Monocytes induce survival and activation of Mesenchymal Stem Cells

Monocytes induce survival and activation of Mesenchymal Stem Cells

The Jane and Jerry Weintraub center for reconstructive biotechnology, The Jonsson Comprehensive Cancer Center, Dental Research Institute and the Division of Oral Biology and Oral Medicine. UCLA School of Dentistry, Los Angeles, CA 90095.

Objective: Mesenchymal stem cells (MSCs) are much more sensitive to death inducing agents than their differentiated counterpart, osteoblasts. In this study we identified the subset of immune effectors with the ability to aid in survival and expansion of MSCs.

Methods: Mesenchymal stem cells were co-cultured with peripheral blood mononuclear cells, peripheral blood lymphocytes, monocytes and natural killer cells, and the levels of alkaline phosphatase staining and VEGF secretion were determined. The level of NFkB induction by each of the subsets indicated above was also determined and correlated with the sensitivity and resistance of the MSCs.

Results: Naïve but not IL-2 activated peripheral blood mononuclear cells (PBMCs) induce survival and differentiation of Mesenchymal Stem Cells (MSCs). Monocytes, but not lymphocytes, were found to induce survival and functional activation of MSCs, and protected these cells from NK cell mediated cytotoxicity. Monocytes induced protection and survival of the cells by increased induction of NFkB. Indeed, monocytes were the only cell population within the peripheral blood with the ability to induce high levels of NFkB and stimulate the release of VEGF in addition to increasing alkaline phosphatase staining of MSCs.

Conclusions: Monocytes are protective for the survival and functional activation of MSCs. Therefore, to protect and expand the population of MSCs, they can be cultured in the presence of monocytes for tissue engineering purposes.

This study was supported by institutional funding.