scholarly journals Dental Pulp Stem Cell Heterogeneity: Finding Superior Quality “Needles” in a Dental Pulpal “Haystack” for Regenerative Medicine-Based Applications

2022 ◽  
Vol 2022 ◽  
pp. 1-20
Author(s):  
Zi Y. Kok ◽  
Nadia Y. A. Alaidaroos ◽  
Amr Alraies ◽  
John S. Colombo ◽  
Lindsay C. Davies ◽  
...  
Keyword(s):  
Stem Cell ◽  
Regenerative Medicine ◽  
Stromal Cells ◽  
Dental Pulp ◽  
Laboratory Research ◽  
Specific Cell ◽  
Metabolic Markers ◽  
Isolation And Purification ◽  
Human Dental Pulp ◽  
Cell Niche

Human dental pulp stem/stromal cells (hDPSCs) derived from the permanent secondary dentition are recognised to possess certain advantageous traits, which support their potential use as a viable source of mesenchymal stem/stromal cells (MSCs) for regenerative medicine-based applications. However, the well-established heterogeneous nature of hDPSC subpopulations, coupled with their limited numbers within dental pulp tissues, has impeded our understanding of hDPSC biology and the translation of sufficient quantities of these cells from laboratory research, through successful therapy development and clinical applications. This article reviews our current understanding of hDPSC biology and the evidence underpinning the molecular basis of their heterogeneity, which may be exploited to distinguish individual subpopulations with specific or superior characteristics for regenerative medicine applications. Pertinent unanswered questions which still remain, regarding the developmental origins, hierarchical organisation, and stem cell niche locations of hDPSC subpopulations and their roles in hDPSC heterogeneity and functions, will further be explored. Ultimately, a greater understanding of how key features, such as specific cell surface, senescence and other relevant genes, and protein and metabolic markers, delineate between hDPSC subpopulations with contrasting stemness, proliferative, multipotency, immunomodulatory, anti-inflammatory, and other relevant properties is required. Such knowledge advancements will undoubtedly lead to the development of novel screening, isolation, and purification strategies, permitting the routine and effective identification, enrichment, and expansion of more desirable hDPSC subpopulations for regenerative medicine-based applications. Furthermore, such innovative measures could lead to improved cell expansion, manufacture, and banking procedures, thereby supporting the translational development of hDPSC-based therapies in the future.

Plasticity of human dental pulp stromal cells with bioengineering platforms: A versatile tool for regenerative medicine

Micron ◽  
2014 ◽  
Vol 67 ◽  
pp. 155-168 ◽  
Author(s):  
Serena Barachini ◽  
Serena Danti ◽  
Simone Pacini ◽  
Delfo D’Alessandro ◽  
Vittoria Carnicelli ◽  
...  
Keyword(s):  
Regenerative Medicine ◽  
Stromal Cells ◽  
Dental Pulp ◽  
Versatile Tool ◽  
Human Dental Pulp

Human Dental Pulp Stem Cell Behavior Using Natural Nanotolith/Bacterial Cellulose Scaffolds for Regenerative Medicine

2013 ◽  
Vol 9 (8) ◽  
pp. 1370-1377 ◽  
Author(s):  
Gabriel Molina Olyveira ◽  
Gerson Arisoly Xavier Acasigua ◽  
Ligia Maria Manzine Costa ◽  
Cristiane Regina Scher ◽  
Lauro Xavier Filho ◽  
...  
Keyword(s):  
Stem Cell ◽  
Regenerative Medicine ◽  
Bacterial Cellulose ◽  
Dental Pulp ◽  
Cell Behavior ◽  
Human Dental Pulp ◽  
Dental Pulp Stem Cell

scholarly journals The Selective Histone Deacetylase Inhibitor MI192 Enhances the Osteogenic Differentiation Efficacy of Human Dental Pulp Stromal Cells

2021 ◽  
Vol 22 (10) ◽  
pp. 5224
Author(s):  
Kenny Man ◽  
Liam Lawlor ◽  
Lin-Hua Jiang ◽  
Xuebin B. Yang
Keyword(s):  
Alkaline Phosphatase ◽  
Osteogenic Differentiation ◽  
Stromal Cells ◽  
Dental Pulp ◽  
Selective Inhibitor ◽  
Epigenetic Reprogramming ◽  
Type I ◽  
Human Dental Pulp ◽  
Pre Treatment ◽  
Dose Dependent

The use of human dental pulp stromal cells (hDPSCs) has gained increasing attention as an alternative stem cell source for bone tissue engineering. The modification of the cells’ epigenetics has been found to play an important role in regulating differentiation, with the inhibition of histone deacetylases 3 (HDAC3) being linked to increased osteogenic differentiation. This study aimed to induce epigenetic reprogramming using the HDAC2 and 3 selective inhibitor, MI192 to promote hDPSCs osteogenic capacity for bone regeneration. MI192 treatment caused a time–dose-dependent change in hDPSC morphology and reduction in viability. Additionally, MI192 successfully augmented hDPSC epigenetic functionality, which resulted in increased histone acetylation and cell cycle arrest at the G2/M phase. MI192 pre-treatment exhibited a dose-dependent effect on hDPSCs alkaline phosphatase activity. Quantitative PCR and In-Cell Western further demonstrated that MI192 pre-treatment significantly upregulated hDPSCs osteoblast-related gene and protein expression (alkaline phosphatase, bone morphogenic protein 2, type I collagen and osteocalcin) during osteogenic differentiation. Importantly, MI192 pre-treatment significantly increased hDPSCs extracellular matrix collagen production and mineralisation. As such, for the first time, our findings show that epigenetic reprogramming with the HDAC2 and 3 selective inhibitor MI192 accelerates the osteogenic differentiation of hDPSCs, demonstrating the considerable utility of this MSCs engineering approach for bone augmentation strategies.

scholarly journals Differential SOD2 and GSTZ1 profiles contribute to contrasting dental pulp stem cell susceptibilities to oxidative damage and premature senescence

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nadia Y. A. Alaidaroos ◽  
Amr Alraies ◽  
Rachel J. Waddington ◽  
Alastair J. Sloan ◽  
Ryan Moseley
Keyword(s):  
Stem Cell ◽  
Regenerative Medicine ◽  
Oxidative Damage ◽  
Dental Pulp ◽  
Stem Cell Marker ◽  
Significant Heterogeneity ◽  
Premature Senescence ◽  
Cell Marker ◽  
Marker Expression ◽  
The Impact

Abstract Background Dental pulp stem cells (DPSCs) are increasingly being advocated as viable cell sources for regenerative medicine-based therapies. However, significant heterogeneity in DPSC expansion and multi-potency capabilities are well-established, attributed to contrasting telomere profiles and susceptibilities to replicative senescence. As DPSCs possess negligible human telomerase (hTERT) expression, we examined whether intrinsic differences in the susceptibilities of DPSC sub-populations to oxidative stress-induced biomolecular damage and premature senescence further contributed to this heterogeneity, via differential enzymic antioxidant capabilities between DPSCs. Methods DPSCs were isolated from human third molars by differential fibronectin adhesion, and positive mesenchymal (CD73/CD90/CD105) and negative hematopoietic (CD45) stem cell marker expression confirmed. Isolated sub-populations were expanded in H2O2 (0–200 μM) and established as high or low proliferative DPSCs, based on population doublings (PDs) and senescence (telomere lengths, SA-β-galactosidase, p53/p16INK4a/p21waf1/hTERT) marker detection. The impact of DPSC expansion on mesenchymal, embryonic, and neural crest marker expression was assessed, as were the susceptibilities of high and low proliferative DPSCs to oxidative DNA and protein damage by immunocytochemistry. Expression profiles for superoxide dismutases (SODs), catalase, and glutathione-related antioxidants were further compared between DPSC sub-populations by qRT-PCR, Western blotting and activity assays. Results High proliferative DPSCs underwent > 80PDs in culture and resisted H2O2−induced senescence (50–76PDs). In contrast, low proliferative sub-populations exhibited accelerated senescence (4–32PDs), even in untreated controls (11-34PDs). While telomere lengths were largely unaffected, certain stem cell marker expression declined with H2O2 treatment and expansion. Elevated senescence susceptibilities in low proliferative DPSC (2–10PDs) were accompanied by increased oxidative damage, absent in high proliferative DPSCs until 45–60PDs. Increased SOD2/glutathione S-transferase ζ1 (GSTZ1) expression and SOD activities were identified in high proliferative DPSCs (10–25PDs), which declined during expansion. Low proliferative DPSCs (2–10PDs) exhibited inferior SOD, catalase and glutathione-related antioxidant expression/activities. Conclusions Significant variations exist in the susceptibilities of DPSC sub-populations to oxidative damage and premature senescence, contributed to by differential SOD2 and GSTZ1 profiles which maintain senescence-resistance/stemness properties in high proliferative DPSCs. Identification of superior antioxidant properties in high proliferative DPSCs enhances our understanding of DPSC biology and senescence, which may be exploited for selective sub-population screening/isolation from dental pulp tissues for regenerative medicine-based applications.

scholarly journals Goals and Challenges of Stem Cell-Based Therapy for Corneal Blindness Due to Limbal Deficiency

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1483
Author(s):  
Margarita Calonge ◽  
Teresa Nieto-Miguel ◽  
Ana de la Mata ◽  
Sara Galindo ◽  
José M. Herreras ◽  
...  
Keyword(s):  
Stem Cell ◽  
Regenerative Medicine ◽  
Stem Cell Niche ◽  
Basic Research ◽  
Cell Based Therapy ◽  
Novel Approach ◽  
Corneal Blindness ◽  
Limbal Stem Cell ◽  
Cell Niche ◽  
The Right

Corneal failure is a highly prevalent cause of blindness. One special cause of corneal failure occurs due to malfunction or destruction of the limbal stem cell niche, upon which the superficial cornea depends for homeostatic maintenance and wound healing. Failure of the limbal niche is referred to as limbal stem cell deficiency. As the corneal epithelial stem cell niche is easily accessible, limbal stem cell-based therapy and regenerative medicine applied to the ocular surface are among the most highly advanced forms of this novel approach to disease therapy. However, the challenges are still great, including the development of cell-based products and understanding how they work in the patient’s eye. Advances are being made at the molecular, cellular, and tissue levels to alter disease processes and to reduce or eliminate blindness. Efforts must be coordinated from the most basic research to the most clinically oriented projects so that cell-based therapies can become an integrated part of the therapeutic armamentarium to fight corneal blindness. We undoubtedly are progressing along the right path because cell-based therapy for eye diseases is one of the most successful examples of global regenerative medicine.

Sign in / Sign up

Export Citation Format

Share Document