Investigation of orofacial stem cell niches and their innervation through microfluidic devices

Abstract

Stem cell-based mediated therapies represent very promising approaches for tissue regeneration and are already applied with success in clinics. These therapeutic approaches consist of the in vitro manipulation of stem cells and their consequent administration to patients as living and dynamic biological agents. Nevertheless, the deregulation of stem cells function might result in the generation of pathologies such as tumours or accelerated senescence. Moreover, different stem cells sources are needed for regeneration of specific tissues. It is thus fundamental to understand the mechanisms regulating the physiology of stem cells. Microfluidic technology can be used to mimic in vivo scenarios and allow the study of stem cell physiology at both single cell and whole stem cell niche levels. This review focuses on the potential sources of stem and progenitor cells for orofacial regeneration and the use of microfluidic technologies for the study of stem cells behaviour and stem cell niches, in the light of regenerative medicine. Keywords:Microfluidics, stem cells, stem cell niches, orofacial regeneration, tooth, innervation, trigeminal ganglia, regenerative medicine. IntroductionThe development of organs and tissues that belong to the orofacial complex proceeds through a series of inductive interactions between cells originated from the epithelium, mesoderm and cranial neural crest-derived mesenchyme (Mao et al., 2012;Mitsiadis and Graf, 2009;Mitsiadis and Papagerakis, 2011). Orofacial organs are highly diverse and exert fundamental and specific functions such as breathing, chewing, speech, smell, and sight (Mao et al., 2012). The physiological functions of these organs are compromised by traumatic injuries, congenital and infectious diseases, and cancer (Mao et al., 2012;Scheller et al., 2009). Furthermore, these pathologies are often accompanied by intensive pain and aesthetic deformities. Therefore, the treatment of compromised pathological orofacial tissues and organs should guarantee restoration of both functionality and aesthetics, which constitutes an enormous clinical challenge. Moreover, organ structure, function, aesthetics, and pain should be managed simultaneously during the regenerative care, a situation that is more complex than in other compartments of the body (Scheller et al., 2009).Biological regeneration is proving an increasingly attractive alternative and complement to traditional surgical techniques for prosthetic replacement of tissues and organs. Cell-based therapeutic approaches are already applied with success in clinics and consist of in vitro manipulation of stem cells and their consequent administration to patients as living and dynamic biological agents. Stem cells are characterised by their potential to self-replicate and their capacity to differentiate into a vast variety of cell types that form the diverse tissues. Therefore, stem cells guarantee tissue repair and regeneration throughout life. During the last decades, a plethora of adult stem cell populations have been isolate...

Stem cell-based approaches in dentistry

“…Cultures of DMSCs and MSCs are indistinguishable, and at present no markers permit selective identification of either cell type from culture-expanded DMSC populations (Pagella et al, 2015). Likewise, it is not yet known whether DMSC properties reside in distinct cell subpopulations.…”

“…Despite similar phenotypic characteristics, DMSCs from different locations have significant functional heterogeneity both in vitro and in vivo, thus indicating distinct physiological roles within teeth Pagella et al, 2015). In the dental pulp, DMSCs are located mainly in two niches: the apical niche and the perivascular niche Zhao et al, 2014).…”

“…Indeed, MSCs are found in the circulation and are likely to engraft in all tissues of the body (Kuroda et al, 2014;Lemoli et al, 2006). The embryonic origins of circulating MSCs are different from those of DMSCs (La Noce et al, 2014;Pagella et al, 2015), thus suggesting distinct properties and functions for these two stem cell populations. The various dental stem cell populations and their potencies are described in Fig.…”

Immunophenotyping Reveals the Diversity of Human Dental Pulp Mesenchymal Stromal Cells In vivo and Their Evolution upon In vitro Amplification

“…In particular, studies have demonstrated that mesenchymal stromal/stem cells (MSCs) are suitable to these protocols because of their high expansion ability and differentiation potential both in culture and animal models. MSC-based therapies have already been applied in the clinics and mainly consist of administration of cells, alone, or together with scaffolds, to damaged, or pathological sites (Pagella et al, 2015). Bone marrow (BM), Wharton's jelly and adipose tissue are conventional sources of MSCs, but owing to the easy tooth access and the low morbidity of tooth collection protocols, dental pulp (DP) previously emerged as an valuable source of MSCs for tissue engineering-based therapies (Huang et al, 2009; Harrington et al, 2014).…”

“…Pioneering studies of Gronthos et al (2000) demonstrated that undifferentiated DP cells include a small population—less than 5% of cells—that possess phenotypic features of MSCs and are able to form a pulp-dentin complex upon engraftment in vivo in immunodeficient mice (Gronthos et al, 2000). DP-MSCs mostly reside in perivascular stem cell niches that provide cells a highly regulated microenvironment instructing them to remain quiescent and preventing them to proliferate, differentiate, or undergo apoptosis (Moore and Lemischka, 2006; Mitsiadis et al, 2007; Pagella et al, 2015). Perivascular localization of DP-MSCs was ascertained by the fact that a large proportion (more than 60%) of clonogenic DP-MSCs were present in the pericyte fraction and by their expression of specific pericyte and smooth muscle cell markers (Shi and Gronthos, 2003; Alliot-Licht et al, 2005; Lopez-Cazaux et al, 2006).…”