Mesenchymal Stem Cells Derived from Bone Marrow of Diabetic Patients Portrait Unique Markers Influenced by the Diabetic Microenvironment

Original Data

Rev Diabet Stud, 2009, 6(4):260-270

DOI 10.1900/RDS.2009.6.260

Mesenchymal Stem Cells Derived from Bone Marrow of Diabetic Patients Portrait Unique Markers Influenced by the Diabetic Microenvironment

Smruti M. Phadnis¹^,², Surendra M. Ghaskadbi², Anandwardhan A. Hardikar³, Ramesh R. Bhonde¹^,⁴

¹Tissue Engineering and Banking Laboratory, National Center for Cell Science, Ganeshkhind Road, Pune MH 411007, India
²Division of Animal Sciences, Agharkar Research Institute, Agarkar Road, Pune, MH 411004, India
³Stem Cells and Diabetes Section, National Center for Cell Science, Ganeshkhind Road, Pune MH 411007, India
⁴Stempeutics Research Pvt. Ltd., 9th Floor, Manipal Hospital, HAL Airport Road, Bangalore 560017, India
Address correspondence to: Ramesh R. Bhonde, e-mail: ramesh.bhonde@stempeutics.com

Manuscript submitted October 2, 2009; resubmitted December 5, 2009; accepted December 11, 2009.

Keywords: diabetes, beta-cell, stem cell, differentiation, bone marrow, NGN3, NKX6.1, PAX6

Abstract

Cellular microenvironment is known to play a critical role in the maintenance of human bone marrow-derived mesenchymal stem cells (BM-MSCs). It was uncertain whether BM-MSCs obtained from a 'diabetic milieu' (dBM-MSCs) offer the same regenerative potential as those obtained from healthy (non-diabetic) individuals (hBM-MSCs). To investigate the effect of diabetic microenvironment on human BM-MSCs, we isolated and characterized these cells from diabetic patients (dBM-MSCs). We found that dBM-MSCs expressed mesenchymal markers such as vimentin, smooth muscle actin, nestin, fibronectin, CD29, CD44, CD73, CD90, and CD105. These cells also exhibited multilineage differentiation potential, as evident from the generation of adipocytes, osteocytes, and chondrocytes when exposed to lineage specific differentiation media. Although the cells were similar to hBM-MSCs, 6% (3/54) of dBM-MSCs expressed proinsulin/C-peptide. Emanating from the diabetic microenvironmental milieu, we analyzed whether in vitro reprogramming could afford the maturation of the islet-like clusters (ICAs) derived from dBM-MSCs. Upon mimicking the diabetic hyperglycemic niche and the supplementation of fetal pancreatic extract, to differentiate dBM-MSCs into pancreatic lineage in vitro, we observed rapid differentiation and maturation of dBM-MSCs into islet-like cell aggregates. Thus, our study demonstrated that diabetic hyperglycemic microenvironmental milieu plays a major role in inducing the differentiation of human BM-MSCs in vivo and in vitro.

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