Dental pulp stem cells as a therapy for congenital entero-neuropathy

Abstract Hirschsprung’s disease (HSCR) and its allied disorders are congenital entero-neuropathies with life-long implications in many cases. Here we report the effects of intravenous transplantation of cultured dental pulp stem cells derived from deciduous teeth (dDPSCs) into ‘Japanese fancy-1’ (JF1) mice with entero-neuropathy caused by Ednrb mutation. Intravenously injected dDPSCs (multipotent neural crest cells with low immunogenicity) migrated to affected regions of the intestine through interactions between stromal cell-derived factor-1α and C-X-C chemokine receptor type-4. Notably, transplanted dDPSCs differentiated into both enteric neurons and pacemaker interstitial cells to correct abnormalities in the electrical and mechanical activities of the proximal colon. dDPSC transplantation also led to repair of the small intestinal mucosa, changes in the gastrointestinal microbiota, improvements in nutritional status and prolongation of survival. We anticipate that dDPSC transplantation could be developed into a novel cell-based therapy for HSCR and its allied disorders.

Download Full-text

Dental pulp stem cells as a therapy for congenital entero-neuropathy

10.21203/rs.3.rs-596893/v4 ◽

2021 ◽

Author(s):

Koichiro Yoshimaru ◽

Takayoshi Yamaza ◽

Shunichi Kajioka ◽

Soichiro Sonoda ◽

Yusuke Yanagi ◽

...

Keyword(s):

Stem Cells ◽

Dental Pulp ◽

Proximal Colon ◽

Dental Pulp Stem Cells ◽

Enteric Neurons ◽

Deciduous Teeth ◽

Small Intestinal Mucosa ◽

Gastrointestinal Microbiota ◽

Cell Based Therapy ◽

Stromal Cell Derived Factor

Abstract Hirschsprung’s disease (HSCR) and its allied disorders are congenital entero-neuropathies with life-long implications in many cases. Here we report the effects of intravenous transplantation of cultured dental pulp stem cells derived from deciduous teeth (dDPSCs) into ‘Japanese fancy-1’ (JF1) mice with entero-neuropathy caused by Ednrb mutation. Intravenously injected dDPSCs (multipotent neural crest cells with low immunogenicity) migrated to affected regions of the intestine through interactions between stromal cell-derived factor-1α and C-X-C chemokine receptor type-4. Notably, transplanted dDPSCs differentiated into both enteric neurons and pacemaker interstitial cells to correct abnormalities in the electrical and mechanical activities of the proximal colon. dDPSC transplantation also led to repair of the small intestinal mucosa, changes in the gastrointestinal microbiota, improvements in nutritional status and prolongation of survival. We anticipate that dDPSC transplantation could be developed into a novel cell-based therapy for HSCR and its allied disorders.

Download Full-text

Dental pulp stem cells as a therapy for congenital entero-neuropathy

10.21203/rs.3.rs-596893/v1 ◽

2021 ◽

Author(s):

Shunichi Kajioka ◽

Junko Yoshizumi ◽

Yoshinao Oda ◽

Naoko Iwata ◽

Chiho Takai ◽

...

Keyword(s):

Stem Cells ◽

Dental Pulp ◽

Proximal Colon ◽

Dental Pulp Stem Cells ◽

Enteric Neurons ◽

Deciduous Teeth ◽

Small Intestinal Mucosa ◽

Gastrointestinal Microbiota ◽

Cell Based Therapy ◽

Stromal Cell Derived Factor

Abstract Hirschsprung’s disease (HSCR) and its allied disorders are congenital entero-neuropathies with life-long implications in many cases. Here we report the effects of intravenous transplantation of cultured dental pulp stem cells derived from deciduous teeth (dDPSCs) into ‘Japanese fancy-1’ (JF1) mice with entero-neuropathy caused by Ednrb mutation. Intravenously injected dDPSCs (multipotent neural crest cells with low immunogenicity) migrated to affected regions of the intestine through interactions between stromal cell-derived factor-1α and C-X-C chemokine receptor type-4. Notably, transplanted dDPSCs differentiated into both enteric neurons and pacemaker interstitial cells to correct abnormalities in the electrical and mechanical activities of the proximal colon. dDPSC transplantation also led to repair of the small intestinal mucosa, changes in the gastrointestinal microbiota, improvements in nutritional status and prolongation of survival. We anticipate that dDPSC transplantation could be developed into a novel cell-based therapy for HSCR and its allied disorders.

Download Full-text

Dental pulp stem cells as a therapy for congenital entero-neuropathy

10.21203/rs.3.rs-596893/v5 ◽

2021 ◽

Author(s):

Koichiro Yoshimaru ◽

Takayoshi Yamaza ◽

Shunichi Kajioka ◽

Soichiro Sonoda ◽

Yusuke Yanagi ◽

...

Keyword(s):

Stem Cells ◽

Dental Pulp ◽

Proximal Colon ◽

Dental Pulp Stem Cells ◽

Enteric Neurons ◽

Deciduous Teeth ◽

Small Intestinal Mucosa ◽

Gastrointestinal Microbiota ◽

Cell Based Therapy ◽

Stromal Cell Derived Factor

Abstract Hirschsprung’s disease (HSCR) and its allied disorders are congenital entero-neuropathies with life-long implications in many cases. Here we report the effects of intravenous transplantation of cultured dental pulp stem cells derived from deciduous teeth (dDPSCs) into ‘Japanese fancy-1’ (JF1) mice with entero-neuropathy caused by Ednrb mutation. Intravenously injected dDPSCs (multipotent neural crest cells with low immunogenicity) migrated to affected regions of the intestine through interactions between stromal cell-derived factor-1α and C-X-C chemokine receptor type-4. Notably, transplanted dDPSCs differentiated into both enteric neurons and pacemaker interstitial cells to correct abnormalities in the electrical and mechanical activities of the proximal colon. dDPSC transplantation also led to repair of the small intestinal mucosa, changes in the gastrointestinal microbiota, improvements in nutritional status and prolongation of survival. We anticipate that dDPSC transplantation could be developed into a novel cell-based therapy for HSCR and its allied disorders.

Download Full-text

Insight into the Role of Dental Pulp Stem Cells in Regenerative Therapy

Biology ◽

10.3390/biology9070160 ◽

2020 ◽

Vol 9 (7) ◽

pp. 160 ◽

Cited By ~ 5

Author(s):

Shinichiro Yoshida ◽

Atsushi Tomokiyo ◽

Daigaku Hasegawa ◽

Sayuri Hamano ◽

Hideki Sugii ◽

...

Keyword(s):

Stem Cells ◽

Tissue Regeneration ◽

Dental Pulp ◽

High Growth ◽

Dental Pulp Stem Cells ◽

Permanent Teeth ◽

Deciduous Teeth ◽

Pulp Tissue ◽

Differentiation Potential ◽

Cell Based Therapy

Mesenchymal stem cells (MSCs) have the capacity for self-renewal and multilineage differentiation potential, and are considered a promising cell population for cell-based therapy and tissue regeneration. MSCs are isolated from various organs including dental pulp, which originates from cranial neural crest-derived ectomesenchyme. Recently, dental pulp stem cells (DPSCs) and stem cells from human exfoliated deciduous teeth (SHEDs) have been isolated from dental pulp tissue of adult permanent teeth and deciduous teeth, respectively. Because of their MSC-like characteristics such as high growth capacity, multipotency, expression of MSC-related markers, and immunomodulatory effects, they are suggested to be an important cell source for tissue regeneration. Here, we review the features of these cells, their potential to regenerate damaged tissues, and the recently acquired understanding of their potential for clinical application in regenerative medicine.

Download Full-text

Dental pulp stem cells as a therapy for congenital entero-neuropathy

10.21203/rs.3.rs-596893/v7 ◽

2021 ◽

Author(s):

Koichiro Yoshimaru ◽

Takayoshi Yamaza ◽

Shunichi Kajioka ◽

Soichiro Sonoda ◽

Yusuke Yanagi ◽

...

Keyword(s):

Stem Cells ◽

Nervous System ◽

Neural Crest ◽

Enteric Nervous System ◽

Dental Pulp ◽

Dental Pulp Stem Cells ◽

Enteric Neurons ◽

Deciduous Teeth ◽

Pacemaker Cells ◽

Distal Intestine

Abstract Hirschsprung’s disease is a congenital entero-neuropathy that causes chronic constipation and intestinal obstruction. New treatments for entero-neuropathy are needed because current surgical strategies have limitations5. Entero-neuropathy results from enteric nervous system dysfunction due to incomplete colonization of the distal intestine by neural crest-derived cells. Impaired cooperation between the enteric nervous system and intestinal pacemaker cells may also contribute to entero-neuropathy. Stem cell therapy to repair these multiple defects represents a novel treatment approach. Dental pulp stem cells derived from deciduous teeth (dDPSCs) are multipotent cranial neural crest-derived cells, but it remains unknown whether dDPSCs have potential as a new therapy for entero-neuropathy. Here we show that intravenous transplantation of dDPSCs into the Japanese Fancy-1 mouse, an established model of hypoganglionosis and entero-neuropathy, improves large intestinal structure and function and prolongs survival. Intravenously injected dDPSCs migrate to affected regions of the intestine through interactions between stromal cell-derived factor-1α and C-X-C chemokine receptor type-4. Transplanted dDPSCs differentiate into both pacemaker cells and enteric neurons in the proximal colon to improve electrical and peristaltic activity. Our findings indicate that transplanted dDPSCs can differentiate into different cell types to correct entero-neuropathy-associated defects.

Download Full-text

Dental pulp stem cells: Potential significance in regenerative medicine

Stomatoloski glasnik Srbije ◽

10.2298/sgs0803170t ◽

2008 ◽

Vol 55 (3) ◽

pp. 170-179 ◽

Cited By ~ 5

Author(s):

Vera Todorovic ◽

Dejan Markovic ◽

Nadezda Milosevic-Jovcic ◽

Marijana Petakov ◽

Bela Balint ◽

...

Keyword(s):

Stem Cells ◽

Dental Pulp ◽

Matrix Protein ◽

Dental Pulp Stem Cells ◽

Deciduous Teeth ◽

High Plasticity ◽

Dental Stem Cells ◽

Periodontal Tissues ◽

Extracellular Matrix Components

To date, three types of dental stem cells have been isolated: Dental Pulp Stem Cells (DPSC), Stem Cells From Human Exfoliated Deciduous Teeth (SHED) and Immature Dental Pulp Stem Cells (IDPC). These dental stem cells are considered as mesenchymal stem cells. They reside within the perivascular niche of dental pulp. They are highly proliferative, clonogenic, multipotent and are similar to mesenchymal Bone Marrow Stem Cells (BMSC). Also, they have high plasticity and can be easy isolated. The expressions of the alkaline phosphatase gene, dentin matrix protein 1 and dentinsialophosphoprotein are verified in these cells. Analyses of gene expression patterns indicated several genes which encode extracellular matrix components, cell adhesion molecules, growth factors and transcription regulators, cell signaling, cell communication or cell metabolism. In both conditions, in vivo and in vitro, these cells have the ability to differentiate into odontoblasts, chondrocytes, osteoblasts, adipocytes, neurons, melanocytes, smooth and skeletal muscles and endothelial cells. In vivo, after implantation, they have shown potential to differentiate into dentin but also into tissues like bone, adipose or neural tissue. In general, DPSCs are considered to have antiinflammatory and immunomodulatory abilities. After being grafted into allogenic tissues these cells are ableto induce immunological tolerance. Immunosuppressive effect is shown through the ability to inhibit proliferation of T lymphocytes. Dental pulp stem cells open new perspectives in therapeutic use not only in dentin regeneration, periodontal tissues and skeletoarticular, tissues of craniofacial region but also in treatment of neurotrauma, autoimmune diseases, myocardial infarction, muscular dystrophy and connective tissue damages.

Download Full-text

Protective effect of folic acid on vulnerability to oxidative stress in dental pulp stem cells of deciduous teeth from children with orofacial clefts

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2019.06.031 ◽

2019 ◽

Vol 516 (1) ◽

pp. 127-132 ◽

Cited By ~ 1

Author(s):

Yu Zhang ◽

Xiao Sun ◽

Xu Han ◽

Hiroshi Sato ◽

Yuta Hirofuji ◽

...

Keyword(s):

Oxidative Stress ◽

Stem Cells ◽

Folic Acid ◽

Protective Effect ◽

Dental Pulp ◽

Dental Pulp Stem Cells ◽

Deciduous Teeth ◽

Orofacial Clefts

Download Full-text

Biodistribution of Intramuscularly-Transplanted Human Dental Pulp Stem Cells in Immunocompetent Healthy Rats through NIR Imaging

Cells Tissues Organs ◽

10.1159/000511569 ◽

2020 ◽

pp. 1-12

Author(s):

Pradnya Shahani ◽

Alka Kaushal ◽

Girish Waghmare ◽

Indrani Datta

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Clinical Trials ◽

Blood Vessels ◽

Dental Pulp ◽

Signal Intensity ◽

Dental Pulp Stem Cells ◽

European Medicines Agency ◽

Rat Tissues ◽

Cell Based Therapy

Owing to their neural crest origin, dental pulp stem cells (DPSCs) are increasingly gaining prominence in treating nervous system disease conditions. However, as per the regulatory bodies [European-Medicines Agency (EMA), Indian-Council of Medical-Research (ICMR)], their biodistribution after transplantation needs to be evaluated for them to be considered for cell-based therapy for clinical trials. There are yet no studies describing the dynamic distribution of human origin DPSCs (hDPSCs) after transplantation in an immunocompetent, physiologically healthy animal model. Here, using near-infrared (NIR)-based whole animal and ex vivo tissue imaging, we assessed the biodistribution of intramuscularly transplanted hDPSCs in immunocompetent healthy Wistar rats. Further validation was done by quantifying gene expression of the human Alu gene in rat tissues. After 24 h of transplantation, an increase in signal intensity and area of signal was observed in the muscle of administration compared to 30 min and 6 h. At hour 24, neither increase in human Alu nor human Ki67 gene expression was seen in the rat muscle, thus confirming that the increase in signal area and intensity at hour 24 was not due to proliferation of the transplanted cells. Rather at hour 24, the NIR-signal intensity in bone marrow increased, suggesting that the NIR-tagged DPSCs have started entering into the blood vessels adjacent to the muscle, and the blood vessels being placed just beneath the subcutaneous layer might be responsible for an increase in signal intensity. Signal intensity increased distinctly in all organs at this timepoint, confirming that the cells entered the bloodstream by hour 24. Lung entrapment of DPSCs was not observed, since signal intensity was least in lungs as compared to the site of injection. Cells were retained for up to 28 days at the site of injection. These findings lay the basis to design the dosage for intramuscular delivery of hDPSCs for degenerative disease models and for future clinical trials.

Download Full-text