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Stem Cells: Biology and Engineering pp 145–156Cite as

Intravenous Infusion of Human Adipose Tissue-Derived Mesenchymal Stem Cells to Treat Type 1 Diabetic Mellitus in Mice: An Evaluation of Grafted Cell Doses

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Part of the book series: Advances in Experimental Medicine and Biology ((ICRRM,volume 1083))

Abstract

Mesenchymal stem cell (MSC) transplantation is a novel treatment for diabetes mellitus, especially type 1 diabetes. Many recent publications have demonstrated the efficacy of MSC transplantation on reducing blood glucose and increasing insulin production in both preclinical and clinical trials. However, the investigation of grafted cell doses has been lacking. Therefore, this study aimed to evaluate the different doses of MSCs on treatment of type 1 diabetes in mouse models. MSCs were isolated and expanded from human adipose tissue. Streptozotocin (STZ)-induced diabetic mice were divided into two groups that were intravenously transfused with two different doses of human MSCs: 106 or 2.106 cells/mouse. After transplantation, both grafted and placebo mice were monitored weekly for their blood glucose levels, glucose and insulin tolerance, pancreatic structural changes, and insulin production for 56 days after transplantation. The results showed that the higher dose of MSCs (2.106 cells/mouse) remarkably reduced death rate. The death rates were 50%, 66%, and 0% in placebo group, low-dose (1.106 MSCs) group, and high-dose (2.106 MSCs) group, respectively, after 56 days of treatment. Moreover, blood glucose levels were lower for the high-dose group compared to other groups. Glucose and insulin tolerance, as well as insulin production, were significantly improved in mice transplanted with 2.106 cells. The histochemical analyses also support these results. Thus, a higher (e.g., 2.106) dose of MSCs may be an effective dose for treatment of type 1 diabetes mellitus.

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Abbreviations

hADSCs:

Human adipose-derived stem cells

GTT:

Glucose tolerance test

H&E:

Hematoxylin and eosin

MSCs:

Mesenchymal stem cells

STZ:

Streptozotocin

Th1/Th2:

T helper 1/T helper 2

TNF-α:

Tumor necrosis factor-alpha

IL-10:

Interleukin-10

IL-12:

Interleukin-12

IFN-γ:

Interferon-gamma

EGF:

Epidermal growth factor

bFGF:

Basic fibroblast growth factor

PDGF:

Platelet-derived growth factor

TGF-β:

Transforming growth factor-beta

VEGF:

Vascular endothelial growth factor

HGF:

Hepatocyte growth factor

IGF:

Insulin growth factor-1

NO:

Nitric oxide

PGE2:

Prostaglandin E2

IDO:

Indoleamine 2,3-dioxygenase

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Acknowledgment

This research was funded by the Ministry of Science and Technology via project Grant No. DTDL.2012-G/23 and Vietnam National University, Ho Chi Minh City, via project No. C2016-18-18.

Author Contribution

LTTD, designed the study, performed the experiments, analyzed the data, and drafted the manuscript; PVP, KDT, designed the study and reviewed and corrected the manuscript; ANTB, CLTN, performed the experiments and analyzed the data and drafted the manuscript; NCT, ATVB, performed the experiments and reviewed and drafted the manuscript; and NPK analyzed the data and wrote the manuscript.

Competing Interests

The authors declare that no competing interests exist.

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Authors and Affiliations

  1. Stem Cell Institute, University of Science, VNUHCM, Ho Chi Minh city, Vietnam

    Loan Thi-Tung Dang, Anh Nguyen-Tu Bui, Cong Le-Thanh Nguyen, Nhat Chau Truong, Anh Thi-Van Bui, Ngoc Phan Kim & Phuc Van Pham

  2. Laboratory of Stem Cell Research and Application, University of Science, VNUHCM, Ho Chi Minh city, Vietnam

    Cong Le-Thanh Nguyen, Nhat Chau Truong, Anh Thi-Van Bui & Phuc Van Pham

  3. Medical Genetics Institute, Ho Chi Minh city, Vietnam

    Kiet Dinh Truong

Authors
  1. Loan Thi-Tung Dang
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  2. Anh Nguyen-Tu Bui
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  3. Cong Le-Thanh Nguyen
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  4. Nhat Chau Truong
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  6. Ngoc Phan Kim
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  7. Kiet Dinh Truong
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  8. Phuc Van Pham
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Correspondence to Phuc Van Pham .

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  1. Laboratory of Stem Cell Research and Application, University of Science, Vietnam National University, Ho Chi Minh City, Vietnam

    Phuc Van Pham

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Dang, L.TT. et al. (2017). Intravenous Infusion of Human Adipose Tissue-Derived Mesenchymal Stem Cells to Treat Type 1 Diabetic Mellitus in Mice: An Evaluation of Grafted Cell Doses. In: Van Pham, P. (eds) Stem Cells: Biology and Engineering. Advances in Experimental Medicine and Biology(), vol 1083. Springer, Cham. https://doi.org/10.1007/5584_2017_127

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