Regenerative Therapy

Regenerative Therapy

Volume 16, March 2021, Pages 42-52
Regenerative Therapy

Original Article
Subcutaneous transplantation of engineered islet/adipose-derived mesenchymal stem cell sheets in diabetic pigs with total pancreatectomy

https://doi.org/10.1016/j.reth.2020.12.005Get rights and content
Under a Creative Commons license
open access

Highlights

  • The adipose-derived mesenchymal stem cell sheet is useful to protect the islets.

  • Subcutaneous islet transplantation on sheet normalized blood glucose in diabetic pig.

  • Subcutaneous islet transplantation on sheet can be a useful tool.

Abstract

Introduction

Intraportal islet transplantation is a promising therapeutic approach for patients with type 1 diabetes mellitus (T1DM). However, despite being minimally invasive, the method has some limitations, such as short-term graft loss, portal venous thrombosis, and difficulty in collecting adequate amounts of islets. Subcutaneous islet transplantation on adipose-derived mesenchymal stem cell (ADSC) sheets has been suggested to overcome these limitations, and in this study, we have examined its feasibility in T1DM pigs.

Methods

Inguinal subcutaneous fat was harvested from young pigs and then isolated and cultured adequate ADSCs to prepare sheets. Islets were isolated from the pancreases of mature pigs and seeded on the ADSC sheets. T1DM pigs were generated by total pancreatectomy, and ADSC sheets with transplanted islets were administered subcutaneously to the waist (n = 2). The effects of the islets on the ADSC sheets and on blood glucose levels were evaluated. Insulin secretion was measured by insulin stimulation index.

Results

Islet viability was higher on ADSCs compared to islets alone (91.8 ± 4.3 vs. 81.7 ± 4.1%). The insulin stimulation index revealed higher glucose sensitivity of islets on ADSC sheets compared to islets alone (2.8 ± 2.0 vs. 0.8 ± 0.3). After transplantation, the blood glucose levels of two pigs were within the normal range, and sensitive insulin secretion was confirmed by intravenous glucose tolerance tests. After graftectomy, decreased insulin secretion and hyperglycemia were observed.

Conclusions

Subcutaneous islet transplantation using ADSC sheets can regulate the blood glucose levels of T1DM pigs.

Keywords

Islet transplantation
Adipose-derived mesenchymal stem cells
Subcutaneous
Pig
Type 1 diabetes mellitus

Abbreviations

T1DM
Type 1 diabetes mellitus
IBMIR
instant blood-mediated inflammatory reaction
MSC
mesenchymal stem cell
ADSC
adipose-derived mesenchymal stem cell
PBS
phosphate-buffered saline
DMEM
Dulbecco's modified Eagle's medium
FBS
fetal bovine serum
UW
University of Wisconsin
MEM
minimum essential medium
IEQ
islet equivalent
H & E
hematoxylin and eosin
ELISA
enzyme-linked immunosorbent assay
CGM
continuous glucose monitor
IVGTT
intravenous glucose tolerance test
SD
standard deviation
TGF
transforming growth factor
HGF
hepatocyte growth factor
HSP32
heat shock protein 32
XIAP
X-linked inhibitor of apoptosis protein

Cited by (0)

Peer review under responsibility of the Japanese Society for Regenerative Medicine.