PMID- 32476103
OWN - NLM
STAT- MEDLINE
DCOM- 20200924
LR  - 20200924
IS  - 1447-073X (Electronic)
IS  - 1447-073X (Linking)
VI  - 95
IP  - 4
DP  - 2020 Sep
TI  - Transplantation of human dental pulp stem cells in streptozotocin-induced 
      diabetic rats.
PG  - 523-539
LID - 10.1007/s12565-020-00550-2 [doi]
AB  - Type 1 diabetes mellitus (T1DM) is a chronic metabolic disease caused by the 
      destruction of pancreatic beta-cells. Human dental pulp stem cells represent a 
      promising source for cell-based therapies, owing to their easy, minimally 
      invasive surgical access, and high proliferative capacity. It was reported that 
      human dental pulp stem cells can differentiate into a pancreatic cell lineage in 
      vitro; however, few studies have investigated their effects on diabetes. Our 
      study aimed to investigate the therapeutic potential of intravenous and 
      intrapancreatic transplantation of human dental pulp stem cells in a rat model of 
      streptozotocin-induced type 1 diabetes. Forty Sprague Dawley male rats were 
      randomly categorized into four groups: control, diabetic (STZ), intravenous 
      treatment group (IV), and intrapancreatic treatment group (IP). Human dental pulp 
      stem cells (1 x 10(6) cells) or vehicle were injected into the pancreas or tail 
      vein 7 days after streptozotocin injection. Fasting blood glucose levels were 
      monitored weekly. Glucose tolerance test, rat and human serum insulin and 
      C-peptide, pancreas histology, and caspase-3, vascular endothelial growth factor, 
      and Ki67 expression in pancreatic tissues were assessed 28 days 
      post-transplantation. We found that both IV and IP transplantation of human 
      dental pulp stem cells reduced blood glucose and increased levels of rat and 
      human serum insulin and C-peptide. The cells engrafted and survived in the 
      streptozotocin-injured pancreas. Islet-like clusters and scattered human dental 
      pulp stem cells expressing insulin were observed in the pancreas of diabetic rats 
      with some difference in the distribution pattern between the two injection 
      routes. RT-PCR analyses revealed the expression of the human-specific pancreatic 
      beta-cell genes neurogenin 3 (NGN3), paired box 4 (PAX4), glucose transporter 2 
      (GLUT2), and insulin in the pancreatic tissues of both the IP and IV groups. In 
      addition, the transplanted cells downregulated the expression of caspase-3 and 
      upregulated the expression of vascular endothelial growth factor and Ki67, 
      suggesting that the injected cells exerted pro-angiogenetic and antiapoptotic 
      effects, and promoted endogenous beta-cell replication. Our study is the first to 
      show that human dental pulp stem cells can migrate and survive within 
      streptozotocin-injured pancreas, and induce antidiabetic effects through the 
      differentiation and replacement of lost beta-cells and paracrine-mediated pancreatic 
      regeneration. Thus, human dental pulp stem cells may have therapeutic potential 
      to treat patients with long term T1DM.
FAU - El-Kersh, Ahmed Othman Fathy Othman
AU  - El-Kersh AOFO
AD  - Faculty of Dentistry, Kafrelsheikh University, Kafrelsheikh, Egypt.
FAU - El-Akabawy, Gehan
AU  - El-Akabawy G
AD  - Department of Basic Sciences, College of Medicine, Princess Nourah Bint 
      Abdulrahman University, Riyadh, Saudi Arabia. gfelakabawy@pnu.edu.sa.
AD  - Department of Anatomy and Embryology, Faculty of Medicine, Menoufia University, 
      Menoufia, Egypt. gfelakabawy@pnu.edu.sa.
FAU - Al-Serwi, Rasha H
AU  - Al-Serwi RH
AD  - Basic Dental Sciences, College of Dentistry, Princess Nourah Bint Abdulrahman 
      University, Riyadh, Saudi Arabia.
AD  - Oral Biology Department, Faculty of Dentistry, Mansoura University, Mansoura, 
      Egypt.
LA  - eng
GR  - Fast track program/Princess Nourah Bint Abdulrahman University/
PT  - Journal Article
DEP - 20200531
PL  - Japan
TA  - Anat Sci Int
JT  - Anatomical science international
JID - 101154140
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (Glucose Transporter Type 2)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Ki-67 Antigen)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neurog3 protein, rat)
RN  - 0 (Paired Box Transcription Factors)
RN  - 0 (Pax4 protein, rat)
RN  - 0 (Slc2a2 protein, rat)
RN  - 5W494URQ81 (Streptozocin)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Animals
MH  - Basic Helix-Loop-Helix Transcription Factors/metabolism
MH  - Caspase 3/metabolism
MH  - Cell Differentiation
MH  - Cell Movement
MH  - Cell Survival
MH  - Dental Pulp/*cytology
MH  - Diabetes Mellitus, Experimental/*therapy
MH  - Diabetes Mellitus, Type 1/*therapy
MH  - Disease Models, Animal
MH  - Glucose Transporter Type 2/metabolism
MH  - Homeodomain Proteins/metabolism
MH  - Humans
MH  - Ki-67 Antigen/metabolism
MH  - Male
MH  - Nerve Tissue Proteins/metabolism
MH  - Paired Box Transcription Factors/metabolism
MH  - Pancreas/cytology/metabolism/*physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Regeneration
MH  - *Stem Cell Transplantation
MH  - Stem Cells/*physiology
MH  - Streptozocin
OTO - NOTNLM
OT  - Human dental pulp stem cells
OT  - Rat
OT  - Streptozotocin
OT  - Transplantation
OT  - Type 1 diabetes mellitus
EDAT- 2020/06/02 06:00
MHDA- 2020/09/25 06:00
CRDT- 2020/06/02 06:00
PHST- 2020/01/09 00:00 [received]
PHST- 2020/05/20 00:00 [accepted]
PHST- 2020/06/02 06:00 [pubmed]
PHST- 2020/09/25 06:00 [medline]
PHST- 2020/06/02 06:00 [entrez]
AID - 10.1007/s12565-020-00550-2 [pii]
AID - 10.1007/s12565-020-00550-2 [doi]
PST - ppublish
SO  - Anat Sci Int. 2020 Sep;95(4):523-539. doi: 10.1007/s12565-020-00550-2. Epub 2020 
      May 31.