Nicotinamide Facilitates Mesenchymal Stem Cell Differentiation Into Insulin-Producing Cells and Homing to Pancreas in Diabetic Mice.

Abstract

OBJECTIVE:

This study aimed to investigate the effect of nicotinamide on differentiation of mesenchymal stem cells (MSCs) into insulin-producing cells (IPCs) in vivo in mice and on homing of MSCs to the pancreas after being intravenously infused.

METHODS:

Streptozotocin (STZ)-induced diabetic Balb/c mice received syngeneic transplantation of carboxyfluorescein succinimidyl ester (CFSE)-labeled bone marrow MSCs into the liver or tail vein. Nicotinamide was intraperitoneally injected into mice at a dose of 500 mg/kg body weight per day after STZ administration. Mice who received saline solution injection instead of nicotinamide were involved as control.

RESULTS:

Mice that received nicotinamide injection showed lower blood glucose, higher serum insulin, and more improved glucose tolerance compared with the control group. Immunohistochemistry analysis showed that higher levels of insulin staining and higher percentages of CFSE+/insulin+ cells were observed in the liver and pancreas sections of mice who received nicotinamide injection compared with the control group. The percentage of CFSE+/insulin+ cells was positively correlated with serum insulin level. Real-time polymerase chain reaction results showed that the implanted MSCs in mice who received nicotinamide injection exhibited higher levels of β-cell-related gene expression than the control group. More CFSE-labeled MSCs appeared in the pancreas of mice who received nicotinamide injection compared with the control group after being intravenously infused, whereas the amount of CFSE-labeled MSCs in the liver was not affected by nicotinamide injection.

CONCLUSIONS:

Nicotinamide facilitates MSCs differentiating into functional IPCs in vivo in diabetic mice and promotes intravenously infused MSCs to home to the pancreas.