Abstract
The present study was carried out to investigate and compare the in vitro differentiation potential of mesenchymal stem cells (MSCs) isolated from human dental tissues (pulp, papilla, and follicle) of the same donor. MSCs were isolated from dental tissues (pulp, papilla, and follicle) following digestion method and were analyzed for the expression of pluripotent markers and cell surface markers. All three types of MSCs were evaluated for their potential to differentiate into mesenchymal lineages. Further, the MSCs were differentiated into pancreatic β cell-like cells using multistep protocol and characterized for the expression of pancreatic lineage specific markers. Functional properties of differentiated pancreatic β cell-like cells were assessed by dithizone staining and glucose challenge test. All three types of MSCs showed fibroblast-like morphology upon culture and expressed pluripotent, and mesenchymal cell surface markers. These MSCs were successfully differentiated into mesenchymal lineages and transdifferentiated into pancreatic β cell-like cells. Among them, dental follicle derived MSCs exhibits higher transdifferentiation potency toward pancreatic lineage as evaluated by the expression of pancreatic lineage specific markers both at mRNA and protein level, and secreted higher insulin upon glucose challenge. Additionally, follicle-derived MSCs showed higher dithizone staining upon differentiation. All three types of MSCs from a single donor possess similar cellular properties and can differentiate into pancreatic lineage. However, dental follicle derived MSCs showed higher potency toward pancreatic lineage than pulp and papilla derived MSCs, suggesting their potential application in future stem cell based therapy for the treatment of diabetes.
Highlights
Diabetes mellitus (DM) is one of the devastating disease characterized either by absolute insulin deficiency due to the destruction of β cells (Type 1) or by relative insulin deficiency due to the reduced insulin sensitivity in peripheral cells (Type 2) [1]
The mesenchymal stem cells (MSCs) isolated from human dental pulp, papilla, and follicle tissues exhibited adherent fibroblast like spindle morphology that become homogeneous at passage 3 upon sub culturing (Figure 1)
Mesenchymal stem cells isolated from dental pulp, papilla, and follicle tissues exhibited largely similar features related to morphology, proliferation, expression of various cell surface, intracellular and pluripotent markers, and differentiation toward mesenchymal lineages such as osteocytes, adipocytes, and chondrocytes
Summary
Diabetes mellitus (DM) is one of the devastating disease characterized either by absolute insulin deficiency due to the destruction of β cells (Type 1) or by relative insulin deficiency due to the reduced insulin sensitivity in peripheral cells (Type 2) [1]. DM results in abnormal plasma glucose level and the long-term hyperglycemia can cause severe complications such as diabetic nephropathy, diabetic retinopathy, cardiovascular disease, cataract, and neuropathy [2,3]. The exogenous insulin replacement is considered as a primary therapeutic approach to control plasma glucose levels. It does not match the precision of functioning β cells [4], and it imposes psychological, physical, and financial burden on patients [5]. Even short- and long-acting, genetically synthesized insulin fails to match the sensitivity of nutrient induced endogenous insulin production, resulting in undesirable outcomes [3].
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