Characterization of the Apical Papilla and Its Residing Stem Cells from Human Immature Permanent Teeth: A Pilot Study

Recent advances in understanding the cellular and molecular signaling pathways and global transcriptional regulators of adult mesenchymal stem cells have provided new insights into their biology and potential clinical applications, particularly for tissue repair and regeneration. This review focuses on these advances, specifically in the context of self-renewal and regulation of lineage-specific differentiation of mesenchymal stem cells. In addition we review recent research on the concept of stem cell niche, and its relevance to adult mesenchymal stem cells.

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Mesenchymal stromal cells. Biology of adult mesenchymal stem cells: regulation of niche, self-renewal and differentiation

The potential use of stem cell-based therapies for the repair and regeneration of various tissues and organs offers a paradigm shift that may provide alternative therapeutic solutions for a number of diseases. The use of either embryonic stem cells (ESCs) or induced pluripotent stem cells in clinical situations is limited due to cell regulations and to technical and ethical considerations involved in the genetic manipulation of human ESCs, even though these cells are, theoretically, highly beneficial. Mesenchymal stem cells seem to be an ideal population of stem cells for practical regenerative medicine, because they are not subjected to the same restrictions. In particular, large number of adipose-derived stem cells (ASCs) can be easily harvested from adipose tissue. Furthermore, recent basic research and preclinical studies have revealed that the use of ASCs in regenerative medicine is not limited to mesodermal tissue but extends to both ectodermal and endodermal tissues and organs, although ASCs originate from mesodermal lineages. Based on this background knowledge, the primary purpose of this concise review is to summarize and describe the underlying biology of ASCs and their proliferation and differentiation capacities, together with current preclinical and clinical data from a variety of medical fields regarding the use of ASCs in regenerative medicine. In addition, future directions for ASCs in terms of cell-based therapies and regenerative medicine are discussed. STEM CELLS 2012;30:804–810

https://stemcellsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/stem.1076

Concise Review: Adipose‐Derived Stem Cells as a Novel Tool for Future Regenerative Medicine

PDGF, TGF-beta, and FGF signaling is important for differentiation and growth of mesenchymal stem cells (MSCs): transcriptional profiling can identify markers and signaling pathways important in differentiation of MSCs into adipogenic, chondrogenic, and osteogenic lineages.

Mesenchymal Stem Cells

Adult human mesenchymal stem cells (hMSCs) possess multilineage differentiation potential, and differentiated hMSCs have recently been shown to have the ability to transdifferentiate into other lineages. However, the molecular signature of hMSCs is not well-known, and the mechanisms regulating their self-renewal, differentiation, and transdifferentiation are not completely understood. In this study, we demonstrate that fully differentiated hMSCs could dedifferentiate, a likely critical step for transdifferentiation. By comparing the global gene expression profiles of undifferentiated, differentiated, and dedifferentiation cells in three mesenchymal lineages (osteogenesis, chondrogenesis, and adipogenesis), we identified a number of "stemness" and "differentiation" genes that might be essential to maintain adult stem cell multipotency as well as to drive lineage-specific commitment. These genes include those that encode cell surface molecules, as well as components of signaling pathways. These genes may be valuable for developing methods to isolate, enrich, and purify homogeneous population of hMSCs and/or maintain and propagate hMSCs as well as guide or regulate their differentiation for gene and cell-based therapy. Using small interfering RNA gene inactivation, we demonstrate that five genes (actin filament-associated protein, frizzled 7, dickkopf 3, protein tyrosine phosphatase receptor F, and RAB3B) promote cell survival without altering cell proliferation, as well as exhibiting different effects on the commitment of hMSCs into multiple mesenchymal lineages.

Identification and functional analysis of candidate genes regulating mesenchymal stem cell self-renewal and multipotency.

Much of the knowledge regarding the regulatory pathways for adult stem cell self-renewal and differentiation has been obtained from the results of in vitro cultures. However, it is unclear if adult stem cells are controlled in the same way under physiological conditions. We examined this issue with respect to the migration of stem cells to tissue injury and how switch from a migratory state to one of proliferation wherein they participate in development. Building on our previous identification of multipotent stem cells in trabecular bone, we have examined the in vitro behavior of these cells within the bone milieu. We found that cell proliferation is inhibited within the trabecular bone niche as cells migrate out of the trabecular bone prior to proliferation. Additionally, multiple cell types were detected in adult trabecular bone, including osteoblasts, osteoclasts, endothelial cells, and Stro-1-positive mesenchymal stem cells. Furthermore, we demonstrated that Stro-1-positive cells migrated out of their...

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Nicole E. Webb

Papers

Identification and functional analysis of candidate genes regulating mesenchymal stem cell self-renewal and multipotency.

Origin and characterization of multipotential mesenchymal stem cells derived from adult human trabecular bone.