The therapeutic potential of dental pulp cells: more than pulp fiction?

Abstract

In this issue of Cytotherapy , two papers highlight dental pulp as an important source of mesenchymal stromal cells (MSC) for potential application as cell therapy for autoimmune and related disorders. Multipotential dental pulp stem cells (DPSC) in adult human dental pulp tissue can regenerate a dentine – pulp complex in vivo and exhibit immunomodulatory properties similar to those described for bone marrow-derived MSC (BMSC) (1,2). In this issue, Demircan et al. (3) describe the immunoregulatory effects of human DPSC on T-cell subsets. They confi rm a previous report demonstrating that ex vivo -expanded DPSC suppress T-cell responses following co-culture with phytohemagglutinin-stimulated allogeneic T cells in vitro (4). Subsequent comparative studies have shown that human DPSC inhibit allogeneic mixed lymphocyte reactions and mitogen-stimulated lymphocytes when co-cultured with either BMSC or periodontal ligament stem cells (PDLSC) (2). Moreover, DPSC, BMSC and PDLSC expressed comparable gene expression levels of candidate inhibitory molecules, such as transforming growth factor (TGF)β 1, hepatocyte growth factor (HGF) and indoleamine 2,3-dioxygenase (IDO) up-regulated following coculture with activated lymphocytes or stimulation with interferon (IFN)γ . Similarly, co-cultures performed by Demircan et al. (3) showed that activated T cells stimulated DPSC to increase expression of human leukocyte antigen (HLA)-G, HGFβ 1, intracellular adhesion molecule (ICAM)-1, IDO, interleukin (IL)-6, IL-10, prostaglandin E 2 (PGE 2 ), TGFβ and vascular adhesion molecule (VCAM)-1, previously shown to mediate MSC suppression of Tcell proliferation. Furthermore, interactions between DPSC and mitogen-stimulated T cells decreased the expression of pro-infl ammatory cytokines IFNγ , IL-2, IL-6R, IL-12, IL-17A and tumor necrosis factor (TNF)α and increased expression of the anti-infl ammatory cytokine IP-10. Interestingly, CD4 CD25 Foxp3 and Treg (regulatory T-cells) cells increased when co-cultured with DPSC. This observation confi rms the ability of MSC-like populations to suppress immune and infl ammatory responses via multiple mechanisms, supporting the notion of using allogeneic DPSC preparations to treat immune-related conditions. While the immunomodulatory potential of MSClike populations derived from different tissues holds great appeal for the treatment of autoimmune and infl ammatory diseases, it must be stressed that this is not a unique property of MSC-like cells. We and others have reported that non-multipotent fi broblasts derived from various tissues exhibit comparable capacities to suppress immune responses and express many MSC-associated markers, including CD29, CD44, CD73, CD90, CD105 and CD166, while lacking expression of immune helper antigens such as HLD-DR, CD40, CD80 and CD86 (2,4,5). However, different fi broblast populations may utilize alternative mechanisms of action and could modulate varying effects on specifi c subsets of immune cells. The challenge is identifying whether specifi c MSC-like or fi broblast populations are more effi cacious for particular clinical indications using appropriate pre-clinical models, and ultimately identifying the precise mechanisms involved in these processes for each disease state. In the second paper on dental pulp cells, Bhonde et al . (6) describes the use of human platelet lysate (HPL) as a media growth supplement for the clinical scale-up of ex vivo -expanded DPSC. Most preclinical and clinical trials utilizing ex vivoexpanded (MSC)-like populations currently use fetal bovine serum (FBS). While certain batches of FBS have been approved by regulatory bodies for the manufacture of clinical-grade MSC, serum-free media may be required in the future for good manufacturing Cytotherapy, 2011; 13: 1162–1163