The Phenotype and Functional Activity of Mesenchymal Stromal Cells in Pediatric Patients with Non-Malignant Hematological Diseases

Abstract

As the biology of mesenchymal stromal cells (MSCs) in patients with non-malignant hematological diseases (NMHD) is poorly understood, in the current study we performed a basic characterization of the phenotype and functional activity of NMHD-MSCs. Bone marrow (BM) of patients with thalassemia major (TM) possessed a significantly higher number of nucleated cells (BM-MNCs)/mL BM than healthy donors (P < 0.0001), which however did not result in a higher number of colony forming units-fibroblast (CFU-F) per milliliter BM. In contrast, from 1 × 106 BM-MNCs of patients with sickle cell disease (SCD) were generated significantly more CFU-Fs than from TM-BM-MNCs (P < 0.013) and control group (P < 0.02). In addition, NMHD-MSCs expressed significantly lower levels of CD146 molecule, demonstrated an equal proliferation potential and differentiated along three lineages (osteoblasts, chondrocytes and adipocytes) as healthy donors’ MSCs, with exception of TM-MSCs which differentiated weakly in adipocytes. In contrast to other NMHD-MSCs and healthy donors’ MSCs, TM-MSCs demonstrated an impaired in vitro immunosuppressive potential, either. Noteworthy, the majority of the immunosuppressive effect of NMHD-MSCs was mediated through prostaglandin-E2 (PGE2), because indomethacin (an inhibitor of PGE2 synthesis) was able to significantly reverse this effect. Our results indicate therefore that NMHD-MSCs, except TM-MSCs, may be used as an autologous cell-based therapy for post-transplant complications such as graft failure, graft-versus-host disease (GvHD) and osteonecrosis.

Quantification and Comprehensive Analysis of Mesenchymal Stromal Cells in Bone Marrow Samples from Sickle Cell Disease Patients with Osteonecrosis

“…Microscopical analysis demonstrated that CFU-Fs exhibited intra- and interdonor heterogeneity in both SCD and NS groups, with either large or small colonies formed by fibroblastoid cells ( Figure 1(e) ). These findings indicate an effective enrichment of CFU-F in BM-MNC samples from patients with osteonecrosis, which is consistent with previous reports [ 8 , 35 ].…”

Senescent mesenchymal stem/stromal cells and restoring their cellular functions

“…These studies include both preclinical and clinical trials of either autologous or allogeneic MSCs. Infusion of MSCs has been performed to evaluate their safety and therapeutic efficacy in diseases of the immune[ 3 ], hematological[ 4 ], cardiovascular[ 5 , 6 ], nervous[ 7 , 8 ], respiratory[ 9 ], digestive[ 10 ], skeletal[ 11 ], endocrine[ 12 ], and reproductive[ 13 ] systems[ 14 ]. To date, more than 1000 MSC-based clinical trials have been registered in the United States National Institute of Health database[ 15 , 16 ].…”