Oral Mucosal Lamina Propria-Progenitor Cells Exert Antibacterial Properties via the Secretion of Osteoprotegerin and Haptoglobin

Abstract

The oral cavity possesses a diverse microflora, yet recurrent infections within healthy individuals are rare. Wound healing within the buccal mucosa is preferential, potentially because of the presence of oral mucosal lamina propria-progenitor cells (OMLP-PCs). In addition to their multipotency, OMLPPCs demonstrate potent immunosuppressive properties. The present study investigated whether OMLP-PCs possess antibacterial properties, directly interacting with microorganisms and contributing to the maintenance of a balanced oral microflora. Gram-positive and -negative bacteria were cocultured with OMLP-PCs, buccal mucosal fibroblasts, or their respective conditioned media (CM). Bacterial growth was significantly inhibited when cocultured with OMLP-PCs or their CM. No antibacterial activity was apparent within the fibroblasts. Analysis of the OMLP-PC CM indicated constitutive secretion of osteoprotegerin (OPG) and haptoglobin (Hp). Exposure of the bacteria to OPG or Hp demonstrated their differential antibacterial properties, with neutralization/blocking studies confirming that the growth of Gram-positive bacteria was partially restored by neutralizing OPG within OMLP-PC CM; blocking Hp restored the growth of Gram-negative bacteria. The present study demonstrates, for the first time, the broad-spectrum antibacterial properties of OMLP-PCs. We report the direct and constitutive antibacterial nature of OMLP-PCs, with retention of this effect within the CM suggesting a role for soluble factors such as OPG and Hp. Knowledge of the immunomodulatory and antibacterial properties of these cells could potentially be exploited in the development of novel cell-or soluble factor-based therapeutics for the treatment of infectious diseases such as pneumonia or ailments such as chronic nonhealing wounds. STEM CELLS TRANSLATIONAL MEDICINE 2015; 4:1283-1293 SIGNIFICANCEOral mucosal lamina propria-progenitor cells (OMLP-PCs) are a cell source with known immunomodulatory properties. The present report demonstrates the novel finding that OMLP-PCs possess potent antibacterial properties, halting the growth of Gram-positive and -negative bacteria through the secretion of soluble factors. OMLP-PCs constitutively secrete osteoprotegerin (OPG) and haptoglobin (Hp) at levels high enough to exert antibacterial action. OPG, a glycoprotein not previously known to be antibacterial, can suppress Gram-positive bacterial growth. Hp is only active against Gramnegative microorganisms. These findings indicate that OMLP-PCs could offer great potential in the development of novel cell-or soluble factor-based therapies for the treatment of infectious illness, such as bacterial pneumonia, through systemic infusion and of chronic wounds through local administration.

Three‐dimensional culture of oral progenitor cells: Effects on small extracellular vesicles production and proliferative function

“…9 OMLP-PCs are also multipotent, 10 immunosuppressive, 11 and anti-bacterial. 12 In recent years, it has been reported that paracrine factors derived from stem cells are the main facilitators in driving tissue repair.…”

Oral cavity-derived exosomes as promising tool in chronic wound healing

“…Physiologically, this region is constantly exposed to injury, however renewal and healing are very prompt. Oral cavity is easily accessible and displays unique characteristics such as fetal-like wound healing [26] and antibacterial properties [27,28]. The oral cavity has antibacterial properties as a part of the native immunity.…”

“…Epithelial antimicrobial peptides (β-defensin coming from oral epithelium) have been identified and examined [29]. Also osteoprotegerin and haptoglobin -peptides secreted by progenitor cells of lamina propria, reduce growth of several pathogens [27]. It is easy to notice that wounds appearing in this region are healed much faster than those affecting skin, carrying low risk of scars formation.…”

Exosomes derived from clinical‐grade oral mucosal epithelial cell sheets promote wound healing

“…The oral mucosa is a suitable cell source for tissue engineering and regenerative medicine applications, including cell sheet fabrication. It is easily accessible and exhibits unique characteristics such as foetal‐like wound healing [1] and antibacterial properties [2,3]. While skin wounds generally heal with scar (“reparation”), wounds in the oral mucosa are prone to heal without scar (“regeneration”) [4].…”

“…These peptides operate by disrupting the microbe cell membrane [17]. Progenitor cells from the oral mucosal lamina propria similarly secrete the antimicrobial peptides osteoprogetrin and haptoglobin, which, in effect, could reduce the growth of several pathogens [2]. To this end, we evaluated the exosomes impact on growth of Staphylococcus aureus .…”