Mesenchymal Stem Cells (MSCs): A Novel Therapy for Type 2 Diabetes

Figure 1

(a) Possible mechanisms of action for MSCs to promote islet regeneration. MSCs might initiate endogenous insulin production and stimulate the proliferation of β-cells. Various bioactive molecules secreted by MSCs, such as VEGF, TGF-β, and IL-6, can lead to enhanced vascularization and islet function. Besides, mitochondria of MSCs could be transferred to β-cells under hypoxia conditions to enhance the insulin secretion rate. MSCs show their antiapoptotic effect by downregulating ROS, caspase 3, caspase 8, and p53 and upregulating Bcl2. MSCs are capable of enhancing the formation of phagosomes, leading to the improved clearance of impaired mitochondria and the increased number of insulin granules. (b) Possible mechanisms of action for MSCs to influence hepatic metabolic homeostasis. MSCs can reduce the number of impaired mitochondria and systemic ROS levels to prevent liver metabolic imbalance. Upon MSC administration, PPAR-α was upregulated while PPAR-γ was downregulated. The expression of enzymes involved in hepatic glycolysis (GCK, L-PK, and PFK) is elevated, while the enzymes involved in gluconeogenesis (PGC-1α, PEPCK, and G6Pase) are reduced. In addition, MSCs can activate AKT and AMPK signaling pathways, which play a key role in cell metabolism. MSCs could significantly lower disordered biochemical markers of liver function caused by HFD, for instance, AKP, LDH, ALT, and AST, as well as reduce hepatic lipid accumulation and ameliorate insulin sensitivity. Abbreviations: VEGF: vascular endothelial growth factor; TGF-β: transforming growth factor-β; IL-1Ra: interleukin-1 receptor agonist; ER: endoplasmic reticulum; ROS: reactive oxygen species; AKT: protein kinase B; AMPK: AMP-activated protein kinase; HFD: high-fat diet; GCK: glucokinase; L-PK: liver pyruvate kinase; PFK: 6-phosphofructo-1-kinase; PGC-1α: peroxisome proliferator γ-activated receptor coactivator 1-α; PEPCK: phosphoenolpyruvate carboxykinase; G6Pase: glucose-6-phosphatase; AKP: alkaline phosphatase; LDH: lactate dehydrogenase; ALT: alanine aminotransferase; AST: aspartate aminotransferase.