Efficient generation of functional pancreatic β cells from dental-derived stem cells via laminin-induced differentiation

Abstract

Background This study was designed to generate functional insulin-producing cells (IPCs) from dental-derived mesenchymal stem cells (MSCs) and further explore their therapeutic potential against diabetes mellitus in vivo. MSCs were isolated from human dental pulp and periodontal ligament and were induced to differentiate into insulin-producing cells (IPCs) using laminin-based differentiation protocol for 14 days. Confirmation of IPCs was performed through real-time PCR analysis and insulin release assay. Then, the generated IPCs were labeled with PKH26 dye prior to transplantation in experimental animals. Twenty-eight days later, blood glucose, serum insulin (INS), c-peptide (CP), and visfatin (VF) levels and pancreatic glucagon (GC) level were estimated. Pancreatic forkhead box protein A2 (Foxa2) and SRY-box transcription factor 17 (Sox17), insulin-like growth factor I (IGF-1), and fibroblast growth factor10 (FGF 10) gene expression levels were analyzed. Results Dental stem cells were successfully differentiated into IPCs that demonstrated increased expression of pancreatic endocrine genes. IPCs released insulin after being subjected to high levels of glucose. In vivo findings uncovered that the implanted IPCs triggered significant decrease in blood glucose, serum VF, and pancreatic GC levels with significant increase in serum INS and CP levels. Furthermore, the implanted IPCs provoked significant upregulation in the expression level of pancreatic genes. Histopathological description of the pancreas tissues revealed that transplantation of IPCs ameliorated the destabilization of pancreas tissue architecture. Conclusion This study demonstrates the significant role of the implantation of IPCs generated from dental-derived stem cells in treatment of diabetes mellitus.

Dental Stem Cell-Based Therapy for Glycemic Control and the Scope of Clinical Translation: A Systematic Review and Meta-Analysis

“…The descriptive analysis of included animal studies is presented in Table 1. Seven studies were conducted in Japan [13,[46][47][48][49][50][51][52][53][54]; four in China [9,14,[55][56][57]; three in Egypt [58][59][60][61]; two in India [17,62]; and one in Brazil [63]. Mental state of rats.…”

“…Streptozotocin (STZ) was used to induce T1DM in 14 studies [9,13,17,46,48,[50][51][52]54,58,[60][61][62][63]; T2DM was induced using a high-fat diet in 2 studies [14,55], while in 1 study, T2DM was induced in rats which were given a high-fat diet and then administered with STZ [57]. Spraque Dawley (SD) rats were used in six studies [13,46,52,57,58,61]; Goto-Kakizaki (GK) rats were used in two [14,55]; Wistar rats in two [17,60]; Fischer 344 rats (F344-NJcl-rnu/rnu) in one study [54]; four studies used C57BL/6 mice [9,50,51,63]; and two used Bagg Albino (BALB/c) mice [48,62]. In 1 study, female mice were used [63], whereas 16 studies used male rats or mice.…”

“…SHED were used in 6 studies [14,50,51,55,57,62], and human DPSCs (hDPSCs) were used in five [17,48,54,58,60]. In one study, MSCs from human gingiva (hGMSCs) were used [9], whereas in another, insulin-producing cells (IPCs) derived from human periodontal ligament stem cells (hPDLSCs) and hDPSCs were used [61]. Rat derived DPSCs (rDPSCs) were used in three studies [13,46,52]; one study used DPSCs derived from the incisors of mice (mDPSCs) [63].…”

“…Rodent derived DPSCs were from the same species as the animals used to study DSC effects, although autotransplantation was not performed in any study. Whole SCs were used in 14 studies [9,13,14,17,46,48,54,55,57,58,[60][61][62][63], and 3 used serum-free conditioned medium containing secretory factors of SHED (SHED-CM) [50,51] or DPSCs (DPSC-CM) [52].…”

“…Intravenous (IV) route was used to administer DSCs in seven studies [14,55,57,58,60,61,63], and intramuscular (IM) route was used in five [13,46,48,50,52]. In one study, IPCs obtained from SHED were transplanted subcutaneously [62], while in another [54], IPCs were placed under renal capsules of diabetic animals.…”