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. 2012 Dec 27;18(1):75–88. doi: 10.2478/s11658-012-0040-5

Differentiation of mesenchymal stem cells derived from human bone marrow and subcutaneous adipose tissue into pancreatic islet-like clusters in vitro

Dhanasekaran Marappagounder 1,✉, Indumathi Somasundaram 2, Sudarsanam Dorairaj 2, Rajkumar Janavikula Sankaran 1
PMCID: PMC6275636  PMID: 23271432

Abstract

Although stem cells are present in various adult tissues and body fluids, bone marrow has been the most popular source of stem cells for treatment of a wide range of diseases. Recent results for stem cells from adipose tissue have put it in a position to compete for being the leading therapeutic source. The major advantage of these stem cells over their counterparts is their amazing proliferative and differentiation potency. However, their pancreatic lineage transdifferentiation competence was not compared to that for bone marrow-derived stem cells. This study aims to identify an efficient source for transdifferentiation into pancreatic islet-like clusters, which would increase potential application in curative diabetic therapy. The results reveal that mesenchymal stem cells (MSC) derived from bone marrow and subcutaneous adipose tissue can differentiate into pancreatic islet-like clusters, as evidenced by their islet-like morphology, positive dithizone staining and expression of genes such as Nestin, PDX1, Isl 1, Ngn 3, Pax 4 and Insulin. The pancreatic lineage differentiation was further corroborated by positive results in the glucose challenge assay. However, the results indicate that bone marrow-derived MSCs are superior to those from subcutaneous adipose tissue in terms of differentiation into pancreatic islet-like clusters. In conclusion, bone marrow-derived MSC might serve as a better alternative in the treatment of diabetes mellitus than those from adipose tissue.

Key words: Diabetes, Islet-like clusters, Bone marrow, Subcutaneous fat, Mesenchymal stem cells, Transdifferentiation, Flow cytometry, Intracellular staining, Dithizone staining, Glucose challenge assay

Full Text

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Abbreviations used

ADSC

adipose-derived stem cells

APC

allophycocyanin

BD-FACS

Becton Dickinson-fluorescent activated cell sorting

BM

bone marrow

BMSC

bone marrow-derived stem cells

CD

cluster of differentiation

Cy

cyanine

DMEM-LG

Dulbecco’s modified eagle medium - low glucose

DPBS

Dulbecco’s phosphate buffer saline

DTZ

dithizone

ECM

extracellular matrix

EDTA

ethylene diamine tetra acetic acid

FBS

fetal bovine serum

FITC

fluorescein isothiocyanate

IDT

integrated DNA technologies

HLA-DR

human leukocyte antigen-DR

Isl 1

islet 1

MSC

mesenchymal stem cells

Ngn 3

neurogenin 3

Pax 4

paired box gene 4

PDX 1

pancreatic duodenal homeobox 1

PE

phyco erythrin

PER-CP

peridininchlorophyll-protein-complex

SVF

stromal vascular fraction

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