Hematopoietic Stem Cells as a Novel Source of Dental Tissue Cells

Wilson, Katie R.; Kang, In-Hong; Baliga, Uday; Xiong, Ying; Chatterjee, Shilpak; Moore, Emily; Parthiban, Beneta; Thyagarajan, Krishnamurthy; Borke, James L.; Mehrotra, Shikhar; Kirkwood, Keith L.; LaRue, Amanda C.; Ogawa, Makio; Mehrotra, Meenal

doi:10.1038/s41598-018-26258-y

Cited by 10 publications

(10 citation statements)

References 47 publications

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“…In addition, MSCs are not the only source of osteogenic cells. Several previous studies reported other possible cell sources that could be converted to osteogenic cells, for example, endothelial cells [ 6 ], endoneurial progenitor cells [ 7 ], and hematopoietic stem cells [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Pericytes as a Source of Osteogenic Cells in Bone Fracture Healing

Supakul

Yao

Ochi

et al. 2019

IJMS

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Pericytes are mesenchymal cells that surround the endothelial cells of small vessels in various organs. These cells express several markers, such as NG2, CD146, and PDGFRβ, and play an important role in the stabilization and maturation of blood vessels. It was also recently revealed that like mesenchymal stem cells (MSCs), pericytes possess multilineage differentiation capacity, especially myogenic, adipogenic, and fibrogenic differentiation capacities. Although some previous studies have reported that pericytes also have osteogenic potential, the osteogenesis of pericytes can still be further elucidated. In the present study, we established novel methods for isolating and culturing primary murine pericytes. An immortalized pericyte line was also established. Multilineage induction of the pericyte line induced osteogenesis, adipogenesis, and chondrogenesis of the cells in vitro. In addition, pericytes that were injected into the fracture site of a bone fracture mouse model contributed to callus formation. Furthermore, in vivo pericyte-lineage-tracing studies demonstrated that endogenous pericytes also differentiate into osteoblasts and osteocytes and contribute to bone fracture healing as a cellular source of osteogenic cells. Pericytes can be a promising therapeutic candidate for treating bone fractures with a delayed union or nonunion as well as bone diseases causing bone defects.

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Section: Introductionmentioning

confidence: 99%

Pericytes as a Source of Osteogenic Cells in Bone Fracture Healing

Supakul

Yao

Ochi

et al. 2019

IJMS

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“…Some studies have suggested that monocyte/macrophage progenitors differentiate into adipocytes [23]; however, most studies did not identify the type of hematopoietic cells that can differentiate directly into cells of other lineages. Mehrotra et al also reported that HSCs can differentiate into cells in pulp and 6-24% hematopoietic-derived cells were detected when cultured pulp cells were analyzed [10]. However, this indicates that a smaller number of hematopoietic-derived cells was present before culture and that the number of hematopoietic cells could also have been smaller.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies using human teeth have shown that dental pulp contains few hematopoietic stem and progenitor cells (HSPCs) that supply immune cells [ 9 ]. However, it has also been reported that cells derived from hematopoietic stem cells (HSCs) are present in the dental pulp, periodontal ligament, and alveolar bone, and that hematopoietic cells differentiate into dental tissue cells [ 10 ]. This raises a new possibility for the existence of HSPCs in dental pulp.…”

Section: Introductionmentioning

confidence: 99%

Hematopoietic progenitor cells specifically induce a unique immune response in dental pulp under conditions of systemic inflammation

Osaki

Yamazaki

Hikita

et al. 2022

Heliyon

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Teeth are exposed to various stimuli, including bacterial, thermal, and physical stimuli. Therefore, immune cells present in the normal dental pulp and the immune response to these stimuli have been studied. However, the relationship between systemic inflammation, such as that induced by viral infection, and changes occurring in dental pulp is not well known. This study aimed to investigate the immunological and hematological responses to systemic inflammation in dental pulp. Poly(I:C), a toll-like receptor 3 agonist, was injected into mice every two days to simulate a systemic inflammatory state in which type I interferon (IFN-I) was produced. The untreated normal state was defined as a steady state, and the states of acute and chronic inflammation were defined according to the period of administration. Changes in the abundance and dynamics of hematopoietic and immune cells in dental pulp, bone marrow and peripheral blood were quantitatively investigated in the steady state and under conditions of inflammation induced by IFN-l. We found that dental pulp in the steady state contained only a few hematopoietic cells, but a greater variety of immune cells than previously reported. B cells were also found in the steady state. An increase in multipotent progenitor cell levels was observed in the dental pulp during both acute and chronic inflammation. The increased multipotent progenitor cells in the dental pulp during acute inflammation tended to differentiate into the myeloid lineage. On the other hand, there was an influx of B cells into the dental pulp during chronic inflammation. These results revealed that a unique immune response is induced in the dental pulp by systemic inflammation, which would lead to a significant change in the perspective of dentists on the utility of dental pulp in the management of systemic diseases.

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“…These included 1) scleraxis, a transcription factor expressed in tendon progenitor populations and mature tendon and which has also been found in PDL fibroblasts (30)(31)(32)(33) and 2) neurofilament, a structural protein of mature nerve fibers, was seen in the pulp and also found in the PDL (34). The known pulp markers of progenitor cell populations, shown to be mesenchymal stem cells (MSC), alpha smooth muscle actin (aSMA) and CD44 (35)(36)(37)(38), were increased after drug treatment. Furthermore, the possibility of tissue de-differentiation followed by re-differentiation into mature tissue, a hallmark of classic epimorphic regeneration with .…”

Section: Introductionmentioning

confidence: 94%

“…Stem cell populations have been identified that are associated with teeth in the pulp chamber, at the base of growing roots, and in the PDL (59). Progenitor cell populations have been identified in periodontal tissue previously and express mesenchymal stem cell markers such as STRO-1, CD146, CD44, and αSMA (30)(31)(32)(33)(60)(61)(62).…”

Section: Induction Of Stem Cell Markersmentioning

confidence: 99%

Prolyl-hydroxylase inhibitor-induced regeneration of alveolar bone and soft tissue in a mouse model of ligature-induced periodontitis

Zebrowitz

Kajikawa

Bedelbaeva

et al. 2021

Preprint

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Bone injuries and fractures reliably heal through a process of regeneration with restoration to original structure and function when the gap between adjacent sides of a fracture site is small. However, when there is significant volumetric loss of bone, bone regeneration usually does not occur.In the present studies, we explore a particular case of volumetric bone loss in a mouse model of human periodontal disease (PD) in which alveolar bone surrounding teeth is permanently lost and not replaced. This model employs the placement a ligature around the upper second molar which leads to inflammation and bone breakdown and faithfully replicates the bacterially-induced inflammatory etiology of human PD to induce bone degeneration. After 10 days, the ligature is removed and the mice are treated with a timed-release formulation of a small molecule inhibitor of prolylhydroxylases (PHDi; 1,4-DPCA) previously shown to induce epimorphic regeneration of soft tissue in non-regenerating mice. This PHDi induces high expression of HIF-1α and the regenerative response is completely blocked by siHIF1a. Here, we observe that timed-release 1,4-DPCA rapidly and completely restores bone and soft tissue with normal anatomic fidelity and with increased stem cell markers due to stem cell migration into the site and/or de-differentiation of local tissue, PDL cell proliferation, and increased vascularization. In-vitro studies using gingival tissue show that 1,4-DPCA indeed induces de-differentiation and the expression of stem cell markers but does not exclude the role of migrating stem cells.

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Hematopoietic Stem Cells as a Novel Source of Dental Tissue Cells

Cited by 10 publications

References 47 publications

Pericytes as a Source of Osteogenic Cells in Bone Fracture Healing

Pericytes as a Source of Osteogenic Cells in Bone Fracture Healing

Hematopoietic progenitor cells specifically induce a unique immune response in dental pulp under conditions of systemic inflammation

Prolyl-hydroxylase inhibitor-induced regeneration of alveolar bone and soft tissue in a mouse model of ligature-induced periodontitis

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