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Open Access Research article

Restoration of angiogenic capacity of diabetes-insulted mesenchymal stem cells by oxytocin

Yong Sook Kim12, Jin Sook Kwon1, Moon Hwa Hong2, Wan Seok Kang2, Hye-yun Jeong2, Hye-jin Kang2, Myung Ho Jeong13 and Youngkeun Ahn123*

Author Affiliations

1 Heart Research Center, Chonnam National University Hospital, 42 Jebong-Ro, Dong-Gu, Gwangju 501-757, South Korea

2 Research Laboratory of Cardiovascular Regeneration, Chonnam National University Hospital, 42 Jebong-Ro, Dong-Gu, Gwangju 501-757, South Korea

3 Department of Cardiology, Chonnam National University Hospital, 42 Jebong-Ro, Dong-Gu, Gwangju 501-757, South Korea

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BMC Cell Biology 2013, 14:38  doi:10.1186/1471-2121-14-38

Published: 11 September 2013

Abstract

Background

Angiogenesis is the main therapeutic mechanism of cell therapy for cardiovascular diseases, but diabetes is reported to reduce the function and number of progenitor cells. Therefore, we studied the effect of streptozotocin-induced diabetes on the bone marrow-mesenchymal stem cell (MSC) function, and examined whether diabetes-impaired MSC could be rescued by pretreatment with oxytocin.

Results

MSCs were isolated and cultured from diabetic (DM) or non-diabetic (non-DM) rat, and proliferation rate was compared. DM-MSC was pretreated with oxytocin and compared with non-DM-MSC. Angiogenic capacity was estimated by tube formation and Matrigel plug assay, and therapeutic efficacy was studied in rat myocardial infarction (MI) model.

The proliferation and angiogenic activity of DM-MSC were severely impaired but significantly improved by pretreatment with oxytocin. Krüppel-like factor 2 (KLF2), a critical angiogenic factor, was dramatically reduced in DM-MSC and significantly restored by oxytocin. In the Matrigel plug assay, vessel formation of DM-BMSCs was attenuated but was recovered by oxytocin. In rat MI model, DM-MSC injection did not ameliorate cardiac injury, whereas oxytocin-pretreated DM-MSC improved cardiac function and reduced fibrosis.

Conclusions

Our results show that diabetes influenced MSC by reducing angiogenic capacity and therapeutic potential. We demonstrate the striking effect of oxytocin on stem cell dysfunction and suggest the use of oxytocin as a priming reagent in autologous stem cell therapy.

Keywords:
Diabetes; Angiogenesis; Stem cells; Oxytocin; Krüppel-like factor 2