Expression profile of cancer‐related genes in human adult bone marrow–derived neural stemlike cells highlights the need for tumorigenicity study

Abstract

Human adult bone marrow-derived neural stemlike cells (MDNSCs) may serve as ideal seed cells for cell replacement therapy for human neurological disorders and injuries. However, the long-term safety of this cell population after transplantation must be thoroughly explored before clinical application, and tumorigenicity is a major concern. In this study, we generated MDNSCs capable of forming neurospherelike aggregates and with the potency to differentiate into neural lineage cells in vitro and investigated hundreds of cancer-related genes in MDNSCs in order to determine whether there were any characteristics that could help in the evaluation of their tumorigenic potential. According to the results of testing by PCR and DNA sequencing, there were no mutations at the frequent mutation sites of tumor-suppressor genes p53, p16, and Rb1. Of the 440 cancer-related genes covered by Oligo GEArray Human Cancer Microarray OHS-802, 63 were found to be significantly overexpressed compared with that in fresh normal human adult bone marrow depleted of red blood cells (RBCs). In particular, the overexpressed genes included those promoting cell proliferation and cell invasion and metastasis and members of several oncogenic signaling pathways. The overexpression of MYC, MMP2, Notch2, STC1, ITGA3, STAT5b, RhoC, and Wnt1 was also revealed by quantitative real-time RT-PCR. Because it has been shown that activation of some of these genes promote tumorigenesis, our findings highlight the need for further studies of long-term tumorigenicity in MDNSCs.

Effects of Differentiated Versus Undifferentiated Adipose Tissue-derived Stromal Cell Grafts on Functional Recovery After Spinal Cord Contusion

“…The procedure for immunocytochemistry has been described previously (Zhu et al 2007). The primary antibodies (all from Chemicon International, Inc. Temecula, CA) were rabbit anti-CD44 antibody (1:400), mouse anti-vimentin antibody (1:500), mouse anti-nestin antibody (1:400), mouse anti-b-tubulin isotype III antibody(1:800), mouse anti-GFAP monoclonal antibody (1:600), and mouse antiMAP2ab (1;400).…”

Human Umbilical Vein-Derived Dopaminergic-Like Cell Transplantation with Nerve Growth Factor Ameliorates Motor Dysfunction in a Rat Model of Parkinson’s Disease

“…The cells were plated in 25 cm 2 tissue culture flasks at the density of (1-2) 9 10 5 /ml and incubated at 37°C in the presence of 5% CO 2 . The culture medium was changed once a week, and the growth factors were supplemented every 2 weeks [12].…”

Altered gene expression and miRNA expression associated with cancerous IEC-6 cell transformed by MNNG

“…The rat Oligo GEArray microarray profiles the expression of 113 genes representative of the six biological pathways involved in transformation and tumorigenesis. It has been applied in many experiments [ 23 , 24 ]. Our results showed that most of the six biological pathways were involved in transformation of IEC-6 cells.…”