Identity, proliferation capacity, genomic stability and novel senescence markers of mesenchymal stem cells isolated from low volume of human bone marrow

Abstract

Human bone marrow mesenchymal stem cells (hBM-MSCs) hold promise for treating incurable diseases and repairing of damaged tissues. However, hBM-MSCs face the disadvantages of painful invasive isolation and limited cell numbers. In this study we assessed characteristics of MSCs isolated from residual human bone marrow transplantation material and expanded to clinically relevant numbers at passages 3-4 and 6-7. Results indicated that early passage hBM-MSCs are genomically stable and retain identity and high proliferation capacity. Despite the chromosomal stability, the cells became senescent at late passages, paralleling the slower proliferation, altered morphology and immunophenotype. By qRT-PCR array profiling, we revealed 13 genes and 33 miRNAs significantly differentially expressed in late passage cells, among which 8 genes and 30 miRNAs emerged as potential novel biomarkers of hBM-MSC aging. Functional analysis of genes with altered expression showed strong association with biological processes causing cellular senescence. Altogether, this study revives hBM as convenient source for cellular therapy. Potential novel markers provide new details for better understanding the hBM-MSC senescence mechanisms, contributing to basic science, facilitating the development of cellular therapy quality control, and providing new clues for human disease processes since senescence phenotype of the hematological patient hBM-MSCs only very recently has been revealed.

Osteogenesis for postoperative temporal bone defects using human ear adipose‐derived stromal cells and tissue engineering: An animal model study

“…19 Although the underlying mechanisms remain unclear, previous reports have suggested that mitochondria, autophagy, genomic stability, and growth factor-mediated changes may affect MSC senescence as the cultivation time and passage number increase. 20,21 In addition, changes in stem cell phenotype may differ depending on the MSC origin, which could significantly impact their clinical potential. 22 Therefore, stemness must be considered before using MSCs for tissue engineering.…”

The transplantation of mesenchymal stem cells derived from unconventional sources: an innovative approach to multiple sclerosis therapy

“…Indeed, it was found that at early passages, human BM-MSCs are genetically stable and retain identity and high proliferation capacity, whereas cells became senescent at late passages. In parallel, the slower proliferation altered morphology and immunophenotype making them more susceptible to cell neoplastic formation concomitantly to a progressive decrease in clonogenicity and differentiation potential (Kundrotas et al 2016). MSCs derived from bone marrow of both murine and human origin have been widely investigated in experimental autoimmune encephalomyelitis (EAE), an induced model of MS.…”

Bone Marrow Stem Cells and Genotoxicity Studies in These Cells: Review

“…[50][51][52][53] Mezenkimal kök hücreler kemik iliği, kordon kanı, trabeküler kemik ve adipoz dokulardan izole edilebilmektedir. [53][54][55] İn vitro ortamda adiposit, osteoblast ve kondroblastlara farklılaşma özellikleri bulunmaktadır.…”