Synergistic effect of stem cells from human exfoliated deciduous teeth and rhBMP-2 delivered by injectable nanofibrous microspheres with different surface modifications on vascularized bone regeneration

Abstract Stem cells from human exfoliated deciduous teeth (SHED) possess bone regeneration ability and may have therapeutic applications. CD146, a cell adhesion protein expressed by vascular endothelial cells, is involved in the osteoblastic differentiation of stem cells. However, the effect of CD146 on SHED-mediated bone regeneration in vivo remains unknown. Hence, in this study we aimed to establish efficient conditions for SHED transplantation. SHED were isolated from the pulp of an extracted deciduous tooth and cultured, and CD146-positive (CD146+) and CD146-negative (CD146−) populations were sorted. Heterogeneous populations of SHED and CD146+ and CD146– cells were transplanted into bone defects generated in the skulls of individual immunodeficient mice. Micro-computed tomography was performed immediately post-transplantation and at 4- and 8-weeks thereafter to evaluate bone regeneration. Histological and immunohistochemical assessments were also performed at 8 weeks after transplantation. Micro-computed tomography revealed bone regeneration upon transplantation with CD146+ and heterogeneous populations of SHED, particularly at 8 weeks after transplantation, with significantly higher bone regeneration observed following transplantation with CD146+ cells. Furthermore, histological and immunohistochemical assessments revealed that CD146+ cells promoted bone regeneration and angiogenesis. Therefore, transplantation of CD146+ SHED into bone defects may serve as a useful strategy for bone regeneration.

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The Immunologic Properties of Undifferentiated Stem Cells from Human Exfoliated Deciduous Teeth (SHED) and Its Potential Application in Bone Regeneration

IIUM Medical Journal Malaysia ◽

10.31436/imjm.v12i1.1997 ◽

2013 ◽

Vol 12 (1) ◽

Author(s):

Dr. Nurul Asma Abdullah

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Therapy ◽

Bone Regeneration ◽

Inflammatory Cytokines ◽

Stem Cell Therapy ◽

Reverse Transcription ◽

Deciduous Teeth ◽

Tnf Α ◽

Human Exfoliated Deciduous Teeth

Introduction: Stem cells from human exfoliated deciduous teeth (SHED) are highly proliferative, clonogenic cells capable of differentiating into osteoblasts and inducing bone formation. It is a potential alternative for stem cell bone regeneration therapy. However, stem cell therapy carries the risk of immune rejection mediated by inflammatory cytokines of the human defense system. Objective: This preliminary research studies the interaction between SHED and the immune system by determining the inflammatory cytokines profile and osteogenic potential of SHED. Methods: Human fetal osteoblasts (hFOb) cell line and isolated SHED were cultured and total RNA was extracted, followed by reverse transcription cDNA synthesis. Semi-quantitative reverse transcription PCR and Multiplex PCR were performed to detect the expression levels of OPG/RANKL and TNF-α, IL-1β, IL-6, IL-8 and TGF-β in both cell types. Results: Analysis showed that SHED expressed significantly lower amounts of IL-1β, IL-6, and IL-8 compared to hFOB. IL-1β is a potent bone-resorbing factor, while IL-6 and IL-8 induce osteoclastogenesis and osteolysis respectively. SHED did not express TNF-α which stimulates osteoclastic activity. SHED demonstrated high OPG/RANKL ratio, in contrast with that of marrow stem cells described in previous studies. Our findings suggest that SHED may have improved immunomodulatory profile in terms of promoting relatively lower inflammatory reaction during transplant and enhancing bone regeneration. Conclusion: SHED has a potential to be a good source of osteoblasts for bone regeneration therapy. Further studies on the immunomodulatory properties of SHED-derived osteoblasts are necessary to enable stem cell therapy in immunocompetent hosts

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Knowledge and awareness on the stem cells from human exfoliated deciduous teeth among dental students

International Journal of Pharmaceutical Research ◽

10.31838/ijpr/2020.sp2.407 ◽

2020 ◽

Vol 12 (sp2) ◽

Keyword(s):

Stem Cells ◽

Dental Students ◽

Deciduous Teeth ◽

Human Exfoliated Deciduous Teeth

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Stem Cells Derived from Human Exfoliated Deciduous teeth [shed] in Neuronal Disorders: A Review

Current Stem Cell Research & Therapy ◽

10.2174/1574888x16666201221151512 ◽

2020 ◽

Vol 16 ◽

Author(s):

Minu Anoop ◽

Indrani Datta

Keyword(s):

Stem Cells ◽

Neurodegenerative Diseases ◽

Dental Pulp ◽

Therapeutic Potential ◽

Permanent Teeth ◽

Deciduous Teeth ◽

Proliferative Potential ◽

Pulp Tissue ◽

Human Exfoliated Deciduous Teeth

: Most conventional treatments for neurodegenerative diseases fail due to their focus on neuroprotection rather than neurorestoration. Stem cell‐based therapies are becoming a potential treatment option for neurodegenerative diseases as they can home in, engraft, differentiate and produce factors for CNS recovery. Stem cells derived from human dental pulp tissue differ from other sources of mesenchymal stem cells due to their embryonic neural crest origin and neurotrophic property. These include both dental pulp stem cells [DPSCs] from dental pulp tissues of human permanent teeth and stem cells from human exfoliated deciduous teeth [SHED]. SHED offer many advantages over other types of MSCs such as good proliferative potential, minimal invasive procurement, neuronal differentiation and neurotrophic capacity, and negligible ethical concerns. The therapeutic potential of SHED is attributed to the paracrine action of extracellularly released secreted factors, specifically the secretome, of which exosomes is a key component. SHED and its conditioned media can be effective in neurodegeneration through multiple mechanisms, including cell replacement, paracrine effects, angiogenesis, synaptogenesis, immunomodulation, and apoptosis inhibition, and SHED exosomes offer an ideal refined bed-to-bench formulation in neurodegenerative disorders. However, in spite of these advantages, there are still some limitations of SHED exosome therapy, such as the effectiveness of long-term storage of SHED and their exosomes, the development of a robust GMP-grade manufacturing protocol, optimization of the route of administration, and evaluation of the efficacy and safety in humans. In this review, we have addressed the isolation, collection and properties of SHED along with its therapeutic potential on in vitro and in vivo neuronal disorder models as evident from the published literature.

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