB as a readily available and clinically applicable cell population with potent proangiogenic function. Second, the potential use of allogeneic UCB cells will open new avenues toward clinical cell-based therapies for ischemic disease, as mounting evidence indicates the potential for progenitor deletion and dysfunction of autologous BM cells in patients with severe diabetes and cardiovascular disease [2,[18][19][20]. Third, we have shown that neither high-level nor permanent engraftment of human cells were necessary to mediate augmentation of perfusion and improved vessel density in vivo.…”

“…Despite advances in pharmacological and surgical management, ischemic disease remains one of the leading causes of morbidity and mortality worldwide [1,2]. Thus, novel therapies to promote the regeneration of damaged vasculature are under intense preclinical investigation [3][4][5].…”

“…Numerous studies have established that a decreased frequency or impaired function of circulating CD133 þ or CD34 þ cells is associated with increased cardiovascular risk in patients with ischemic heart disease and diabetes [2,9,[17][18][19][20]. This, in addition to preclinical data showing the proangiogenic potential of BM-derived cells, has led to a number of clinical trials investigating treatment of cardiac [21][22][23] and limb ischemia [24,25] by transplantation of heterogeneous human BM mononuclear cells (MNCs).…”

Expanded Hematopoietic Progenitor Cells Reselected for High Aldehyde Dehydrogenase Activity Demonstrate Islet Regenerative Functions

“…Due to documented progenitor cell dysfunction in patients with diabetes and vascular comorbidities , use of autologous progenitors to stimulate islet regeneration is predicted to show reduced efficacy . Fortunately, recent government initiatives to HLA‐phenotype and cryopreserve umbilical cord blood (UCB) samples for clinical applications has established a readily available source of allogeneic cells early in ontogeny and untouched by disease‐related pathologies.…”

Isolation of Human Umbilical Cord Blood Aldehyde Dehydrogenase–Expressing Progenitor Cells that Modulate Vascular Regenerative Functions In Vitro and In Vivo

“…Ischemic disease is characterized by the reduction of blood flow to the heart or peripheral tissues and encompasses life‐threatening disorders such as ischemic heart disease and critical limb ischemia. Despite advances in the management of these conditions, ischemic disease remains a leading causes of morbidity and mortality worldwide (Dotsenko, ; Bozdag‐Turan et al, ). Thus, exogenous stimulation of blood vessel formation by cell transplantation is under intense investigation for the treatment of ischemic disease.…”