The senescence of the immune system contributes considerably to the age-related diseases that are the main causes of death after the age of 65. The heterochronous autologous hematopoietic stem cell transplantation, where healthy autologous bone marrow stem cells are collected from donors while young, cryopreserved for a long period, and reinfused at a later time, has been recently proposed as a method for the prevention of immune senescence and delay of the aging process. After heterochronous reinfusion and homing, these young hematopoietic stem cells home in the stem cell niches, where they participate in normal hemato- and immunopoiesis, and improve several immune functions by expanding the immune- and hematopoietic cell repertoires. Although some animal studies confirmed the feasibility of this procedure and extended the longevity of the treated animals, translation to human medicine is much more complex. The question remains whether the heterochronous autologous hematopoietic stem cell transplantation will in fact prevent or mitigate age-related immune defects in a manner that will also extend the healthy life span in humans. In this review, we discuss translational aspects of this procedure and describe further research needed to use this heterochronous methodology.
COBISS.SI-ID: 34381529
Objectives. Cell-based therapy has emerged as a promising strategy for the treatment of patients withheart failure. Increasing evidence supports the hypothesis that paracrine mechanisms mediated by sol-uble factors released by the cells play a predominate role in reparative processes. The aim of our studywas to analyze which cytokines are released by CD34+enriched cell products intended for autologoustransendocardial CD34+cell transplantation in patients with cardiomyopathy. Material and methods. The peripheral blood CD34+cells from 12 patients were mobilized with granu-locyte colony-stimulating factor, collected via apheresis and enriched by immunoselection. Results. In CD34+enriched cell population, hematopoietic, but not mesenchymal or endothelial, pro-genitors were detected. Except for angiopoietin-1, other measured cytokines (FGF1, FGF2, VEGF, PDGF,IL-6, HGH, SDF-1/CXCL12, NRG1) were not released by CD34+cells. The average concentration ofangiopoietin-1 released by 5 × 106CD34+cells grown in neutral DMEM medium was 213.6 ± 130.0 pg/mL(range: 74–448 pg/mL). Angiopoietin-1 secretion correlated well with CD34+cell’s capacity for generatingcolonies derived from hematopoietic progenitors (Pearson’s correlation = 0.964; P ( 0.001).Conclusion. – Our study presents angiopoietin-1 as an interesting candidate and suggests future studies toexplore how its release by CD34+cells might impact the success of autologous CD34+cell transplantation.
COBISS.SI-ID: 34233305
In the past, interferon (IFN)-[gamma] and vitamin D3 (vit D3) have both been associated with induction of tolerogenic characteristics in human dendritic cells (DCs). Although there are only a few reports on interdependency of their actions, the interplay between IFN-[gamma] and vit D3 has been clearly demonstrated in certain aspects of immune reactivity. Since both agents have been associated with regulation of immune responses, we set out to examine their functional and mechanistic interactions in context of principal regulators of immunity, the DCs. Combined treatment with vit D3 and IFN-[gamma] caused an extensive expression of immunoglobulin-like transcript (ILT)-3 and programmed death ligand (PDL)-1 on [gamma]/D3DCs, significantly greater than that caused by vit D3 alone. Such [gamma]/D3DCs retained all general DC characteristics. After CD40 ligand-induced activation, they produced increased amounts of IL-10 with almost absent production of IL-12p70. On the other hand, the co-stimulatory potential of [gamma]/D3DCs was weak, with cells possessing the capacity to inhibit CD4+ T cell, CD8+ T cell, as well as memory T cell responses. Naive CD4+ T cells stimulated with [gamma]/D3DCs produced increased amounts of IL-10 with concomitantly low IFN-[gamma] production, upon T cell receptor activation. Additionally, [gamma]/D3DCs completely inhibited granzyme B expression by CD8+ T cells. The percentage of FoxP3-positive cells in co-cultures with naive CD4+ T cells was...
COBISS.SI-ID: 34566873