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Transplantation of cultured dental pulp stem cells into the skeletal muscles ameliorated diabetic polyneuropathy: therapeutic plausibility of freshly isolated and cryopreserved dental pulp stem cells.

Hata M, Omi M, Kobayashi Y, Nakamura N, Tosaki T, Miyabe M, Kojima N, Kubo K, Ozawa S, Maeda H, Tanaka Y, Matsubara T, Naruse K - Stem Cell Res Ther (2015)

Bottom Line: Obtained DPSCs can be cryopreserved until necessary and thawed and expanded when needed.Transplantation of DPSCs significantly improved the impaired sciatic nerve blood flow, sciatic motor/sensory nerve conduction velocity, capillary number to muscle fiber ratio and intra-epidermal nerve fiber density in the transplanted side of diabetic rats.Cryopreservation of DPSCs did not impair their proliferative or differential ability.

View Article: PubMed Central - PubMed

Affiliation: Department of Removable Prosthodontics, School of Dentistry, Aichi Gakuin University, Nagoya, Japan. hata@dpc.agu.ac.jp.

ABSTRACT

Introduction: Dental pulp stem cells (DPSCs) are mesenchymal stem cells located in dental pulp and are thought to be a potential source for cell therapy since DPSCs can be easily obtained from teeth extracted for orthodontic reasons. Obtained DPSCs can be cryopreserved until necessary and thawed and expanded when needed. The aim of this study is to evaluate the therapeutic potential of DPSC transplantation for diabetic polyneuropathy.

Methods: DPSCs isolated from the dental pulp of extracted incisors of Sprague-Dawley rats were partly frozen in a -80 °C freezer for 6 months. Cultured DPSCs were transplanted into the unilateral hindlimb skeletal muscles 8 weeks after streptozotocine injection and the effects of DPSC transplantation were evaluated 4 weeks after the transplantation.

Results: Transplantation of DPSCs significantly improved the impaired sciatic nerve blood flow, sciatic motor/sensory nerve conduction velocity, capillary number to muscle fiber ratio and intra-epidermal nerve fiber density in the transplanted side of diabetic rats. Cryopreservation of DPSCs did not impair their proliferative or differential ability. The transplantation of cryopreserved DPSCs ameliorated sciatic nerve blood flow and sciatic nerve conduction velocity as well as freshly isolated DPSCs.

Conclusions: We demonstrated the effectiveness of DPSC transplantation for diabetic polyneuropathy even when using cryopreserved DPSCs, suggesting that the transplantation of DPSCs could be a promising tool for the treatment of diabetic neuropathy.

No MeSH data available.


Related in: MedlinePlus

Capillaries in the soleus muscles. a, b Representative photomicrographs of the histological sections in the skeletal muscles of normal and diabetic rats. Capillaries were visualized by von Willebrand factor (vWF) (a) and PECAM-1 (b). Arrows indicate vascular endothelial cells stained by vWF. Bar = 50μm. c Quantitative analysis for capillary to muscle fiber ratio of the skeletal muscles of normal and diabetic rats. Results are expressed as means ± SEM (n = 4). **P < 0.01. d Differentiation of transplanted green fluorescent protein (GFP)-expressing dental pulp stem cells (DPSCs) into vascular endothelial cells in the skeletal muscles 4 weeks after the transplantation. DPSCs from GFP-expressing rats were transplanted into hindlimb skeletal muscles in the diabetic rats. Vascular endothelial cells were visualized by PECAM-1. Bar = 50 μm
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Fig3: Capillaries in the soleus muscles. a, b Representative photomicrographs of the histological sections in the skeletal muscles of normal and diabetic rats. Capillaries were visualized by von Willebrand factor (vWF) (a) and PECAM-1 (b). Arrows indicate vascular endothelial cells stained by vWF. Bar = 50μm. c Quantitative analysis for capillary to muscle fiber ratio of the skeletal muscles of normal and diabetic rats. Results are expressed as means ± SEM (n = 4). **P < 0.01. d Differentiation of transplanted green fluorescent protein (GFP)-expressing dental pulp stem cells (DPSCs) into vascular endothelial cells in the skeletal muscles 4 weeks after the transplantation. DPSCs from GFP-expressing rats were transplanted into hindlimb skeletal muscles in the diabetic rats. Vascular endothelial cells were visualized by PECAM-1. Bar = 50 μm

Mentions: The vasculatures in the soleus muscles were visualized by vWF immunostaining (Fig. 3a) and PECAM-1 immunofluorescence staining (Fig. 3b). Quantitative analyses revealed that the PECAM-1 positive endothelial cell to muscle fiber ratio was significantly reduced in the vehicle-injected side of diabetic rats compared with the normal rats (P < 0.01) (Fig. 3c). Transplantation of DPSCs significantly increased the PECAM-1 positive cell to muscle ratio in diabetic rats.Fig. 3


Transplantation of cultured dental pulp stem cells into the skeletal muscles ameliorated diabetic polyneuropathy: therapeutic plausibility of freshly isolated and cryopreserved dental pulp stem cells.

Hata M, Omi M, Kobayashi Y, Nakamura N, Tosaki T, Miyabe M, Kojima N, Kubo K, Ozawa S, Maeda H, Tanaka Y, Matsubara T, Naruse K - Stem Cell Res Ther (2015)

Capillaries in the soleus muscles. a, b Representative photomicrographs of the histological sections in the skeletal muscles of normal and diabetic rats. Capillaries were visualized by von Willebrand factor (vWF) (a) and PECAM-1 (b). Arrows indicate vascular endothelial cells stained by vWF. Bar = 50μm. c Quantitative analysis for capillary to muscle fiber ratio of the skeletal muscles of normal and diabetic rats. Results are expressed as means ± SEM (n = 4). **P < 0.01. d Differentiation of transplanted green fluorescent protein (GFP)-expressing dental pulp stem cells (DPSCs) into vascular endothelial cells in the skeletal muscles 4 weeks after the transplantation. DPSCs from GFP-expressing rats were transplanted into hindlimb skeletal muscles in the diabetic rats. Vascular endothelial cells were visualized by PECAM-1. Bar = 50 μm
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4562193&req=5

Fig3: Capillaries in the soleus muscles. a, b Representative photomicrographs of the histological sections in the skeletal muscles of normal and diabetic rats. Capillaries were visualized by von Willebrand factor (vWF) (a) and PECAM-1 (b). Arrows indicate vascular endothelial cells stained by vWF. Bar = 50μm. c Quantitative analysis for capillary to muscle fiber ratio of the skeletal muscles of normal and diabetic rats. Results are expressed as means ± SEM (n = 4). **P < 0.01. d Differentiation of transplanted green fluorescent protein (GFP)-expressing dental pulp stem cells (DPSCs) into vascular endothelial cells in the skeletal muscles 4 weeks after the transplantation. DPSCs from GFP-expressing rats were transplanted into hindlimb skeletal muscles in the diabetic rats. Vascular endothelial cells were visualized by PECAM-1. Bar = 50 μm
Mentions: The vasculatures in the soleus muscles were visualized by vWF immunostaining (Fig. 3a) and PECAM-1 immunofluorescence staining (Fig. 3b). Quantitative analyses revealed that the PECAM-1 positive endothelial cell to muscle fiber ratio was significantly reduced in the vehicle-injected side of diabetic rats compared with the normal rats (P < 0.01) (Fig. 3c). Transplantation of DPSCs significantly increased the PECAM-1 positive cell to muscle ratio in diabetic rats.Fig. 3

Bottom Line: Obtained DPSCs can be cryopreserved until necessary and thawed and expanded when needed.Transplantation of DPSCs significantly improved the impaired sciatic nerve blood flow, sciatic motor/sensory nerve conduction velocity, capillary number to muscle fiber ratio and intra-epidermal nerve fiber density in the transplanted side of diabetic rats.Cryopreservation of DPSCs did not impair their proliferative or differential ability.

View Article: PubMed Central - PubMed

Affiliation: Department of Removable Prosthodontics, School of Dentistry, Aichi Gakuin University, Nagoya, Japan. hata@dpc.agu.ac.jp.

ABSTRACT

Introduction: Dental pulp stem cells (DPSCs) are mesenchymal stem cells located in dental pulp and are thought to be a potential source for cell therapy since DPSCs can be easily obtained from teeth extracted for orthodontic reasons. Obtained DPSCs can be cryopreserved until necessary and thawed and expanded when needed. The aim of this study is to evaluate the therapeutic potential of DPSC transplantation for diabetic polyneuropathy.

Methods: DPSCs isolated from the dental pulp of extracted incisors of Sprague-Dawley rats were partly frozen in a -80 °C freezer for 6 months. Cultured DPSCs were transplanted into the unilateral hindlimb skeletal muscles 8 weeks after streptozotocine injection and the effects of DPSC transplantation were evaluated 4 weeks after the transplantation.

Results: Transplantation of DPSCs significantly improved the impaired sciatic nerve blood flow, sciatic motor/sensory nerve conduction velocity, capillary number to muscle fiber ratio and intra-epidermal nerve fiber density in the transplanted side of diabetic rats. Cryopreservation of DPSCs did not impair their proliferative or differential ability. The transplantation of cryopreserved DPSCs ameliorated sciatic nerve blood flow and sciatic nerve conduction velocity as well as freshly isolated DPSCs.

Conclusions: We demonstrated the effectiveness of DPSC transplantation for diabetic polyneuropathy even when using cryopreserved DPSCs, suggesting that the transplantation of DPSCs could be a promising tool for the treatment of diabetic neuropathy.

No MeSH data available.


Related in: MedlinePlus