Lab Anim Res.  2011 Jun;27(2):171-176. 10.5625/lar.2011.27.2.171.

Bone Marrow-Derived Mesenchymal Stem Cells Improve the Functioning of Neurotrophic Factors in a Mouse Model of Diabetic Neuropathy

• Kim BJ
• Jin HK
• Bae JS

• KMID: 2053667
• DOI: http://doi.org/10.5625/lar.2011.27.2.171

Abstract

Diabetic neuropathy is one of the most frequent and troublesome complications of diabetes. Although there has been a continuous increase in the incidence of diabetic neuropathy, treatments have yet to be found that effectively treat diabetic neuropathy. Neurotrophic factors are proteins that promote the survival of specific neuronal populations. They also play key roles in the regeneration of peripheral nervous system. Recent evidence from diabetic animal models and human diabetic subjects suggest that reduced availability of neurotrophic factors may contribute to the pathogenesis of diabetic neuropathy. One way to reverse this effect is to take advantage of the finding that bone marrow derived mesenchymal stem cells (BM-MSCs) promote peripheral nerve repair and the functioning of neurotrophic factors. Therefore, we speculated that treatment with BM-MSCs could be a viable therapeutic strategy for diabetic neuropathy. The present study was designed to examine the possible beneficial effect of BM-MSCs on functions of neurotrophic factors in diabetic neuropathy. To assess this possibility, we used an in vivo streptozotocin-induced diabetic neuropathy mouse model. Quantitative real-time polymerase-chain reacion showed that BM-MSCs significantly increase expression levels of neurotrophic factors. Also, BM-MSCs ameliorated nerve conduction velocity in streptozotocin-treated mice. These results may help to elucidate the mechanism by which BM-MSCs function as a cell therapy agent in diabetic neuropathy.

Keyword

Diabetic neuropathy; bone marrow-derived mesenchymal stem cells (BM-MSCs); neurotrophic factors

MeSH Terms

Animals
Bone Marrow
Diabetic Neuropathies
Humans
Imidazoles
Incidence
Mesenchymal Stromal Cells
Mice
Models, Animal
Nerve Growth Factors
Neural Conduction
Neurons
Nitro Compounds
Peripheral Nerves
Peripheral Nervous System
Proteins
Regeneration
Tissue Therapy
Imidazoles
Nerve Growth Factors
Nitro Compounds
Proteins

Figure

• 

  Figure 1 Bone marrow-derived mesenchymal stem cells (BM-MSCs) transplantation improved sciatic motor nerve conduction velocity (MNCV) in mice with diabetic neuropathy (DN). (A) 12 weeks after streptozotocin treatment, sciatic MNCV was significantly delayed in streptozotocin-treated mice compared with normal mice (n=10 per group). After measurement of sciatic MNCV, BM-MSCs were transplanted into the muscles percutaneously along the course of the sciatic nerve. (B) 2 weeks after BM-MSC transplantation, a significant improvement of sciatic MNCV occurred in BM-MSCs injected diabetic mice (n=5 per group). (C) 4 weeks after BM-MSCs transplantation, there were no significant differences in sciatic MNCV between any of the diabetic mice groups (n=5 per group). Data represent mean±SEM. Independent t-test, one-way ANOVA, *P<0.05 vs. normal mice; †P<0.05 vs. diabetic mice treated with phosphate-buffered saline (PBS).

• 

  Figure 2 Bone marrow-derived mesenchymal stem cells (BM-MSCs) transplantation increased expression levels of neurotrophic factors (NTFs) in mice with diabetic neuropathy (DN). The mRNA expression levels of NTFs in sciatic nerve and muscle were measured by quantitative real-time polymerase-chain reaction. (A) Two weeks after BM-MSCs transplantation, significant improvement of expression levels of NTFs observed in the BM-MSCs injected diabetic mice (n=5 per group). (B) Four weeks after BM-MSC transplantation, there was no significant difference in expression of NTFs between any of the diabetic mice groups (n=5 per group). Data represent mean±SEM. Independent t-test, one-way ANOVA, *P<0.05 vs. normal mice; †P<0.05 vs. diabetic mice treated with phosphate-buffered saline (PBS).

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