Review Article

Mesenchymal Stem Cells: An Excellent Candidate for the Treatment of Diabetes Mellitus

Table 1

Protocols that induce MSCs into IPCs.

Cell sourceInduce MSCs into IPCsTransplantation way and results

Rat BM-MSCs [26]Stage 1, 6 days: 10 ng/ml bFGF, 10 ng/ml EGF, 2% B27Transplantation way: injected into intraperitoneal
Stage 2, 6 days: 10 ng/ml HGF, 10 ng/ml b-cellulin, 10 ng/ml AA, 10 mmol/L NA, 2% B27Results: IPC transplantation improved insulin level better than MSC transplantation

Human BM-MSCs [24];Stage 1, 3 days: 55 nmol/L TSA, serum-free DMEMTransplantation way: cells were loaded in 2 TheraCyte capsules and transplanted under the rectus sheath

Mice BM-MSCs [28]Stage 2, 7 days:10 nmol/L GLP-1, 10% FBS, DMEM : DMEM/F12Results: the transplanted cells were glucose-responsive and insulin-secreting. Four weeks after transplantation, blood sugar values became normal

Rat AD-MSCs [29]Stage 1, 2 days: 10 mmol/l NA, 0.5 mmol/l β-mercaptoethanol and serum-free high-glucose DMEM (25 mmol/l)Transplantation way: transplanted into the distal tip of the spleen
Stage 2, 26 days: 30 ng/ml FGF, 10 mmol/l NA and serum-free high-glucose DMEM (25 mmol/l)Results: IPC transplantation significantly reduced the glucose level. And IPCs were indeed responsive to a glucose challenge in vivo

Human UC-MSCs [30]Stage 1, 7 days: CMRL1066 medium containing 10% FBS, 1% PSA, 100 ng/ml of β-nerve growth factor, 4 nM AA, 10 mM NA, and 25 ng/ml EGFTransplantation way: injected through a retroorbital vein
Stage 2, 7–10 days: the culture medium was changed to DMEM/F12, and the other components were the same as those in stage 1Results: IPC transplantation decreased blood glucose, improved glucose tolerance, increased body weight, and prolonged the survival time of NOD mice. And IPCs containing human C-peptide and human nuclei were located in the liver
Stage 3, 17 days: 10 mM NA, ITS, and 10 ng/ml bFGF

Human BM-MSCs [23]Stage 1, 2 days: serum-free, glucose-rich DMEM (25 mmol/L) containing 0.5 mmol/L β-mercaptoethanolTransplantation way: inserted under the renal capsule
Stage 2, 8 days: serum-free, glucose-rich medium containing 1% nonessential amino acids, 20 ng/ml bFGF, 20 ng/ml EGF, 2% B27 supplement, and 2 mmol/L L-glutamineResults: IPC treatment resulted in control of nude diabetic mice diabetic status for 3 months
Stage 3, 8 days: serum free, glucose-rich DMEM containing 10 ng/ml betacellulin, 10 ng/ml AA, 2% B27 supplement, and 10 mmol/L NA

Human BM-MSCs [31]Stage 1, 3 days: DMEM, 55 nmol/L TSATransplantation way: implanted beneath the renal capsule
Stage 2, 7 days: high-glucose (25 mmol/L) medium containing a 1 : 1 ratio of DMEM : DMEM/F12, 10% FBS, and 10 nmol/L GLP-1Results: diabetic mice became euglycemic 8 ± 3 days after transplantation. The results of the oral glucose tolerance test were normal

Rat BM-MSCs [32]Stage 1, 2 days: DMEM low-glucose medium containing 10 mmol/L NA,0.5 mmol/L
2-mercaptoethanol, and 5% FBS
Transplantation way: injected via tail veins
Stage 2, 24 hours: serum-free DMEM high-glucose medium containing 0.5 mol/L
2-mercaptoethanol, 10 mmol/L NA, 5% FBS, and10 ng/Ml AA
Results: IPC therapy significantly improved the body weight and serum insulin, alpha-amylase, adiponectin, creatinine, total cholesterol, triacylglycerol, IL-6, TNF-α, liver L-malonaldehyde, and glycogen levels in the STZ-induced diabetes model
Stage 3, 8 days: DMEM-HG medium containing 20 ng/mL bFGF, 20 ng/mL EGF, 2 mmol/L L-glutamine, 5% FBS, and10 mmol/L NA

Human UC-MSCs [33]Stage 1, 2 days: DMEM/F12 (1 : 1) with 17.5 mM glucose, 1% fatty acid-free BSA Cohn fraction V, 4 nM AA, 1% PSA, 1× ITS-X (ITS-X; 5 mg/L insulin, 5 mg/L transferrin, and 5 mg/L selenium), and 50 μM 2-mercaptoethanolTransplantation way: injected via the portal vein
Stage 2, 2 days: DMEM/F12 (1 : 1) with 17.5 mM glucose, 1% BSA, 1% PSA, ITS-X, and 0.3 mM taurineResults: IPC treatment increased serum insulin and C-peptide level and improved glucose tolerance
Stage 3, 6 days: DMEM/F12 (1 : 1) with 17.5 mM glucose, 1.5% BSA, ITS-X, 1% PSA, 3 mM taurine, 100 nM GLP-1, 1 mM NA, and 1× nonessential amino acids

VG : vildagliptin, bFGF: basic fibroblast growth factor, HGF: hepatocyte growth factor, EGF: epidermal growth factor, AA: activin A, NA: nicotinamide, TSA: trichostatin A, DMEM: Dulbecco’s Modified Eagle’s Medium, GLP-1: glucagon-like peptide 1, FBS: fetal bovine serum, ITS: insulin transferrin selenium, and PSA: penicillin/streptomycin/amphoteric B.