The novel-molecule T11TS facilitated arousal of glioma-mediated dormancy of bone-marrow hematopoietic stem-cells

Aim: T11TS, a potent anti-gliomagenic glycoprotein, stimulates both peripheral and intracranial immune response. The status of bone marrow hematopoietic stem cells (BMHSCs), the cradle of regeneration of all blood cells, during gliomagenic global immune devastations has not yet been investigated. Therefore, we aimed to delineate the effects of T11TS on immature and mature compartments of hematopoietic machinery. Methods: Flowcytometric analysis of cultured BMHSCs was evaluated for assesing the expression pattern of early hematopoietic stem cells (HSCs) markers such as CD34, Sca-1, c-kit and also Angiopoietin-1 and Tie-2 both in normal, glioma, and in T11TS treated glioma-bearing animals. Immunofluresenece imaging and western blot analyses of BMHSCs were also carried out. Results: There was significant downregulation of HSCs-markers CD34, Sca-1, c-kit in ethyl nitrosourea-induced gliomabearing animals followed by an increase in the expression level of Ang-1 and Tie-2 that determines the quiescence and self-renewability of stem cells. T11TS administration reversed the gliomagenic transformation of expression of the above mentioned markers. The results flowcytometric-analysis was also well corroborated with immunofluorescence imaging and western blot analysis. Conclusion: Collectively, the above experimental evidence hints towards gliomagenic maneuver of receptor expression of HSCs to derange the systemic immunity and T11TS mediated manipulation towards revival/rejuvenation of the same.