Therapeutic potential of adult bone marrow-derived mesenchymal stem cells Cancer Blood Stem Cell
UroToday.com - adult bone marrow derived from mesenchymal stem cells (MSC) have been shown to inhibit tumor growth in different studies. Although MSC express MHC class I molecules, which lack expression of costimulatory molecules and suppress T cell response, which gives the utility to overcome a wide range of immunological barriers. Furthermore, the ability of MSC to home in on sites of tumor growth is well known as plasticity allows them to differentiate into bone, cartilage, fat, muscle, neurons and other tissues. Systemic administration of MSC in mice has been shown to engraft in the tumor microenvironment in many types of cancer and therefore represents an attractive vehicle for gene therapy strategies cell .
In a preclinical mouse model, we have recently shown that the application of unmodified MSC, constitutively expressing (OPG) in inhibiting the growth of prostate tumors in bone formation by new bone and loss prevention bone. Although this treatment has shown promise in the early stages of bone metastasis, it is irrelevant when tested against established prostate tumors in bone. This limitation is because the number of MSC that could be injected into mice of the tibia, an excess of 5x105 cells routinely results in a certain degree of pulmonary embolism. In this scenario, the number of cancer cells in established tumors outnumbered the MSC, resulting in modest therapeutic effects. Apart from
therapeutic benefits of MSC OPG expression in the early stages of bone metastasis, this study also indicates the presentation of bone tissue in bone metastases prostate cancer. In our study, the therapeutic effect of MSC is given initially in the formation of spongy bone around the tumor nests. The spongy bone formation is normal fracture healing and osteoblastic metastases characteristic in Prostate cancer, unlike other types of metastatic bone cancer are primarily osteolytic nature. Based on our observations, we hypothesized that the spongy bone formation of bone metastases in prostate cancer is an endogenous therapeutic response given by the resident MSC. Roudier and colleagues (2008) studied bone samples from patients with prostate cancer and bone metastases showed the spongy bone formation in osteoblastic metastases originate in the skeletal MSC, which also supports our results. When we compare the growth kinetics of large osteolytic PC3 human prostate cancer osteoblastic cell line C4-2B cell line in the tibia of mice, aggressive PC3 cells proliferated and led to severe bone loss within a month, while the C4-2B cells grew to a significantly slower rate, initially generated an osteoblastic phenotype, but in the long run turned to an osteolytic phenotype. We believe that the slow progression of C4-2B cells provides a therapeutic window for endogenous MSC to restore bone loss caused by the initial osteolytic phenomenon required for Ca ; cancer to establish the growth in the bone microenvironment. This observation must be confirmed in human patients with bone metastases prostate.
Our cooperation in the in vitro testing indicate MSC has no negative effect on the proliferation of cell line PC3 prostate cancer. In our animal model, MSC limited the treatment of tumor growth in bone, but not completely remove the tumor. Metastatic tumors Therefore, the therapeutic application of MSC alone may not be sufficient for the eradication of the bones. MSC express tumoricidal Ex vivo gene engineering as well as maintaining self-renewal and differentiation of the properties will be useful as combination therapy. MSC treatment can also be applied as adjuvant therapy in addition to chemotherapy or radiotherapy to restore lost bone mass and prevent cancer, the promotion of mechanisms such as angiogenesis.
This study was based on a tumor located in the tibia of ratóny not accurately represent bone metastases in prostate cancer has become widespread in esqueleto. Por lo tanto, el concepto propuesto debe ser puesta a prueba en un total de metástasis ósea del cuerpo, en un modelo animal preclínicos, antes de la traducción clínica en seres humanos.
Escrito por Diptiman Chanda, PhD, y Selvarangan Ponnazhagan, PhD, como parte de Más allá del resumen en UroToday.com. Esta iniciativa ofrece un método de publicación para la comunidad profesional de la urología. Los autores se les da la oportunidad de ampliar las circunstancias, limitaciones, etc, de sus investigaciones con referencia a la publicación abstracto.
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