Stem cell-based bone and dental regeneration: a view of microenvironmental modulation

Abstract

In modern medicine, bone and dental loss and defects are common and widespread morbidities, for which regenerative therapy has shown great promise. Mesenchymal stem cells, obtained from various sources and playing an essential role in organ development and postnatal repair, have exhibited enormous potential for regenerating bone and dental tissue. Currently, mesenchymal stem cells (MSCs)-based bone and dental regeneration mainly includes two strategies: the rescue or mobilization of endogenous MSCs and the application of exogenous MSCs in cytotherapy or tissue engineering. Nevertheless, the efficacy of MSC-based regeneration is not always fulfilled, especially in diseased microenvironments. Specifically, the diseased microenvironment not only impairs the regenerative potential of resident MSCs but also controls the therapeutic efficacy of exogenous MSCs, both as donors and recipients. Accordingly, approaches targeting a diseased microenvironment have been established, including improving the diseased niche to restore endogenous MSCs, enhancing MSC resistance to a diseased microenvironment and renormalizing the microenvironment to guarantee MSC-mediated therapies. Moreover, the application of extracellular vesicles (EVs) as cell-free therapy has emerged as a promising therapeutic strategy. In this review, we summarize current knowledge regarding the tactics of MSC-based bone and dental regeneration and the decisive role of the microenvironment, emphasizing the therapeutic potential of microenvironment-targeting strategies in bone and dental regenerative medicine.

The Few Who Made It: Commercially and Clinically Successful Innovative Bone Grafts

“…Cell source in bone tissue engineering is a matter of debate, where the type of stem cell chosen for in vitro and in vivo experimentation notably differs in the literature ( Gao et al, 2017 ). Bone marrow stromal cells (BMSCs), however, have been the preferred choice in clinical studies due to their intimate involvement in bone physiology and pathology, osteogenic potency, and anti-inflammatory properties ( Zheng et al, 2019 ). Cell therapy for bone regeneration using freshly extracted BMSCs is a technique with 30 years of history.…”

Fabrication of Dentin-Pulp-Like Organoids Using Dental-Pulp Stem Cells

“…Regenerative approaches using biological materials offer a promising strategy to achieve dental structure repair [8]. In tooth or tooth-supporting tissues, various types of stem cells have been identified, including dental-pulp stem cells (DPSCs) [9], periodontal ligament stem cells [10], stem cells from apical papilla [11], and dental follicle cells [12]. Among these, DPSCs of mesenchymal cell lineages that reside in the pulp hold great potential for proliferation.…”

A comparative study on immunophenotypic characterization and osteogenic differentiation of human mesenchymal stromal cells derived from periodontal ligament and gingiva

“…9,11 The gingiva, which is are easily obtainable by dentists, seems to be a promising source of adult stem cells. [12][13][14] According to International Society for Cellular Therapy (ISCT), there are three criteria for mesenchymal stromal cells: (1) Adherence of MSCs to cell culture plate, (2) Expression of some cluster differentiation (CD) markers such as CD73, CD90, CD105, and (3) Differentiation into adipocytes, osteoblasts, and chondroblasts in vitro. 15 Gingival tissues and teeth are suitable sources for stem cells because they are commonly extracted and discarded as waste.…”