VEGF, ANGPT1, ANGPT2, and MMP-9 expression in the autologous hematopoietic stem cell transplantation and its impact on the time to engraftment

Abstract

As a site of complicated interactions among cytokines, bone marrow niche has been the subject of many scientific studies, mainly in the context of the proteins influencing damage or recovery of endothelium after allogeneic hematopoietic stem cell transplantation (HSCT). In this study, we aimed at exploring mutual correlations of bone marrow niche cytokines involved in the homing and mobilization of hematopoietic stem cells, as well as in angiogenesis. The aim of our study was to evaluate levels of cytokines: VEGF, angiopoietin-1 (ANGPT1), angiopoietin-2 (ANGPT2), and matrix metalloproteinase 9 (MMP-9) during autologous HSCT and to examine their influence on hematological recovery. Forty-three patients with hematological malignancies (33 multiple myeloma, 10 lymphoma) were enrolled in the study. Plasma samples were taken at five time points: before conditioning treatment (BC), on transplantation day (0) and 7 (+7), 14 (+14), and 21 (+21) days after HSCT. The cytokine levels were evaluated by ELISA method. Our study revealed decreased levels of VEGF, ANGPT1, and MMP-9 in the early post-transplant period as compared to the baseline (BC). ANGPT2 was decreased after conditioning treatment, but tended to increase from day +7. On day +7, positive correlations between ANGPT1 level as well as MMP-9 and the time to engraftment were observed. As opposite to ANGPT1, negative correlation between ANGPT2 level on day +7 after HSCT and the time to hematological recovery was noticed. Our study suggests that investigated cytokines are an important part of bone marrow environment and significantly influence the time to engraftment after HSCT.

miRNA‐15a, miRNA‐16, miRNA‐126, miRNA‐146a, and miRNA‐223 expressions in autologous hematopoietic stem cell transplantation and their impact on engraftment

“…34,36 Positive correlations between the expressions of miRNA-16, of the inflammatory process with increased migration of leukocytes in the direction of the endothelium and adherence to endothelial cells. 52,53 Thus, the increase in the number of leukocytes as a cellular response to the inflammatory process can be significantly controlled by miRNA-223. 35 The processes of migration and adhesion of leukocytes are accompanied by a higher expression of VCAM-1, VEGF, or angiopoietins, which are regulated by miRNA-16, miRNA-126, and miRNA-146a.…”

Advances in Regenerative Medicine and Tissue Engineering: Innovation and Transformation of Medicine

“…The integration of the transplanted graft or scaffold requires that it must self-renew and maintain homeostasis [ 29 , 155 , 156 ]. The most desired source of cells are autologous cells to avoid a host immune response [ 155 , 156 ]. Autologous cells can be passaged in vitro and induced to differentiate into the desired cells before the 3D bioprinting process or transplantation.…”

“…Most 3D bioprinting processes and stem cell therapies require the use of synthetic and natural biological molecules such as growth factors to enhance the proliferation and differentiation of stem cells [ 155 , 301 ]. Reports of severe side effects and toxicity from the use of these substances have surfaced, and scientists are searching for alternatives.…”

The Potential Effect of Medicinal Plants for Cartilage Regeneration

“…Extracted compounds of medicinal plants are usually used as inputs in toxicology, phytochemicals, pharmaceuticals and other chemical industries [3][4][5][7][8][9]. Stem cell therapies involving cartilage regeneration and several current 3D bioprinting processes involve the use of synthetic and natural biological molecules such as growth factors to improve their proliferation and differentiation [9][10][11]. There is an ongoing search in the science community for alternatives of these growth factors and the existing synthetic materials, due to reports on their numerous negative effects and complete failure in cartilage regeneration [3,[12][13][14].…”