The co-transplantation of bone marrow derived mesenchymal stem cells reduced inflammation in intramuscular islet transplantation.

Abstract

AIMS/HYPOTHESIS:

Although the muscle is one of the preferable transplant sites in islet transplantation, its transplant efficacy is poor. Here we attempted to determine whether an intramuscular co-transplantation of mesenchymal stem cells (MSCs) could improve the outcome.

METHODS:

We co-cultured murine islets with MSCs and then analyzed the morphological changes, viability, insulin-releasing function (represented by the stimulation index), and gene expression of the islets. We also transplanted 500 islets intramuscularly with or without 5 × 105 MSCs to diabetic mice and measured their blood glucose level, the glucose changes in an intraperitoneal glucose tolerance test, and the plasma IL-6 level. Inflammation, apoptosis, and neovascularization in the transplantation site were evaluated histologically.

RESULTS:

The destruction of islets tended to be prevented by co-culture with MSCs. The stimulation index was significantly higher in islets co-cultured with MSCs (1.78 ± 0.59 vs. 7.08 ± 2.53; p = 0.0025). In terms of gene expression, Sult1c2, Gstm1, and Rab37 were significantly upregulated in islets co-cultured with MSCs. Although MSCs were effective in the in vitro assays, they were only partially effective in facilitating intramuscular islet transplantation. Co-transplanted MSCs prevented an early inflammatory reaction from the islets (plasma IL-6; p = 0.0002, neutrophil infiltration; p = 0.016 inflammatory area; p = 0.021), but could not promote neovascularization in the muscle, resulting in the failure of many intramuscular transplanted islets to engraft.

CONCLUSIONS:

In conclusion, co-culturing and co-transplanting MSCs is potentially useful in islet transplantation, especially in terms of anti-inflammation, but further augmentation for an anti-apoptosis effect and neovascularization is necessary.

• Authors: Gumpei Yoshimatsu, Naoaki Sakata, Haruyuki Tsuchiya, Takashi Minowa, Taro Takemura, Hiromi Morita, Tatsuo Hata, Masahiko Fukase, Takeshi Aoki, Masaharu Ishida, Fuyuhiko Motoi, Takeshi Naitoh, Yu Katayose, Shinichi Egawa, Michiaki Unno
• Journal: PloS one (PLoS One) Vol. 10 Issue 2 Pg. e0117561 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 25679812 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Topics

• Animals
• Apoptosis (genetics)
• Cell Culture Techniques
• Coculture Techniques
• Diabetes Mellitus, Experimental
• Disease Models, Animal
• Gene Expression Profiling
• Gene Expression Regulation
• Inflammation (etiology, pathology, therapy)
• Islets of Langerhans (metabolism)
• Islets of Langerhans Transplantation (adverse effects)
• Male
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells (cytology)
• Mice
• Neovascularization, Physiologic