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Background Mesenchymal stem cells (MSC) are used for several therapeutic applications to improve the functions of bone, cardiac, nervous tissue as well as to facilitate the repopulation of hematopoietic stem cells. MSC give rise to the non-hematopoietic stromal cells of the bone marrow and are important for the maintenance of normal hematopoiesis. Chemotherapeutic drugs used for treatment of leukemia extensively damage the stromal cells and alter their gene expression profiles. Methods We determined the changes in adipogenic, osteogenic differentiation, phenotypic and gene expression in MSC during treatment with chemotherapeutic drugs cytarabine, daunorubicin and vincristine. We also tested anti-cancer effects of drug treated MSC on leukemia cells. Results Treatment with the chemotherapeutic drugs resulted in functional defects in MSC, leading to reduced proliferation, osteogenic and adipogenic differentiation. The drug treated MSC also showed decreased expression of cell surface receptors, and the changes in proliferation, phenotype and differentiation defect was partially reversible after withdrawing the drugs from the cells. The drug treated MSC showed increased expression of cytokines, IL6, FGF2 and TNFA but reduced levels of differentiation markers SOX9 and ACTC1. Drug treated MSC also contributed to reduced anti-cancer effects in leukemia cells. Conclusions Chemotherapeutic drug treatment altered the phenotype, osteogenic and adipogenic differentiation potential of MSC and modified the gene expression profile of the cells to render them more chemoprotective of the leukemic cells. Thus, additional therapeutic efforts to target the stromal cell population will help in preventing chemoresistance, disease relapse in leukemia and to maintain a healthy bone marrow stroma. Electronic supplementary material The online version of this article (10.1186/s12929-018-0407-7) contains supplementary material, which is available to authorized users.

Dose response curve and chemoprotection of leukemia cells by MSC. a-c Dose response curve showing percentage of live cells after treatment with indicated concentrations of CYT, DAU and VIN after 48 h. d THP1 leukemia cells were cultured for 48 h in the absence of MSC (CON) or in the presence of MSC (+MSC) or in the presence of drug pre-treated MSC (+PRE-TR MSC). The cells were treated with CYT (10mM), DAU (0.1mM) for 48 h and apoptosis percentage was analyzed flow cytometrically. Values are mean+SD, n=3 samples. *p

Dose response curve and chemoprotection of leukemia cells by MSC. a-c Dose response curve showing percentage of live cells after treatment with indicated concentrations of CYT, DAU and VIN after 48 h. d THP1 leukemia cells were cultured for 48 h in the absence of MSC (CON) or in the presence of MSC (+MSC) or in the presence of drug pre-treated MSC (+PRE-TR MSC). The cells were treated with CYT (10mM), DAU (0.1mM) for 48 h and apoptosis percentage was analyzed flow cytometrically. Values are mean+SD, n=3 samples. *p

Dose response curve and chemoprotection of leukemia cells by MSC. a-c Dose response curve showing percentage of live cells after treatment with indicated concentrations of CYT, DAU and VIN after 48 h. d THP1 leukemia cells were cultured for 48 h in the absence of MSC (CON) or in the presence of MSC (+MSC) or in the presence of drug pre-treated MSC (+PRE-TR MSC). The cells were treated with CYT (10mM), DAU (0.1mM) for 48 h and apoptosis percentage was analyzed flow cytometrically. Values are mean+SD, n=3 samples. *p

Mesenchymal stem cells (MSC) can differentiate into several cell types and are desirable candidates for cell therapy and tissue engineering. However, due to poor cell survival, proliferation and differentiation in the patient, the therapy outcomes have not been satisfactory. Although several studies have been done to understand the conditions that promote proliferation, differentiation and migration of MSC in vitro and in vivo, still there is no clear understanding on the effect of non-cellular bio molecules. Of the many factors that influence the cell behavior, the immediate cell microenvironment plays a major role. In this context, we studied the effect of extracellular matrix (ECM) proteins in controlling cell survival, proliferation, migration and directed MSC differentiation. We found that collagen promoted cell proliferation, cell survival under stress and promoted high cell adhesion to the cell culture surface. Increased osteogenic differentiation accompanied by high active RHOA (Ras homology gene family member A) levels was exhibited by MSC cultured on collagen. In conclusion, our study shows that collagen will be a suitable matrix for large scale production of MSC with high survival rate and to obtain high osteogenic differentiation for therapy.