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

Author(s):  
Koichiro Yoshimaru ◽  
Takayoshi Yamaza ◽  
Shunichi Kajioka ◽  
Soichiro Sonoda ◽  
Yusuke Yanagi ◽  
...  

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.

2021 ◽  
Author(s):  
Shunichi Kajioka ◽  
Junko Yoshizumi ◽  
Yoshinao Oda ◽  
Naoko Iwata ◽  
Chiho Takai ◽  
...  

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.


2021 ◽  
Author(s):  
Koichiro Yoshimaru ◽  
Takayoshi Yamaza ◽  
Shunichi Kajioka ◽  
Soichiro Sonoda ◽  
Yusuke Yanagi ◽  
...  

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.


2021 ◽  
Author(s):  
Koichiro Yoshimaru ◽  
Takayoshi Yamaza ◽  
Shunichi Kajioka ◽  
Soichiro Sonoda ◽  
Yusuke Yanagi ◽  
...  

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.


2021 ◽  
Author(s):  
Shunichi Kajioka ◽  
Junko Yoshizumi ◽  
Yoshinao Oda ◽  
Naoko Iwata ◽  
Chiho Takai ◽  
...  

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.


2021 ◽  
Author(s):  
Koichiro Yoshimaru ◽  
Takayoshi Yamaza ◽  
Shunichi Kajioka ◽  
Soichiro Sonoda ◽  
Yusuke Yanagi ◽  
...  

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.


2008 ◽  
Vol 55 (3) ◽  
pp. 170-179 ◽  
Author(s):  
Vera Todorovic ◽  
Dejan Markovic ◽  
Nadezda Milosevic-Jovcic ◽  
Marijana Petakov ◽  
Bela Balint ◽  
...  

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.


Development ◽  
2002 ◽  
Vol 129 (12) ◽  
pp. 2785-2796 ◽  
Author(s):  
Alan J. Burns ◽  
Jean-Marie M. Delalande ◽  
Nicole M. Le Douarin

The enteric nervous system (ENS) is derived from vagal and sacral neural crest cells (NCC). Within the embryonic avian gut, vagal NCC migrate in a rostrocaudal direction to form the majority of neurons and glia along the entire length of the gastrointestinal tract, whereas sacral NCC migrate in an opposing caudorostral direction, initially forming the nerve of Remak, and contribute a smaller number of ENS cells primarily to the distal hindgut. In this study, we have investigated the ability of vagal NCC, transplanted to the sacral region of the neuraxis, to colonise the chick hindgut and form the ENS in an experimentally generated hypoganglionic hindgut in ovo model. Results showed that when the vagal NC was transplanted into the sacral region of the neuraxis, vagal-derived ENS precursors immediately migrated away from the neural tube along characteristic pathways, with numerous cells colonising the gut mesenchyme by embryonic day (E) 4. By E7, the colorectum was extensively colonised by transplanted vagal NCC and the migration front had advanced caudorostrally to the level of the umbilicus. By E10, the stage at which sacral NCC begin to colonise the hindgut in large numbers, myenteric and submucosal plexuses in the hindgut almost entirely composed of transplanted vagal NCC, while the migration front had progressed into the pre-umbilical intestine, midway between the stomach and umbilicus. Immunohistochemical staining with the pan-neuronal marker, ANNA-1, revealed that the transplanted vagal NCC differentiated into enteric neurons, and whole-mount staining with NADPH-diaphorase showed that myenteric and submucosal ganglia formed interconnecting plexuses, similar to control animals. Furthermore, using an anti-RET antibody, widespread immunostaining was observed throughout the ENS, within a subpopulation of sacral NC-derived ENS precursors, and in the majority of transplanted vagal-to-sacral NCC. Our results demonstrate that: (1) a cell autonomous difference exists between the migration/signalling mechanisms used by sacral and vagal NCC, as transplanted vagal cells migrated along pathways normally followed by sacral cells, but did so in much larger numbers, earlier in development; (2) vagal NCC transplanted into the sacral neuraxis extensively colonised the hindgut, migrated in a caudorostral direction, differentiated into neuronal phenotypes, and formed enteric plexuses; (3) RET immunostaining occurred in vagal crest-derived ENS cells, the nerve of Remak and a subpopulation of sacral NCC within hindgut enteric ganglia.


2019 ◽  
Vol 35 (4) ◽  
Author(s):  
Shagufta Naz ◽  
Farhan Raza Khan ◽  
Raheela Rahmat Zohra ◽  
Sahreena Salim Lakhundi ◽  
Mehwish Sagheer Khan ◽  
...  

Objective: To isolate dental pulp mesenchymal stem cells (MSCs) from non-infected human permanent and deciduous teeth. Methods: It was an in-vitro experimental study. Human teeth were collected from 13 apparently healthy subjects including nine adults and four children. After decoronation dental pulps were extirpated from teeth and cultured via explant method in a stem cell defined media. Data was analyzed by descriptive statistics. Results: As above MSCs emerged exhibiting fibroblast-like morphology. In vitro culture was positive for 100% (9/9) and 75% (3/4) of the permanent and deciduous teeth respectively. First cell appeared from deciduous teeth pulp in 10±6.2 days while permanent teeth pulp took 12.4±3.7 days. Together, 26.6±3.6 and 24.5±3.5 days were required for permanent and deciduous tooth pulp stem cells to be ready for further assays. Conclusions: The protocol we developed is easy and consistent and can be used to generate reliable source of MScs for engineering of calcified and non-calcified tissue for regenerative medicine approaches. doi: https://doi.org/10.12669/pjms.35.4.540 How to cite this:Naz S, Khan FR, Zohra RR, Lakhundi SS, Khan MS, Mohammed N, et al. Isolation and culture of dental pulp stem cells from permanent and deciduous teeth. Pak J Med Sci. 2019;35(4):---------. doi: https://doi.org/10.12669/pjms.35.4.540 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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