Abstract
Human mesenchymal stem cells (MSCs) have an intrinsic property for homing towards tumor sites and can be used as tumor-tropic vectors for tumor therapy. But very limited studies investigated the antitumor properties of MSCs themselves. In this study we investigated the antiglioma properties of two easily accessible MSCs, namely, human adipose tissue-derived mesenchymal stem cells (ASCs) and umbilical cord-derived mesenchymal stem cells (UC-MSCs). We found (1) MSC conditioned media can significantly inhibit the growth of human U251 glioma cell line; (2) MSC conditioned media can significantly induce apoptosis in human U251 cell line; (3) real-time PCR experiments showed significant upregulation of apoptotic genes of both caspase-3 and caspase-9 and significant downregulation of antiapoptotic genes such as survivin and XIAP after MSC conditioned media induction in U 251 cells; (4) furthermore, MSCs conditioned media culture induced rapid and complete differentiation in U251 cells. These results indicate MSCs can efficiently induce both apoptosis and differentiation in U251 human glioma cell line. Whereas UC-MSCs are more efficient for apoptosis induction than ASCs, their capability of differentiation induction is not distinguishable from each other. Our findings suggest MSCs themselves have favorable antitumor characteristics and should be further explored in future glioma therapy.
Highlights
Gliomas are the most common malignant cancer affecting the central nervous system, with a very poor prognosis, in particular with high-grade tumors such as glioblastoma multiforme [1,2,3]
There are some preliminary experiments showing that Mesenchymal stem cells (MSCs) can suppress human glioma growth [18], but the exact mechanisms remain poorly studied. To further explore this phenomenon, we examined the interaction of two different types of mesenchymal stem cells, namely, human adipose tissue-derived mesenchymal stem cells (ASCs) and umbilical cord-derived mesenchymal stem cells (UC-MSCs), with the U251 human glioma cell line
We found that conditioned media from both types of MSCs can significantly induce apoptosis in U251 cells
Summary
Gliomas are the most common malignant cancer affecting the central nervous system, with a very poor prognosis, in particular with high-grade tumors such as glioblastoma multiforme [1,2,3]. Gliomas usually grow in a highly invasive manner and always infiltrate neighboring tissues and surgical resection rarely removes the tumor completely. Gliomas inevitably recur and cause the death of the patient. Radiation therapy usually irradiates normal brain tissues surrounding the tumor as well, causing multiple side effects. Chemotherapy is with limited effects, since most chemicals have difficulty in crossing the blood brain barrier [4]. Temozolomide is the most effective chemotherapeutic reagent but can usually prolong the lifespan for only 3–6 months in some patients
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